Diseases doi: 10.3390/diseases12030057
Authors: Ludovico Abenavoli
The global health emergency caused by the Coronavirus disease-19 (COVID-19) pandemic officially ended on 11 May 2023 [...]
]]>Diseases doi: 10.3390/diseases12030056
Authors: Vlad Barbos Bogdan Feciche Silviu Latcu Alexei Croitor Vlad Dema Razvan Bardan Flaviu Ionut Faur Tudor Mateescu Dorin Novacescu Gherle Bogdan Alin Adrian Cumpanas
This study presents a systematic review of the literature on individuals’ health-related quality of life (HRQoL) following radical cystectomy for muscle-invasive bladder cancer (MIBC), utilizing the Short Form-36 Health Survey (SF-36) as a primary assessment tool. The review was designed as an exhaustive literature search across three major databases including PubMed, Scopus, and Embase up to December 2023, using the PRISMA guidelines. The selection process refined 2281 identified articles down to 11 studies meeting our inclusion criteria. These studies encompassed a diverse demographic and clinical profile of 774 participants, with follow-up durations ranging from 3 to 130 months, thereby offering insights into both short-term and long-term HRQoL outcomes. The results highlighted significant alterations in individuals’ HRQoL across various domains post-radical cystectomy. Notably, the Physical Functioning (PF) and Bodily Pain (BP) domains generally scored higher, indicating a moderate to high perceived physical health status. However, the Role Physical (RP) and Role Emotional (RE) domains showed variability, reflecting the challenges in daily role fulfillment and emotional adjustment post-surgery. A marked variability in physical recovery was observed, with studies reporting significant differences in PF and RP scores between patient groups. The General Health (GH) and Vitality (VT) domains sometimes reflected perceived deteriorations, whereas the Mental Health (MH) scores suggested that many patients maintained or achieved high levels of well-being post-operatively. The conclusions drawn from this systematic review underscore the profound and multi-faceted impact of radical cystectomy on HRQoL, varying widely between studies, being influenced by geographic factors, surgical methods, and the time of evaluation. The findings emphasize the necessity for holistic patient care approaches that address both physical and emotional rehabilitation, aiming to improve HRQoL outcomes.
]]>Diseases doi: 10.3390/diseases12030055
Authors: Amani A. Alrehaili Amal F. Gharib Maha M. Bakhuraysah Afaf Alharthi Ohud Alsalmi Fouzeyyah Ali Alsaeedi Reem Ali Alhakami Kamilah Ali Alasmari Nuha Mohammed Wael H. Elsawy
Squamous cell carcinoma of the head and neck (HNSCC) is a globally prevalent form of cancer with significant morbidity and mortality rates. The present study examines the relationship of serum pro-inflammatory cytokines and leptin levels with the effectiveness of therapy in individuals with HNSCC and their potential role as biomarkers for treatment response and toxicity. Induction chemotherapy and concomitant chemoradiotherapy were evaluated for efficacy and safety in 52 individuals with HNSCC. Both response and toxicity were evaluated, and serum levels of pro-inflammatory cytokines Interlukin-1 beta (IL-1β), Interlukin-2 (IL-2), Interlukin-6 (IL-6), and Tumor Necrosis Factor-Alpha (TNF-α) and leptin were measured using enzyme-linked immunoassay before and after treatment. Before treatment, these measurements were made in comparison with a control group with 50 healthy people. The results showed that serum cytokines and leptin levels varied depending on the response to treatment, with patients who had a complete or partial response (PR) showing significant decreases in IL-1 β, IL-6, and TNF-α levels and significant increases in IL-2 and leptin levels after treatment, with an improvement in cachexia. These results imply that variations in serum pro-inflammatory cytokines and leptin levels are likely related to the therapeutic effectiveness in HNSCC and may act as biomarkers for treatment response.
]]>Diseases doi: 10.3390/diseases12030054
Authors: Leila Itani Massimo Pellegrini Dana Saadeddine Hanen Samouda Dima Kreidieh Hana Tannir Marwan El Ghoch
Slow gait speed is associated with poorer clinical outcomes and higher rates of functional limitation and mortality in older adults, especially when combined with overweight or obesity. Aging is also associated with nutritional deficits. The aim of our study was to assess the potential association between dietary practice and gait speed performance in community-dwelling older adults with overweight and obesity. Participants underwent body composition measurement with the Tanita MC-780MA Bioimpedance Analyzer (BIA). Dietary patterns were assessed with the Mini Nutritional Assessment (MNA) questionnaire, and a dietary adequacy (DA) score system was constructed. The four-meter gait speed test was performed in order to assess gait speed. Of 222 participants, aged 67.6 ± 6.6 years, with a body mass index (BMI) of 31.9 ± 4.5 kg/m2, 34.7% had reduced gait speed and lower DA compared to those with normal gait speed (2.99 ± 1.12 vs. 3.37 ± 1.07; p < 0.05). The DA score of participants with slower gait speed was more likely to fall below the median than that of participants with normal gait speed (70.1% vs. 51.7%; p < 0.05). Participants with slower gait speed were more likely to be nutritionally at risk of low DA (22.1% vs. 10.3%; p < 0.05). Logistic regression analysis, after adjustment for confounders, showed that the risk of having a slow gait speed was 75% lower among those with a higher DA score (OR = 0.25; 95% CI = 0.11–0.53). Older adults with overweight or obesity in community dwellings might need to be supported with nutritional interventions that can improve their gait speed.
]]>Diseases doi: 10.3390/diseases12030053
Authors: Lehel-Barna Lakatos Manuel Bolognese Mareike Österreich Laura Weichsel Martin Müller
Objectives: Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. Methods: Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [IQR 1; 6]) with assessment of dCA, 183 exhibited the diagnosis of HBP. dCA parameters’ gain and phase were determined by transfer function analysis of spontaneous oscillations of blood pressure and cerebral blood flow velocity. Results: Patients used beta-blockers (n = 76), calcium channel blockers (60), diuretics (77), angiotensin-converting enzyme inhibitors (59), or angiotensin-1 receptor blockers (79), mostly in various combinations of two or three drug classes. dCA parameters did not differ between the non-HBP and the different HBP medication groups. Multinomial ordinal logistic regression models revealed that the use of diuretics decreased the likelihood of a less severe stroke (odds ratio 0.691, 95% CI 0.493; 0.972; p = 0.01) and that beta-blockers decreased the likelihood of a better modified Rankin score at 3 months (odds ratio 0.981, 95% CI 0.970; 0.992; p = 0.009). Other independent factors associated with stroke outcome were penumbra and infarct volume, treatment with mechanical thrombectomy, and the initial National Institute of Health Stroke Scale score. Interpretation: In this cohort of ischemic minor to moderate stroke patients, pre-stroke antihypertensive treatment with diuretics was associated with a more severe neurological deficit on admission and pre-stroke treatment with beta-blockers with a poorer 3-month outcome. The antihypertensive drug class used pre-stroke did not impact dCA.
]]>Diseases doi: 10.3390/diseases12030052
Authors: Matteo Vassallo Roxane Fabre Laurene Lotte Sabrina Manni Christian Pradier
Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (ORadj) = 5.30, 95% confidence interval (CI): 1.47–22.19, p = 0.014] and ineffective initial empirical therapy [ORadj 5.54, 95% CI: 1.95–17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [ORadj 9.40, 95% CI: 1.70–62.14, p = 0.012], AE group [ORadj 5.89, 95% CI: 1.70–21.40, p = 0.006], and clinical instability or death [ORadj 4.71, 95% CI: 1.44–17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC.
]]>Diseases doi: 10.3390/diseases12030051
Authors: Alexandra Papoudou-Bai Epameinondas Koumpis Georgia Karpathiou Eleftheria Hatzimichael Panagiotis Kanavaros
GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely characterized so far in cHL tissues. In this single-center retrospective cohort study we analyzed the expression patterns of GATA3 alone and in combination with B, T, NK or macrophage-associated markers in 73 cases with newly diagnosed cHL and investigated for a possible correlation with clinical and laboratory parameters. Immunohistochemistry (single and double) was performed using GATA3 alone and in combination with CD20, CD3, CD56, CD68, CD30 or CD15. Clinical and laboratory parameters were collected and correlated with the expression of GATA 3. GATA3 nuclear expression was found in HRS cells in 39/73 (54%) cases of cHL. The Nodular Sclerosis (NS) subtype showed the highest positivity rate (35/56, 63%), followed by mixed cellularity (MC; 4/14, 29%) and lymphocyte rich (LR; 0/3). Double immunostainings showed that GATA3 was expressed by CD30+ or CD15+ HRS cells and a few CD3+ T-cells, whereas GATA3 expression was not detected in CD20, CD56 or CD68+ cells. GATA3-negative cHL was significantly associated with unfavorable prognostic factors such as older age at diagnosis and increased levels of serum β2-microglobulin. The heterogenous expression patterns of GATA3 in HRS cells that were observed in a substantial proportion of cHL, mainly in the NS subtype, further support the biological heterogeneity of cHL.
]]>Diseases doi: 10.3390/diseases12030049
Authors: Fajer M. AlKandari Hussein S. Mohamed Sayed A. Ahmed Basant Mahmoud Asmaa M. Mahmoud
Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1β and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities.
]]>Diseases doi: 10.3390/diseases12030050
Authors: John Dawi Aishvaryaa Shree Mohan Yura Misakyan Scarlet Affa Edgar Gonzalez Karim Hajjar David Nikoghosyan Sabrina Fardeheb Christopher Tuohino Vishwanath Venketaraman
Meningitis is an inflammatory condition affecting the meninges surrounding the brain and spinal cord. Meningitis can be triggered by various factors, including infectious agents like viruses and bacteria and non-infectious contributors such as cancer or head injuries. The impact of meningitis on the central nervous system involves disruptions in the blood–brain barrier, cellular infiltrations, and structural alterations. The clinical features that differentiate between tuberculous meningitis (TBM) and non-tuberculous meningitis (NTM) are discussed in this review and aid in accurate diagnosis. The intricate interplay of reactive oxygen species, ferroptosis, and reactive nitrogen species within the central nervous system reveals a promising field of research for innovative therapeutic strategies tailored to TBM. This review highlights the alternative treatments targeting oxidative stress-induced TBM and ferroptosis, providing potential avenues for intervention in the pathogenesis of this complex condition.
]]>Diseases doi: 10.3390/diseases12030048
Authors: Lucia Merlino Agnese Immacolata Volpicelli Franco Anglana Giulia D’Ovidio Mattia Dominoni Marianna Francesca Pasquali Barbara Gardella Paolo Inghirami Pietro Lippa Roberto Senatori
Background: Hemangiomas are aberrant proliferations of blood vessels and the most frequent benign pediatric soft tissue tumors. Although they are common, genital localization is rare. This study aimed to assist doctors in the diagnosis, management, and treatment of pediatric vulvovaginal hemangiomas by conducting a review of the literature. Methods: We conducted a literature review including papers published between August 2009 and May 2023. Results: While most hemangiomas are usually indolent and resolve with time, in some cases, especially cervicovaginal and uterine ones, they might present with severe symptoms like heavy bleeding and need further instrumental investigation for diagnosis, like CT or MRI. As for the treatment, many options are available, with medical therapy or expectant management being the first choice. Conclusions: Vulvovaginal pediatric hemangiomas are rare and require more research on how to detect and manage these lesions, especially the symptomatic and the psychologically impacting ones. For the time being, treatment should be personalized based on the patient’s situation and clinician’s expertise.
]]>Diseases doi: 10.3390/diseases12030047
Authors: Simona Laurino Sabino Russi Ludmila Carmen Omer Alberto D’Angelo Giovanni Bozza Giuseppina Gallucci Geppino Falco Giandomenico Roviello Anna Maria Bochicchio
The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for “extended” anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered.
]]>Diseases doi: 10.3390/diseases12030046
Authors: Mark Ayoub Julton Tomanguillo Carol Faris Nadeem Anwar Harleen Chela Ebubekir Daglilar
Background: SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2’s impact on decompensation in previously compensated cirrhotic patients. Methods: We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX’s deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. Results: Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. Conclusions: SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.
]]>Diseases doi: 10.3390/diseases12030045
Authors: Rafael Fagundes Melo Lucas Fornari Laurindo Katia Portero Sloan Lance Alan Sloan Adriano Cressoni Araújo Piero Bitelli Tereza Laís Menegucci Zutin Rodrigo Haber Mellen Luciano Junqueira Mellen Elen Landgraf Guiguer João Paulo Cera Albarossi Márcia Rocha Gabaldi Patricia Cincotto dos S. Bueno Jesselina Francisco dos Santos Haber Sandra Maria Barbalho Eduardo Federighi Baisi Chagas
The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading to negative repercussions on the control of cardiovascular risk. We aimed to investigate the distribution of lipid levels and the presence of dyslipidemia in children and adolescents with T1DM. A cross-sectional observational study was conducted with 81 individuals of both sexes (4–19 years) diagnosed with T1DM. Anthropometric and biochemical data were collected, in addition to data on physical activity level, sexual maturation stage, and insulin administration regimen. Lipid levels were categorized as normal, borderline, and elevated, and the presence of dyslipidemia was diagnosed by the presence of one or more altered lipid parameter. We noted a prevalence of dyslipidemia in 65.4% of the participants when considering borderline lipid values. Of those, 23.5% had one altered lipid level, and 42.0% had two or more. The main altered lipid levels were total cholesterol and triglycerides, followed by non-HDL-c. The main factor associated with the worsening of lipid levels was the increase in HbA1c. Sex had a significant effect on the levels of TC, HDL-c, and ApoA-I. The results of this study reinforce the need to monitor lipid profile in children and adolescents with T1DM, as well as the importance of early intervention in treating dyslipidemia, especially in patients with poor glycemic control.
]]>Diseases doi: 10.3390/diseases12030044
Authors: Félix Úbeda Sonia Santander María José Luesma
Introduction: Hereditary fructose intolerance or hereditary fructosemia is an autosomal recessive metabolic disorder caused by a loss of function in the aldolase B gene. This disorder affects 1 in 20,000 people, constituting a rare disease with a favorable prognosis through adherence to a fructose-free diet. Despite dietary management, chronic pathology may manifest, underscoring the importance of early diagnosis to mitigate adverse effects. However, early detection of the disease poses significant challenges. Aim: Our aim was to compile pertinent information on the differential diagnosis of this pathology based on patient symptoms, facilitating the development of a diagnostic algorithm for early identification. Methodology: A systematic review adhering to PRISMA guidelines was conducted on empirical studies from PubMed, encompassing a total of 35 studies. Results: Individuals with fructose intolerance may acutely experience postprandial symptoms such as hypoglycemia, vomiting, and abdominal distension. Despite proper treatment, chronic complications such as fatty liver, Fanconi syndrome, growth deficiency, and irritable bowel syndrome may arise. The proposed diagnostic algorithm aims to minimize these adverse processes. Conclusions: Understanding the pathogenesis enables prompt diagnosis and prevention of chronicity. Establishing continuity of care from pediatric to adult medicine is crucial, and disseminating information to non-pediatric endocrinologists is imperative for managing this rare disease.
]]>Diseases doi: 10.3390/diseases12030043
Authors: Giuseppina Fanelli Veronica Lelli Sara Rinalducci Anna Maria Timperio
The immune response to infectious diseases is directly influenced by metabolic activities. COVID-19 is a disease that affects the entire body and can significantly impact cellular metabolism. Recent studies have focused their analysis on the potential connections between post-infection stages of SARS-CoV2 and different metabolic pathways. The spike S1 antigen was found to have in vitro IgG antibody memory for PBMCs when obtaining PBMC cultures 60–90 days post infection, and a significant increase in S-adenosyl homocysteine, sarcosine, and arginine was detected by mass spectrometric analysis. The involvement of these metabolites in physiological recovery from viral infections and immune activity is well documented, and they may provide a new and simple method to better comprehend the impact of SARS-CoV2 on leukocytes. Moreover, there was a significant change in the metabolism of the tryptophan and urea cycle pathways in leukocytes with IgG memory. With these data, together with results from the literature, it seems that leukocyte metabolism is reprogrammed after viral pathogenesis by activating certain amino acid pathways, which may be related to protective immunity against SARS-CoV2.
]]>Diseases doi: 10.3390/diseases12030042
Authors: Josip Lukenda Josip Andelo Borovac
The impact of the COVID-19 pandemic on cardiovascular healthcare in Croatia remains largely unexplored. This study aimed to compare the utilization and provision of cardiovascular services during the pre-pandemic (2017–2019) and pandemic (2020–2021) periods, leveraging nationwide data from the Croatian Health Insurance Fund, which covers 95% of all insurance claims in the country. Our findings reveal that while the use of coronary angiographies decreased during the pandemic, there was a notable increase in the utilization of advanced heart failure treatment modalities and percutaneous coronary interventions, particularly in the context of acute myocardial infarction. Additionally, transcatheter aortic valve implantations saw a significant rise during the pandemic period. Furthermore, laboratory diagnostic testing for troponin and natriuretic peptides experienced a marked increase, while the utilization of most other cardiovascular services remained stable or showed only minor declines compared to the pre-pandemic era. These observations suggest that the Croatian cardiovascular healthcare system displayed resilience during the COVID-19 pandemic, successfully maintaining and even expanding access to various diagnostic and interventional procedures despite facing widespread societal and logistical challenges.
]]>Diseases doi: 10.3390/diseases12030041
Authors: Massimo Franchini Daniele Focosi Mario Cruciani Michael J. Joyner Liise-anne Pirofski Jonathon W. Senefeld Shmuel Shoham David J. Sullivan Arturo Casadevall
Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56–0.97; p = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34–1.51; p = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids.
]]>Diseases doi: 10.3390/diseases12020040
Authors: Anna Angelousi Dimitrios C. Ziogas Vasiliki Siampanopoulou Chrysoula Mytareli Amalia Anastasopoulou George Lyrarakis Helen Gogas
Background: Checkpoint inhibitor (CPI)-associated diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE) that presents with variable clinical manifestations. Data about its pathogenesis have not yet been adequately studied. Methods: Applying the recently updated diagnostic criteria from the American Diabetes Association, we retrospectively reviewed the medical records of all CPI-treated patients referred to our endocrinological unit for managing their endocrine irAEs and analyzed the incidence of CPI-DM, its clinical characteristics, and its management. Results: Among the 326 CPI-treated patients with endocrine irAEs, 4 patients met the updated criteria for the diagnosis of CPI-DM, representing 1.22% of all endocrine irAEs in our cohort. These four patients presented with distinct clinical scenarios regarding the irAE onset, the underlying malignancy, the administered CPI regimen, and the type of circulating autoantibodies. Conclusion: The variable presentation of CPI-DM and the non-standard sensitivity of the presence of the type 1 DM traditional autoantibodies highlight the need for distinct guidelines and increased awareness of its diagnosis and management.
]]>Diseases doi: 10.3390/diseases12020039
Authors: Kenji Yamagata Satoshi Fukuzawa Atsuro Noguchi Shohei Takaoka Fumihiko Uchida Naomi Ishibashi-Kanno Hiroki Bukawa
Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.
]]>Diseases doi: 10.3390/diseases12020038
Authors: Alexandrina Nastasă Mohamad Hussam Sahloul Corneliu Iorgulescu Ștefan Bogdan Alina Scărlătescu Steliana Paja Adelina Pupaza Raluca Mitran Viviana Gondos Radu Gabriel Vătășescu
Background: Catheter ablation (CA) for atrial fibrillation (AF) is superior to antiarrhythmic drugs in maintaining sinus rhythm. Novel evidence suggests that increasing the time between the first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), is a predictor for AF recurrence post-ablation. Purpose: Our primary objective was to investigate the relationship between DAT and AF recurrence after a first ablation. Methods: Patients with AF who underwent CA in our center were enrolled consecutively, and a retrospective analysis was performed. DAT was treated as a continuous variable and reported as a median for the group with recurrence and the group without recurrence. DAT was also considered as a categorical variable and patients were stratified into three categories: DAT < 1 year, DAT < 2 years, and DAT < 4 years. Results: The cohort included 107 patients, with a mean age of 54.3 ± 11.7 years. Mean DAT was significantly longer in those with AF recurrence: 4.9(3.06) years versus 3.99(3.5) (p = 0.04). The Kaplan–Meier curve revealed a higher likelihood of AF-free status over time for patients with DAT < 2 years compared to those with DAT > 2 years (p = 0.04). Cox multivariate analysis indicated that left atrial volume index (LAVI), obstructive sleep apnoea (OSA), and DAT > 2 years were independently associated with AF recurrence after a single AF ablation procedure (p = 0.007, p = 0.02, and p = 0.03, respectively). Conclusion: A shorter duration between the first AF diagnosis and AF ablation is associated with an increased likelihood of procedural success after a single AF ablation procedure.
]]>Diseases doi: 10.3390/diseases12020037
Authors: Natalie Shi Qi Wong Chang Liu Molly Tzu-Yu Lin Isabelle Xin Yu Lee Louis Tong Yu-Chi Liu
Introduction: This is a case report of a patient with neuropathic corneal pain after coronavirus disease 2019 (COVID-19) infection. Methods: A previously healthy 27-year-old female presented with bilateral eye pain accompanied by increased light sensitivity 5 months after COVID-19 infection. She was diagnosed with neuropathic corneal pain based on clear corneas without fluorescein staining, alongside the presence of microneuromas, dendritic cells, and activated stromal keratocytes identified bilaterally on in vivo confocal microscopy. Results: The patient’s tear nerve growth factor, substance P, and calcitonin gene-related peptide levels were 5.9 pg/mL, 2978.7 pg/mL, and 1.1 ng/mL, respectively, for the right eye and 23.1 pg/mL, 4798.7 pg/mL, and 1.2 ng/mL, respectively, for the left eye, suggesting corneal neuroinflammatory status. After 6 weeks of topical 0.1% flurometholone treatment, decreased microneuroma size, less extensive dendritic cells, and reduced tear nerve growth factor and substance P levels were observed. The scores on the Ocular Pain Assessment Survey showed an improvement in burning sensation and light sensitivity, decreasing from 80% and 70% to 50% for both. Conclusions: Neuropathic corneal pain is a potential post-COVID-19 complication that warrants ophthalmologists’ and neurologists’ attention.
]]>Diseases doi: 10.3390/diseases12020036
Authors: Koju Kamoi Kyoko Ohno-Matsui
mRNA COVID-19 vaccines have been reported as protecting against COVID-19 and reducing its severity, and we have recognized post-vaccination symptoms recently. This research investigates the clinical trajectories of ocular disorders in a 51-year-old female who received a second dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. Exhibiting fever and blurred vision within 24 h post-vaccination, with progressive blurry vision over two months, she underwent in-depth ophthalmologic examinations, revealing intraocular cellular infiltration in anterior chamber, vitreous opacity, and frosted branch angiitis in both eyes. Comprehensive evaluations, including systemic workups as well as ocular and blood specimen analyses, excluded autoimmune and infectious etiologies, consolidating the diagnosis of vaccine-induced ocular inflammation. Despite adherence to prevailing therapeutic protocols, her condition showed no significant improvement over 18 months, pointing to a possible long post-COVID vaccination syndrome. Such persistent sequelae underscore the need for detailed studies to discern the interactions between vaccine-induced immune responses and the development of post-vaccination sequelae. Continual documentation of patients with long post-COVID vaccination syndrome is now essential to better understand the vaccine’s immunological effects, aiding in improving global vaccination strategies.
]]>Diseases doi: 10.3390/diseases12020035
Authors: Nelson Lu Hooman Vaseli Mobina Mahdavi Fatemah Taheri Dezaki Christina Luong Darwin Yeung Ken Gin Michael Tsang Parvathy Nair John Jue Marion Barnes Delaram Behnami Purang Abolmaesumi Teresa S. M. Tsang
Background: Automated rhythm detection on echocardiography through artificial intelligence (AI) has yet to be fully realized. We propose an AI model trained to identify atrial fibrillation (AF) using apical 4-chamber (AP4) cines without requiring electrocardiogram (ECG) data. Methods: Transthoracic echocardiography studies of consecutive patients ≥ 18 years old at our tertiary care centre were retrospectively reviewed for AF and sinus rhythm. The study was first interpreted by level III-trained echocardiography cardiologists as the gold standard for rhythm diagnosis based on ECG rhythm strip and imaging assessment, which was also verified with a 12-lead ECG around the time of the study. AP4 cines with three cardiac cycles were then extracted from these studies with the rhythm strip and Doppler information removed and introduced to the deep learning model ResNet(2+1)D with an 80:10:10 training–validation–test split ratio. Results: 634 patient studies (1205 cines) were included. After training, the AI model achieved high accuracy on validation for detection of both AF and sinus rhythm (mean F1-score = 0.92; AUROC = 0.95). Performance was consistent on the test dataset (mean F1-score = 0.94, AUROC = 0.98) when using the cardiologist’s assessment of the ECG rhythm strip as the gold standard, who had access to the full study and external ECG data, while the AI model did not. Conclusions: AF detection by AI on echocardiography without ECG appears accurate when compared to an echocardiography cardiologist’s assessment of the ECG rhythm strip as the gold standard. This has potential clinical implications in point-of-care ultrasound and stroke risk stratification.
]]>Diseases doi: 10.3390/diseases12020034
Authors: Vladimira Durmanova Miroslav Tedla Dusan Rada Helena Bandzuchova Daniel Kuba Magda Suchankova Agata Ocenasova Maria Bucova
HLA-G is the checkpoint molecule involved in the suppression of the immune response. Increased expression of HLA-G and its ILTs receptors have been correlated with tumor progression in various cancer types. In head and neck squamous cell carcinoma (HNSCC) tumors, the effect of HLA-G, ILT2 and ILT4 expression on cancer development has to be explained. The 34 HNSCC patients and 98 controls were genotyped for the HLA-G 14 bp ins/del polymorphism. In HNSCC lesions, HLA-G, ILT2 and ILT4 mRNA expression was analysed using real-time PCR. The association between HLA-G, ILT2 and ILT4 mRNA expression and clinical variables (age at onset, TNM staging system and p16 positivity) was also evaluated. No genetic association between the HLA-G 14 bp ins/del and HNSCC risk was detected (p > 0.05). However, in the non-metastatic HNSCC group, a significantly higher HLA-G mRNA expression was noted in tumors in the T4 stage compared to those in the T1 and T2 stages (p = 0.0289). ILT2 mRNA expression was significantly increased in non-metastatic vs. metastatic tumors (p = 0.0269). Furthermore, a significantly higher ILT4 mRNA expression was noted in tumors in the T1+T2 stage compared to those in the T3 stage (p = 0.0495). Our results suggest that the HLA-G molecule creates an immunological microenvironment involved in HNSCC development.
]]>Diseases doi: 10.3390/diseases12020033
Authors: Sonia Gentile Liam R. Sullivan Heather Brooks Gordana Simeunovic
Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (mAb), may be an effective treatment in this population. Real-world data on PAT effectiveness are limited. To evaluate response to PAT measured through 90-day all-cause morbidity and mortality, we performed a retrospective review of patients who contracted COVID-19 within a year from the last BCDT. From 64 included patients, the majority were Caucasians (95%), female (56%), vaccinated (67%), treated outpatients (64%), with multiple comorbidities. Examined BCDT were rituximab (55%), obinutuzumab (33%), ocrelizumab (11%) and ofatumumab (1%), used for underlying hematological malignancy (HEM) (40%), multiple sclerosis (34%), and rheumatoid arthritis (16%). Of seven deceased patients, three died from COVID-19. All three were elderly males with multiple comorbidities, treated inpatient for severe COVID-19. Four of 41 patients treated as outpatients were hospitalized for non-COVID-19-related reasons. All deceased and hospitalized patients had an underlying HEM. All but one were on rituximab. PAT may be an effective treatment for patients receiving BCDT, especially if given early for non-severe disease. Patients with underlying HEM may be at increased risk for severe disease compared with others receiving the same BCDT.
]]>Diseases doi: 10.3390/diseases12020032
Authors: Ebele C. Okoye Amal K. Mitra Terica Lomax Cedric Nunaley
About half of the world’s population is at risk of dengue infection. Epidemics of dengue fever have caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines and searching multiple databases, including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0–17 years old). Quality assessment was analyzed using the Cochrane Collaboration criteria, while data synthesis was conducted using thematic analysis and meta-analysis. Among the 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. The CYD-TDV (Dengvaxia®) and Tekade (TAK-003) vaccines showed strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines showed promising efficacy and immune response, particularly against severe manifestations.
]]>Diseases doi: 10.3390/diseases12020031
Authors: Saleh Ahmed Shabiha Sultana Shoumik Kundu Sayeda Sadia Alam Tareq Hossan Md Asiful Islam
Zika virus (ZIKV) and chikungunya virus (CHIKV) are arthropod-borne viruses with significant pathogenicity, posing a substantial health and economic burden on a global scale. Moreover, ZIKV-CHIKV coinfection imposes additional therapeutic challenges as there is no specific treatment for ZIKV or CHIKV infection. While a growing number of studies have documented the ZIKV-CHIKV coinfection, there is currently a lack of conclusive reports on this coinfection. Therefore, we performed a systematic review and meta-analysis to determine the true statistics of ZIKV-CHIKV coinfection in the global human population. Relevant studies were searched for in PubMed, Scopus, and Google Scholar without limitation in terms of language or publication date. A total of 33 studies containing 41,460 participants were included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42020176409. The pooled prevalence and confidence intervals of ZIKV-CHIKV coinfection were computed using a random-effects model. The study estimated a combined global prevalence rate of 1.0% [95% CI: 0.7–1.2] for the occurrence of ZIKV-CHIKV coinfection. The region of North America (Mexico, Haiti, and Nicaragua) and the country of Haiti demonstrated maximum prevalence rates of 2.8% [95% CI: 1.5–4.1] and 3.5% [95% CI: 0.2–6.8], respectively. Moreover, the prevalence of coinfection was found to be higher in the paediatric group (2.1% [95% CI: 0.0–4.2]) in comparison with the adult group (0.7% [95% CI: 0.2–1.1]). These findings suggest that the occurrence of ZIKV-CHIKV coinfection varies geographically and by age group. The results of this meta-analysis will guide future investigations seeking to understand the underlying reasons for these variations and the causes of coinfection and to develop targeted prevention and control strategies.
]]>Diseases doi: 10.3390/diseases12020030
Authors: Rumiko Shimizu Nobuto Nakanishi Manabu Ishihara Jun Oto Joji Kotani
Lean body mass is a significant component of survival from sepsis. Several equations can be used for calculating lean body mass based on age, sex, body weight, and height. We hypothesized that lean body mass is a better predictor of outcomes than the body mass index (BMI). This study used a multicenter cohort study database. The inclusion criteria were age ≥18 years and a diagnosis of sepsis or septic shock. BMI was classified into four categories: underweight (<18.5 kg/m2), normal (≥18.5–<25 kg/m2), overweight (≥25–<30 kg/m2), and obese (≥30 kg/m2). Four lean body mass equations were used and categorized on the basis of quartiles. The outcome was in-hospital mortality among different BMI and lean body mass groups. Among 85,558 patients, 3916 with sepsis were included in the analysis. Regarding BMI, in-hospital mortality was 36.9%, 29.8%, 26.7%, and 27.9% in patients who were underweight, normal weight, overweight, and obese, respectively (p < 0.01). High lean body mass did not show decreased mortality in all four equations. In critically ill patients with sepsis, BMI was a better predictor of in-hospital mortality than the lean body mass equation at intensive care unit (ICU) admission. To precisely predict in-hospital mortality, ICU-specific lean body mass equations are needed.
]]>Diseases doi: 10.3390/diseases12010029
Authors: Ingrid Siciliano Horbach Adriana de Souza Azevedo Waleska Dias Schwarcz Nathalia dos Santos Alves Brenda de Moura Dias Bruno Pimenta Setatino Luma da Cruz Moura Ariane Faria de Souza Caio Bidueira Denani Stephanie Almeida da Silva Thiago Goes Pimentel Victor de Oliveira Silva Ferreira Tamiris Azamor Ana Paula Dinis Ano Bom Maria da Penha Gomes Gouvea José Geraldo Mill Valéria Valim Jessica Polese Ana Carolina Campi-Azevedo Vanessa Peruhype-Magalhães Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Sheila Maria Barbosa de Lima Ivanildo Pedro de Sousa Junior
Massive vaccination positively impacted the SARS-CoV-2 pandemic, being a strategy to increase the titers of neutralizing antibodies (NAbs) in the population. Assessing NAb levels and understanding the kinetics of NAb responses is critical for evaluating immune protection. In this study, we optimized and validated a PRNT50 assay to assess 50% virus neutralization and evaluated its accuracy to measure NAbs to the original strain or variant of SARS-CoV-2. The optimal settings were selected, such as the cell (2 × 105 cells/well) and CMC (1.5%) concentrations and the viral input (~60 PFU/well) for PRNT-SARS-CoV-2 with cut-off point = 1.64 log5 based on the ROC curve (AUC = 0.999). The validated PRNT-SARS-CoV-2 assay presented high accuracy with an intraassay precision of 100% for testing samples with different NAb levels (low, medium, and high titers). The method displays high selectivity without cross-reactivity with dengue (DENV), measles (MV), zika (ZIKV), and yellow fever (YFV) viruses. In addition, the standardized PRNT-SARS-CoV-2 assay presented robustness when submitted to controlled variations. The validated PRNT assay was employed to test over 1000 specimens from subjects with positive or negative diagnoses for SARS-CoV-2 infection. Patients with severe COVID-19 exhibited higher levels of NAbs than those presenting mild symptoms for both the Wuhan strain and Omicron. In conclusion, this study provides a detailed description of an optimized and validated PRNT50 assay to monitor immune protection and to subsidize surveillance policies applied to epidemiologic studies of COVID-19.
]]>Diseases doi: 10.3390/diseases12010028
Authors: Diana Rodríguez-Vera Juan Rodrigo Salazar Marvin A. Soriano-Ursúa Jessica Guzmán-Pérez Arely Vergara-Castañeda Horacio Muñoz-Durán Gabriela L. Ramírez-Velez Alonso Vivar-Sierra Carlos Rogelio Naranjo-Navarro Patricia A. Meza-Meneses Marco A. Loza-Mejía Rodolfo Pinto-Almazán
Background and Objectives: The development of severe COVID-19 is related to the preexistence of comorbidities and an inadequate nutritional status. The latter is a critical factor for the development of infection and the progression of the disease. Notably, optimal nutrition impacts immune system function, as malnutrition is related to high cytokine levels in the late phase of the disease, correlating with a poor prognosis. In this sense, omega-3 fatty acids (O3FAs) have anti-inflammatory properties that may reduce morbidity and mortality from COVID-19 infection. O3FAs are linked to a better prognosis in COVID-19 patients. Materials and Methods: In this randomized, double-blind clinical trial, we evaluate the administration of O3FAs to unvaccinated Mexican patients for two weeks starting after the first two hours of hospitalization. Results: The findings support the notion that O3FAs (in a dose high enough to satisfy human physiological requirements in a short time, one capsule of 1.4 g O3FAs daily) exert a comprehensive multi-systemic modulatory influence, affecting inflammatory and metabolic pathways. Significant perturbations in biomarkers, including absolute neutrophil count, hematocrit, and platelet indices, underscore the compound’s anti-inflammatory effect. Concurrently, the intervention modulates pivotal metabolic and hepatic parameters, attenuating cardiovascular risk profiles and expediting patient convalescence. These multifarious effects are likely orchestrated through intricate biochemical mechanisms and are subject to individual variations predicated on metabolic factors. Conclusions: The results of this trial support the notion that O3FA supplementation has beneficial effects on COVID-19 patients with moderate presentation by regulating metabolism and limiting inflammation.
]]>Diseases doi: 10.3390/diseases12010027
Authors: Pavol Zubor Caroline Marie Henriksen Maren Elvenes Økstad Erika Cerskuviene Jozef Visnovsky Karol Kajo Andrey Valkov Kristen Olav Lind
A desmoid tumor (DT) is a rare benign neoplasm arising from muscle aponeurosis, associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When it occurs in pregnancy, the pregnancy and delivery is taken as an individual case for optimal management by physicians and midwifes, who need to be cautious in finding the optimal delivery mode for the patient, which depends on the tumor size, location, behavior, and past history. The authors report a case of 29-year-old pregnant woman who previously underwent systemic oncological treatment for a large abdominal wall desmoid tumor and became pregnant afterwards. The history of DT presented a follow-up and delivery challenge. Observational management was chosen with an elective cesarean section at week 38 + 4 of pregnancy with uncomplicated postpartum follow-up. The authors detail the clinical management and chosen therapeutic approach; chemotherapy can be a choice in the treatment options for patients with DTs, although the majority of DTs are treated surgically with subsequent mesh plastic. Moreover, the authors provide a systematic review of the literature focused on the treatment management of DTs in pregnant women during pregnancy and the postpartum period, as pregnancy-associated desmoid tumors are a specific condition, where the optimal management is not well established, despite some guidelines for non-pregnant patients.
]]>Diseases doi: 10.3390/diseases12010026
Authors: Giuseppe Di Martino Fabrizio Cedrone Michela D’Addezio Camillo Odio Pamela Di Giovanni Edoardo Trebbi Livia Tognaccini Ferdinando Romano Tommaso Staniscia
(1) Background: Rotavirus is one of the leading causes of severe diarrhea and dehydration in infants and young children worldwide. The economic and social burden of rotavirus-related hospitalizations, particularly among children, remains a pressing concern for healthcare systems across the globe. Healthcare infrastructure and access to medical care can vary significantly within the region. Differences in the availability of healthcare facilities and the quality of care may influence the management and outcomes of rotavirus cases. (2) Methods: This was a retrospective study performed in the Abruzzo region, Italy. The study considered all hospitalization due to rotavirus gastroenteritis that occurred in the Abruzzo region from the year 2015 to 2021. Data were extracted from the hospital discharge records. The trend in hospital admissions, hospitalization costs and length of stay were evaluated and analyzed. (3) Results: A total of 664 admissions were reported during the study period. The incident rate grew till year 2019 with an annual percentage change of +13.9% (95%CI 12.6–15.2, p < 0.001). During the pandemic years, the incident rate showed a significant decrease with an annual percentage change of 12.5% (95%CI 15.5–9.3, p = 0.004). The length of stay of admissions was significantly higher among patients aged less than 1 year. (4) Conclusions: Rotavirus admission represents a heavy burden even in a high-income country such as Italy. These findings have the potential to inform targeted public health interventions, including vaccination strategies, and improve the overall well-being of children.
]]>Diseases doi: 10.3390/diseases12010025
Authors: Carla Guidi Neftj Ragusa Ilaria Mussinatto Francesca Parola Diego Luotti Giulia Calosso Eleonora Rotondo Virginia Deut Fabio Timeus Adalberto Brach del Prever Massimo Berger
Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent; however, other viruses can be involved in this disease. We retrospectively reviewed the clinical features of infants aged less than 12 months hospitalized for acute bronchiolitis in our Pediatric Units of Chivasso, Cirié, and Ivrea in Piedmont, Northern Italy, over two consecutive bronchiolitis seasons (September 2021–March 2022 and September 2022–March 2023). Patient-, disease-, and treatment-related variables were analyzed. The probability of therapeutic success (discharge home) was 96% for all patients (93% for RSV vs. 98% for non-RSV patients, p > 0.05). Among 192 patients, 42 infants (22%) underwent high-flow oxygen support (HFNC), and only 8 (4%) needed to be transferred to our hub referral hospital. Factors associated with hub hospital transfer were the age under 1 month and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved the management of bronchiolitis in Spoke hospitals, reducing transfer to a hub hospital provided with Intensive Care Units.
]]>Diseases doi: 10.3390/diseases12010024
Authors: Jakub Bargiel Michał Gontarz Krzysztof Gąsiorowski Tomasz Marecik Paweł Wrona Jan Zapała Grażyna Wyszyńska-Pawelec
(1) Background: “Eagle Syndrome”, also known as “stylalgia” or a “stylohyoid chain anomaly”, typically manifests with ipsilateral orofacial pain, a foreign body sensation in the throat, and ear-related symptoms. Despite these common presentations, its potential association with carotid artery dissection is not widely acknowledged. (2) Methods: This article presents an extremely rare case of a patient diagnosed with an ischemic stroke in the left hemisphere, followed by the dissection of the left internal carotid artery, initially with an unidentified cause. Subsequent examinations revealed elongated left styloid processes directly compressing the dissected artery. (3) Results: After initial treatment involving pharmacological and mechanical thrombectomy, styloidectomy restored blood flow to the internal carotid artery. The patient remained symptom-free during a 12-month follow-up. (4) Conclusions: This case emphasizes the importance of considering anatomical variations within the stylohyoid chain when assessing young individuals with neurological symptoms. Furthermore, it underscores the potential benefits of early surgical intervention in reducing the morbidity and mortality associated with this condition.
]]>Diseases doi: 10.3390/diseases12010023
Authors: Ioannis Bellos Smaragdi Marinaki Evangelia Samoli Ioannis N. Boletis Vassiliki Benetou
This meta-analysis aims to assess current evidence regarding sociodemographic disparities among adults with kidney failure. Medline, Scopus, Web of Science, CENTRAL, and Google Scholar were systematically searched from inception to 20 February 2022. Overall, 165 cohort studies were included. Compared to White patients, dialysis survival was significantly better among Black (hazard ratio—HR: 0.68; 95% CI: 0.61–0.75), Asian (HR: 0.67; 95% CI: 0.61–0.72) and Hispanic patients (HR: 0.80; 95% CI: 0.73–0.88). Black individuals were associated with lower rates of successful arteriovenous fistula use, peritoneal dialysis and kidney transplantation, as well as with worse graft survival. Overall survival was significantly better in females after kidney transplantation compared to males (HR: 0.87; 95% CI: 0.84–0.90). Female sex was linked to higher rates of central venous catheter use and a lower probability of kidney transplantation. Indices of low SES were associated with higher mortality risk (HR: 1.22, 95% CI: 1.14–1.31), reduced rates of dialysis with an arteriovenous fistula, peritoneal dialysis and kidney transplantation, as well as higher graft failure risk. In conclusion, Black, Asian and Hispanic patients present better survival in dialysis, while Black, female and socially deprived patients demonstrate lower rates of successful arteriovenous fistula use and limited access to kidney transplantation. PROSPERO registration: CRD42022300839.
]]>Diseases doi: 10.3390/diseases12010022
Authors: Severo Vázquez-Prieto Antonio Vaamonde Esperanza Paniagua
In the present work, we examined the consumption of systemic antifungals (fluconazole, itraconazole, and terbinafine) in outpatients in the four provinces of Galicia, Spain, between 2019 and 2022. We also described the variability in the use of these types of drugs between these provinces. In addition, we detected any deviation in consumption at a seasonal level and analyzed possible changes during the study period. A descriptive, cross-sectional, and retrospective study of the use of antifungals, expressed in terms of a defined daily dose per 1000 inhabitants per day, was carried out. The results obtained revealed statistically significant differences between provinces and by the active principle consumed in the four Galician provinces (p < 0.001), which can be explained by multiple factors. This study also revealed that there was stable consumption during the study period, with no significant seasonal differences observed. This study represents a contribution to the knowledge about the consumption of antifungals for systemic use in Galicia and serves as a basis for subsequent studies. This will allow us to understand the consumption patterns of these types of drugs and, ultimately, will help to establish stewardship strategies and prevent the development of resistance.
]]>Diseases doi: 10.3390/diseases12010021
Authors: Adrian Vasile Bota Felix Bratosin Iulia Bogdan Susa Septimiu-Radu Adrian Cosmin Ilie Sonia-Roxana Burtic David Vladut Razvan Raluca Tudor Mirela Florica Indries Andrei Nicolae Csep Ariadna Petronela Fildan Camelia Melania Budea Iosif Marincu
This longitudinal study investigates the psychosocial effects of long-COVID Syndrome, a domain still not extensively researched. It specifically evaluates the quality of life, coping mechanisms, anxiety and depression levels in COVID-19 survivors, differentiating between those with and without long-COVID Syndrome. Conducted at the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania, the study utilized a cohort of patients diagnosed with mild to moderate COVID-19. The following standardized tools: WHOQOL-BREF for quality of life, COPE-60 for coping strategies, and the Hospital Anxiety and Depression Scale (HADS), were employed for the assessment. The sample consisted of 86 patients displaying persistent post-acute symptoms and 432 asymptomatic patients at the 6-month post-discharge mark. Patients with frequent post-acute symptoms reported significantly higher levels of fatigue (8.2 ± 1.4), cognitive difficulties (7.5 ± 1.6), and respiratory challenges (7.8 ± 1.3), along with a markedly lower overall quality of life (7.0 ± 1.5) compared to their asymptomatic counterparts. HADS scores revealed elevated depression (6.8 ± 1.9) and anxiety (7.1 ± 2.3) in the symptomatic group. Quality of life, as evaluated through the use of WHOQOL-BREF, showed lower scores in the symptomatic cohort across physical (58.8 ± 15.8), mental (56.3 ± 16.4), and social domains (50.2 ± 17.5). COPE-60 findings indicated a higher prevalence of disengagement (56.4%) and emotion-focused coping strategies (61.8%) in the symptomatic group, in contrast to 30.1% and 37.0%, respectively, in the asymptomatic group. The study highlights that long-COVID Syndrome significantly deteriorates the quality of life and is associated with increased depression and anxiety levels. The prevalent use of disengagement and emotion-focused coping strategies among patients with persistent symptoms suggests a need for enhanced psychosocial support tailored to this subgroup.
]]>Diseases doi: 10.3390/diseases12010020
Authors: Zhaona Yang Shouzhi Yu Ying Xu Yuxiu Zhao Lili Li Jingjie Sun Xin Wang Yancen Guo Yuntao Zhang
Influenza is a potentially fatal acute respiratory viral disease caused by the influenza virus. Influenza viruses vary in antigenicity and spread rapidly, resulting in seasonal epidemics. Vaccination is the most effective strategy for lowering the incidence and fatality rates of influenza-related disorders, and it is also an important method for reducing seasonal influenza infections. Mammalian Madin–Darby canine kidney (MDCK) cell lines are recommended for influenza virus growth, and such cell lines have been utilized in several commercial influenza vaccine productions. The limit dilution approach was used to screen ATCC-MDCK cell line subcellular strains that are especially sensitive to H1N1, H3N2, BV, and BY influenza viruses to increase virus production, and research on influenza virus culture media was performed to support influenza virus vaccine development. We also used RNA sequencing to identify differentially expressed genes and a GSEA analysis to determine the biological mechanisms underlying the various levels of susceptibility of cells to influenza viruses. MDCK cell subline 2B6 can be cultured to increase titer and the production of the H1N1, H3N2, BV, and BY influenza viruses. MDCK-2B6 has a significantly enriched and activated in ECM receptor interaction, JAK-STAT signaling, and cytokine receptor interaction signaling pathways, which may result in increased cellular susceptibility and cell proliferation activity to influenza viruses, promote viral adsorption and replication, and elevate viral production, ultimately. The study revealed that MDCK-2B6 can increase the influenza virus titer and yield in vaccine production by increasing cell sensitivity and enhancing proliferative activity.
]]>Diseases doi: 10.3390/diseases12010019
Authors: Bogdan Miutescu Deiana Vuletici Calin Burciu Felix Bende Iulia Ratiu Tudor Moga Eyad Gadour Shruta Reddy Vasile Sandru Gheorghe Balan Greta Dancu Felix-Mihai Maralescu Alina Popescu
This study aimed to compare microbial species and multidrug resistance patterns in acute cholangitis patients with and without a history of cholecystectomy, highlighting potential differences We hypothesized that post-cholecystectomy patients would exhibit distinct microbial spectra and resistance patterns. Conducted at a western Romanian hospital specializing in gastroenterology and hepatobiliary diseases from 2020 to 2023, this retrospective study included 488 acute cholangitis patients, divided into groups based on their cholecystectomy history. Bile and blood samples were analyzed for microbial identification and antibiotic susceptibility using VITEK®2. Positive biliary cultures were found in 66% of patients. The cholecystectomy group showed a higher prevalence of multidrug-resistant organisms, with 74.4% exhibiting resistance compared to 31.5% in the non-cholecystectomy group (p < 0.001). Notable microbial differences included higher occurrences of Escherichia coli (40.2%) and Enterococcus spp. (32.4%) in the cholecystectomy group. Resistance to Piperacillin/Tazobactam and Penems was significantly higher in this group, with odds ratios of 3.25 (p < 0.001) and 2.80 (p = 0.001), respectively, for the development of multidrug-resistant (MDR) bacterial species. The study confirmed our hypothesis, revealing distinct microbial profiles and a higher prevalence of multidrug resistance in acute cholangitis post-cholecystectomy patients. These findings underscore the need for tailored antibiotic strategies in managing acute cholangitis in this patient demographic.
]]>Diseases doi: 10.3390/diseases12010018
Authors: Filipa Malheiro Miguel Ângelo-Dias Teresa Lopes Sofia Azeredo-Lopes Catarina Martins Luis Miguel Borrego
Acute pancreatitis (AP) is an increasingly frequent disease in which inflammation plays a crucial role. Fifty patients hospitalized with AP were included and peripheral blood samples were analyzed for B and T cell subpopulations at the time of hospitalization and 48 h after diagnosis. The Bedside Index of Severity in Acute Pancreatitis (BISAP) and length of hospital stay were also recorded. A healthy control (HC) group of 15 outpatients was included. AP patients showed higher neutrophil/lymphocyte (N/L) ratios and higher percentages of B cells than the HC group. The total B cell percentages were higher in patients with moderate/severe AP than in patients with mild AP. The percentages of B cells as well as the percentages of the CD27−IgD− B cell subset decreased from admission to 48 h after admission. The patients with higher BISAP scores showed lower percentages of peripheral lymphocytes but higher percentages of CD27−IgD− B cells. Higher BISAP scores, N/L ratios, and peripheral blood B cell levels emerged as predictors of hospital stay length in AP patients. Our findings underscore the importance of early markers for disease severity. Additionally, the N/L ratio along with the BISAP score and circulating B cell levels form a robust predictive model for hospital stay duration of AP patients.
]]>Diseases doi: 10.3390/diseases12010017
Authors: Fabrizio Cedrone Vincenzo Montagna Livio Del Duca Laura Camplone Riccardo Mazzocca Federica Carfagnini Angela Ancona Omar Enzo Santangelo Valterio Fortunato Giuseppe Di Martino
Background: Severe respiratory infections, including pneumonia or bronchiolitis, caused by RSV can range from mild upper respiratory tract infections to those leading to hospitalization and serious complications such as respiratory failure in children. High-risk groups, such as premature infants and infants with underlying medical conditions, have a higher susceptibility to severe RSV disease. We conducted a retrospective study from years 2015 to 2022 in the Local Health Authority (LHA) of Pescara that counts about 320,000 inhabitants, with the aim to evaluate the burden of RSV infection, focusing on the incidence, hospitalization, and characteristics that may prolong hospital stays. Methods: All hospitalizations from 2015 to 2022 were extracted from the hospital discharge record. The monthly hospitalization rates were calculated and standardized by gender and age for the population resident in the Province of Pescara on 1 January 2015. Results: During the study period, 31,837 admissions were reported among patients aged less than 6 years. Of those, 520 hospitalizations were referred for bronchiolitis. Monthly admission rates highlighted the seasonality of bronchiolitis admissions, with higher rates in the months from December to March in all study years included. The winter seasons of years 2021 and 2022 reported a surge in bronchiolitis incidence, with a rate of 4.0/1000 (95% CI 2.964–5.146) in December 2021 and 4.0 (95% CI 2.891–5.020) in December 2022. Conclusions: Bronchiolitis represents an important cause of hospitalization among patients aged less than 6 years. The incidence was particularly increased during the winter seasons in years 2021 and 2022.
]]>Diseases doi: 10.3390/diseases12010016
Authors: Hagit Kopel Alina Bogdanov Jessamine P. Winer-Jones Christopher Adams Isabelle H. Winer Machaon Bonafede Van Hung Nguyen James A. Mansi
Influenza and COVID-19 contribute significantly to the infectious disease burden during the respiratory season, but their relative burden remains unknown. This study characterizes the frequency and severity of medically attended COVID-19 and influenza during the peak of the 2022–2023 influenza season in the pediatric, adult, and older adult populations and characterizes the prevalence of underlying conditions among patients hospitalized with COVID-19. This cross-sectional analysis included individuals in the Veradigm EHR Database linked to Komodo claims data with a medical encounter between 1 October 2022 and 31 March 2023 (study period). Patients with medical encounters were identified with a diagnosis of COVID-19 or influenza during the study period and stratified based on the highest level of care received with that diagnosis. Among 23,526,196 individuals, there were more COVID-19-related medical encounters than influenza-related encounters, overall and by outcome. Hospitalizations with COVID-19 were more common than hospitalizations with influenza overall (incidence ratio = 4.6) and in all age groups. Nearly all adults hospitalized with COVID-19 had at least one underlying medical condition, but 37.1% of 0–5-year-olds and 25.0% of 6–17-year-olds had no underlying medical conditions. COVID-19 was associated greater burden than influenza during the peak of the 2022–2023 influenza season.
]]>Diseases doi: 10.3390/diseases12010015
Authors: Luca Castiglione Marius Murariu Estera Boeriu Ileana Enatescu
This study hypothesized that botulinum toxin (Botox) therapy would sustainably reduce sweat production in axillary hyperhidrosis patients over one year and significantly improve various quality-of-life aspects, including psychological well-being, social interactions, and daily functioning. The objectives were to quantitatively measure changes in sweat production and qualitatively assess the evolving impact on patients’ quality of life over one year. Conducted prospectively at the Pius Brinzeu Clinical Emergency Hospital in Timisoara, Romania, this study complied with ethical standards and included adults with primary axillary hyperhidrosis unresponsive to conventional treatments. Participants underwent Botox injections and were evaluated at baseline, six months, and one year, using the Hyperhidrosis Disease Severity Scale (HDSS), WHOQOL-BREF, and the Dermatology Life Quality Index (DLQI), among other tools. Involving 81 patients, the study showed significant improvements in sweat production and quality-of-life metrics. Sweat production decreased from 0.81 g to 0.23 g per 15 min over one year (p < 0.001). HDSS scores reduced from 3.4 to 1.5, indicating a decrease in symptom severity (p < 0.001). The DLQI total score, assessing life quality impact, notably dropped from 19.9 to 6.9 (p < 0.001). Quality-of-life domains also showed significant improvements, especially in the social (from 65.3 to 73.4, p < 0.001) and environmental aspects (from 68.0 to 72.1, p < 0.001). Higher HDSS and sweat production were significantly associated with a lower quality of life on the DLQI (B coefficients of −4.1 and −2.5, respectively). Botulinum toxin therapy proved effective in reducing sweat production and improving the quality of life in axillary hyperhidrosis patients over a one-year period. These improvements were statistically significant in both physical and psychosocial domains. The study highlights the potential long-term benefits of Botox therapy for hyperhidrosis.
]]>Diseases doi: 10.3390/diseases12010014
Authors: Pajaree Krisanapan Kanokporn Sanpawithayakul Pattharawin Pattharanitima Charat Thongprayoon Jing Miao Michael A. Mao Supawadee Suppadungsuk Supawit Tangpanithandee Iasmina M. Craici Wisit Cheungpasitporn
Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies—of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of −1.2%; 95% CI −2.0, −0.4) and pro-BNP (SMD −335.9 pmol/L; 95% CI −438.9, −232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD −1.1 mg/dL; 95% CI −1.8, −0.3) and increased weight loss (SMD −2.2 kg; 95% CI −2.9, −1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.
]]>Diseases doi: 10.3390/diseases12010013
Authors: Shayan Fallah Nastaran Asri Abdolrahim Nikzamir Shokoufeh Ahmadipour Amir Sadeghi Kamran Rostami Mohammad Rostami-Nejad
Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFβ (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.
]]>Diseases doi: 10.3390/diseases12010012
Authors: Elena Aurora Popoca-Hernández Rita Elizabeth Martínez-Martínez Roberto Fidencio González-Amaro Perla del Carmen Niño-Moreno José Luis Ayala-Herrera Alberto Vinicio Jerezano-Domínguez Leon Francisco Espinosa-Cristóbal María de Lourdes Márquez-Corona Irene Aurora Espinosa-de Santillana Carlo Eduardo Medina-Solís
The aim of this study was to evaluate the impact of non-surgical periodontal treatment (NS-PT) on periodontal parameters and inflammatory biomarkers in the concentration and level of calprotectin (CLP) in women with periodontitis and rheumatoid arthritis (RA). In this quasi-experimental study, we evaluated 30 women (mean age: 52.0 ± 5.8 years) with periodontitis and RA who had been diagnosed and treated for RA for more than 3 years and whose activity markers remained at similar values without significant reduction over three consecutive months. Patients underwent NS-PT, which included plaque control, scaling, and root planing. Serum and saliva samples, periodontal indices, RA activity markers, Disease Activity Score-28 (DAS28), the erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) and CLP contents were measured at the beginning of the study and 6 and 12 weeks after NS-PT. Parametric and nonparametric tests were used in the analysis. The mean age was 52.0 ± 5.8 years. Compared to the baseline results, all periodontal indices were significantly reduced 6 and 12 weeks after NS-PT (p < 0.001). DAS28 was also significantly reduced after 12 weeks (p < 0.0001). Similarly, the serum CLP concentration decreased 6 and 12 weeks after NS-PT (p < 0.0001). Of the patients, 100% presented lower levels of CRP and ESR (p < 0.0001). Overall, NS-PT reduced inflammation and disease activity, highlighting the importance of oral health in the control and treatment of systemic diseases such as RA and confirming that NS-PT effectively reduces periodontitis activity and plays a key role in modulating RA activity. Therefore, NS-PT should be considered as an adjunct treatment for RA.
]]>Diseases doi: 10.3390/diseases12010011
Authors: Iulia Toma Anca Dinu Ahmed Abu-Awwad Mihai-Alexandru Sandesc Simona-Alina Abu-Awwad Razvan Nitu Mihai Popean
(1) Background: The Patterned Sensory Enhancement (PSE) technique refers to a music-based rehabilitation therapy strategy used in neurological pathologies. (2) Methods: This study aims at developing a music-drill protocol for recovery in elderly patients with neuromuscular degenerative pathologies. Each music drill is based on a number of specific music-composition parameters. The conclusions represent suggestions for further enhancing the PSE technique through collaborations between the rehabilitation team and the musicians involved due to the importance of the music stimuli used as a therapy. (3) Results: The music-composition parameters used in this study relate to the existence of music homogeneity factors such as the key signature and rhythm; the importance of the major scale and the tonal system in general; the obvious music suggestions of movement, repetition or absence of movement; the importance of rhythm; the introduction of musical instruments in order to harmonize the music material as much as possible; the connection between PSE music along with patients’ musical taste and the musical recording as a therapy during patient outcare; (4) Conclusions: The therapy efficiency was observed by measurements taken before and after the therapeutic intervention by means of a Takei dynamometer. The present study asserts that for a patient undergoing the PSE technique, the researcher should compose personalized music material adapted to each patient’s peculiarities.
]]>Diseases doi: 10.3390/diseases12010010
Authors: Carmen-Ioana Marta Marius Craina Razvan Nitu Anca Laura Maghiari Simona-Alina Abu-Awwad Lioara Boscu Mircea Diaconu Catalin Dumitru George Dahma Ionela-Iasmina Yasar Katalin Babes
Background: The cardiac biomarker NT-proBNP is released by the ventricles in response to increased cardiac wall tension, showing cardiac activity in heart failure. The primary objective of this comparative study was to analyze the variations of NT-proBNP levels among pregnant patients and to determine the potential influence of SARS-CoV-2 infection on these values. Secondly, the study focused on NT-proBNP levels and their influence on the type of birth. Methods: Blood samples were taken from 160 pregnant mothers in order to determine, through the solid-phase enzyme-linked immunosorbent assay (ELISA) method, the NT-proBNP concentrations from the plasma. The cohort was separated into two distinct groups based on SARS-CoV-2 diagnostic results: negative to the infection, and positive to the infection. Results: The SARS-CoV-2-positive group of patients presented with higher levels of NT-proBNP and had higher rates of cesarean sections. (4) Conclusions: Our research highlights the crucial relationship between elevated NT-proBNP values and the mode of giving birth, natural delivery or cesarean section, and also the influence of SARS-CoV-2 viral infection and this biomarker.
]]>Diseases doi: 10.3390/diseases12010009
Authors: Cesare Danesino Monica Gualtierotti Matteo Origi Angelina Cistaro Michela Malacarne Matteo Massidda Katia Bencardino Domenico Coviello Giovanni Albani Irene Giovanna Schiera Alexandra Liava Andrea Guala
Background: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs. Methods: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC). A high pain threshold was also observed. Conventional and molecular cytogenetic defined the size of the deletion, and exome analysis on the trio completed the molecular work. Results: Cytogenetic analysis showed a de novo chromosomal alteration: 46,XY,ishdel(5)(p14.3)(D5S28-) and arr[GRCh37] 5p15.33p14.3(1498180_19955760)x1. A quantitative sensory test demonstrated a high heat threshold. A 18f-fluorodeoxyglucose PET/TC scan of the brain failed to detect reduction of metabolism in the somatosensory area or insular cortex. Exome analysis in the trio (patient and parents) failed to identify variants to be interpreted as a likely risk factor for EAC. Conclusion: We conclude that the presence of well-known risk factors (maleness, obesity, gastroesophageal reflux, and Barrett’s metaplasia) in a patient with very limited capability of expressing discomfort or referring clinical symptoms have been the main risk factors for developing EAC. At present, based on the available data, there is no evidence of any increased risk of developing cancer in CdC patients.
]]>Diseases doi: 10.3390/diseases12010008
Authors: Jakub Batko Jakub Rusinek Artur Słomka Radosław Litwinowicz Marian Burysz Magdalena Bartuś Dhanunjaya R. Lakkireddy Randall J. Lee Joanna Natorska Michał Ząbczyk Bogusław Kapelak Krzysztof Bartuś
Left atrial appendage occlusion affects systemic coagulation parameters, leading to additional patient-related benefits. The aim of this study was to investigate the differences in coagulation factor changes 6 months after epicardial left atrial appendage occlusion in patients with different LAA morphometries. This is the first study to analyze these relationships in detail. A prospective study of 22 consecutive patients was performed. Plasminogen, fibrinogen, tPA concentration, PAI-1, TAFI and computed tomography angiograms were performed. Patients were divided into subgroups based on left atrial appendage body and orifice diameter enlargement. The results of blood tests at baseline and six-month follow-up were compared. In a population with normal LAA body size and normal orifice diameter size, a significant decrease in analyzed clotting factors was observed between baseline and follow-up for all parameters except plasminogen. A significant decrease between baseline and follow-up was observed with enlarged LAA body size in all parameters except TAFI, in which it was insignificant and plasminogen, in which a significant increase was observed. Occlusion of the left atrial appendage is beneficial for systemic coagulation. Patients with a small LAA may benefit more from LAA closure in terms of stabilizing their coagulation factors associated with potential thromboembolic events in the future.
]]>Diseases doi: 10.3390/diseases12010007
Authors: Bidisha Roy Enyonam Amemasor Suhail Hussain Kimberly Castro
Published reports from the CDC’s Autism and Development Disabilities Monitoring Networks have shown that an average of 1 in every 44 (2.3%) 8-year-old children were estimated to have ASD in 2018. Many of the ASDs exhibiting varying degrees of autism-like phenotypes have chromosomal anomalies in the Chr15q11–q13 region. Numerous potential candidate genes linked with ASD reside in this chromosomal segment. However, several clinical, in vivo, and in vitro studies selected one gene more frequently than others randomly and unbiasedly. This gene codes for UBE3A or Ubiquitin protein ligase E3A [also known as E6AP ubiquitin-protein ligase (E6AP)], an enzyme involved in the cellular degradation of proteins. This gene has been listed as one of the several genes with a high potential of causing ASD in the Autism Database. The gain of function mutations, triplication, or duplication in the UBE3A gene is also associated with ASDs like Angelman Syndrome (AS) and Dup15q Syndrome. The genetic imprinting of UBE3A in the brain and a preference for neuronal maternal-specific expression are the key features of various ASDs. Since the UBE3A gene is involved in two main important diseases associated with autism-like symptoms, there has been widespread research going on in understanding the link between this gene and autism. Additionally, since no universal methodology or mechanism exists for identifying UBE3A-mediated ASD, it continues to be challenging for neurobiologists, neuroscientists, and clinicians to design therapies or diagnostic tools. In this review, we focus on the structure and functional aspects of the UBE3A protein, discuss the primary relevance of the 15q11–q13 region in the cause of ASDs, and highlight the link between UBE3A and ASD. We try to broaden the knowledge of our readers by elaborating on the possible mechanisms underlying UBE3A-mediated ASDs, emphasizing the usage of UBE3A as a prospective biomarker in the preclinical diagnosis of ASDs and discuss the positive outcomes, advanced developments, and the hurdles in the field of therapeutic strategies against UBE3A-mediated ASDs. This review is novel as it lays a very detailed and comprehensive platform for one of the most important genes associated with diseases showing autistic-like symptoms. Additionally, this review also attempts to lay optimistic feedback on the possible steps for the diagnosis, prevention, and therapy of these UBE3A-mediated ASDs in the upcoming years.
]]>Diseases doi: 10.3390/diseases12010006
Authors: Patrycja Sosnowska-Sienkiewicz Przemysław Mańkowski Honorata Stadnik Agata Dłubak Anna Czekała Marek Karczewski
Introduction: Liposarcomas are the most common of all sarcomas. A well-differentiated liposarcoma can transform into a dedifferentiated liposarcoma with myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of MDM2 gene is then characteristic. Treatment usually involves surgical resection to radically remove the tumor. Other treatments such as chemotherapy and radiotherapy may also be used. Case report: A 60-year-old patient was admitted to the hospital for surgical treatment of a left renal mass. The true location of the tumor was discovered only intraoperatively. The lesion was completely removed laparoscopically with preservation of the capsule. Genomic amplification of MDM2 gene was confirmed. One and a half years after surgery, despite the removal of the tumor without the surrounding margin of healthy tissue, the patient remains without recurrence. Conclusion: Dedifferentiated liposarcoma with osteosarcomatous differentiation is a sporadic case and may occur in various locations of the retroperitoneal space, also mimicking a renal tumor. The laparoscopic technique is a safe surgical treatment for tumors of unclear origin. Removal of dedifferentiated liposarcoma with osteosarcomatous differentiation tumor with preservation of the lesion capsule without maintaining a margin of healthy tissue also allows for long-term cure. Precise immunohistochemical and molecular studies may have an impact on the effectiveness of further treatment and the prognosis of the patient. A patient after surgical treatment of liposarcoma requires constant outpatient follow-up for the reason of the high risk of local and distant recurrence.
]]>Diseases doi: 10.3390/diseases12010005
Authors: Eleonora Ianuà Mario Caldarelli Giuseppe De Matteis Rossella Cianci Giovanni Gambassi
Hemophilia A is a hemorrhagic disorder caused by insufficient or inadequate coagulation factor VIII activity. Two different forms are described: congenital, hereditary X-linked, and acquired. Acquired hemophilia A (AHA) is a rare condition and it is defined by the production of autoantibodies neutralizing factor VIII, known as inhibitors. We report the case of a 72-year-old man with a clinical diagnosis of AHA after SARS-CoV-2 infection, which has been described in association with several hematological complications. SARS-CoV-2 infection could represent the immunological trigger for the development of autoantibodies. In our patient, SARS-CoV-2 infection preceded the hemorrhagic complications by 15 days. This lag time is in line with the other cases reported and compatible with the development of an intense immune response with autoantibody production. It is possible that since our patient was affected by type 1 diabetes mellitus, he was more prone to an immune system pathological response against self-antigens. A prompt, appropriate therapeutic intervention with activated recombinant factor VII administration and cyclophosphamide has led to rapid remission of clinical and laboratory findings.
]]>Diseases doi: 10.3390/diseases12010004
Authors: Takuma Higurashi Shigeki Tamura Noboru Misawa Nobuyuki Horita
The impact of the COVID-19 pandemic was very broad and substantial, affecting a variety of fields worldwide. In Japan, the infection began spreading in March 2020. At that time, the government alerted people to cancel overseas travel, and encouraged wearing of masks, handwashing, sanitizing and keeping social distance. We sought to determine how COVID-19 infections affected other infectious diseases by investigating the trends in seven gastrointestinal infections that are listed among the 77 important infectious diseases designated by the National Institute of Infectious Diseases. We compared seven gastrointestinal infectious diseases, namely cholera, bacterial dysentery, enterohemorrhagic Escherichia coli, typhoid fever, paratyphoid fever, amoebic dysentery, and giardiasis, in terms of numbers of new cases before the COVID-19 pandemic (2012–2019) and during the pandemic (2020–2022). During the COVID-19 pandemic period (2020–2022), the incidence of the seven infections decreased significantly (p < 0.05) compared with before the pandemic (2012–2019). The sharp and significant decline in incidence of these seven infections in Japan during the COVID-19 pandemic period (2020–2022) appears to be due to restrictions on overseas travel and strict anti-infection measures, such as self-quarantine and encouragement of handwashing and sanitizing. The number of new cases of gastrointestinal infections in Japan is expected to increase in 2024 as these measures lapse. It is important for physicians to continue to monitor trends in gastrointestinal infections and educate people about proper infection prevention.
]]>Diseases doi: 10.3390/diseases12010003
Authors: Madalina-Ianca Suba Simona-Alina Abu-Awwad Ovidiu Rosca Mirela-Mădălina Turaiche Bogdan Hogea Ahmed Abu-Awwad Razvan Nitu Voichita Elena Lazureanu
Background: The battle against HIV has led to the development of antiretroviral therapy (ART), including BIKTARVY®, which combines three potent agents. However, concerns about gastrointestinal side effects during the early phases of treatment have emerged, potentially impacting patient adherence and outcomes. Materials and Methods: This retrospective cohort study, conducted over four years in Romania, examined 222 patients initiated on BIKTARVY® therapy. Data were collected from electronic medical records, and stringent inclusion and exclusion criteria were applied to ensure data accuracy and relevance. Statistical analysis was performed to assess age-related patterns in gastrointestinal symptoms and their relation with significant weight loss. Results: This study revealed significant differences in the prevalence of gastrointestinal symptoms between age groups, with older patients experiencing more symptoms. Notably, diarrhea did not exhibit a statistically significant age-related difference. Furthermore, weight loss exceeding 5 kg was more common in older patients. Of the patients who continued BIKTARVY® therapy, 84.9% showed an increase in CD4 cell counts, and most expressed satisfaction with treatment. Conclusion: Understanding age-related patterns and gastrointestinal side effects of BIKTARVY® is crucial for optimizing HIV patient care. Future research should aim to corroborate and expand upon these findings, potentially leading to improved therapeutic approaches in the ongoing fight against HIV.
]]>Diseases doi: 10.3390/diseases12010002
Authors: Hisham F. Bahmad Lauren Ramesar Cecilia Nosti Gameli Anthonio Carole Brathwaite Cristina Vincentelli Amilcar A. Castellano-Sánchez Robert Poppiti
The Journal retracts the article, Histopathologic Findings Associated with Miller–Dieker Syndrome: An Autopsy Report [...]
]]>Diseases doi: 10.3390/diseases12010001
Authors: Lamia Madaci Charlyne Gard Sébastien Nin Alexandre Sarrabay Céline Baier Geoffroy Venton Pascal Rihet Denis Puthier Béatrice Loriod Régis Costello
Introduction: The application of single-cell RNA sequencing has greatly improved our understanding of various cellular and molecular mechanisms involved in physiological and pathophysiological processes. However, obtaining living cells for this technique can be difficult under certain conditions. To solve this problem, the methanol fixation method appeared as a promising alternative for routine clinical use. Materials and Methods: In this study, we selected two AML samples that had been fixed in methanol for 12–18 months. Once the cells were rehydrated, these samples were subjected to single-cell RNA sequencing. We then compared the results obtained from these samples with those obtained from the same samples cryopreserved in DMSO. Results: We used a previously validated methanol fixation protocol to perform scRNA-seq on DMSO cryopreserved cells and cells fixed in methanol for more than one year. Preliminary results show that methanol fixation induces some genetic and transcriptional modification compared with DMSO cryopreservation but remains a valuable method for single-cell analysis of primary human leukemia cells. Conclusions: The initial findings from this study highlight certain resemblances in methanol fixation over a 12-month period and cryopreservation with DMSO, along with associated transcriptional level modifications. However, we observed genetic degradation in the fixation condition when extending beyond one year. Despite certain study limitations, it is evident that short-term methanol fixation can be effectively used for leukemia blast samples. Its ease of implementation holds the potential to simplify the integration of this technique into routine clinical practice.
]]>Diseases doi: 10.3390/diseases11040184
Authors: Qamraa H. Alqahtani Samiyah Alshehri Ahlam M. Alhusaini Wedad S. Sarawi Sana S. Alqarni Raessa Mohamed Meha N. Kumar Juman Al-Saab Iman H. Hasan
Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.
]]>Diseases doi: 10.3390/diseases11040183
Authors: Mohamed Abuelazm Shafaqat Ali Majd M. AlBarakat Abdelrahman Mahmoud Mohammad Tanashat Husam Abu Suilik Basel Abdelazeem James Robert Brašić
Istaroxime, an intravenous inotropic agent with a dual mechanism—increasing both cardiomyocyte contractility and relaxation—is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model—according to heterogeneity—to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m2) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: −0.39, 95% CI: −0.58, −0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: −3.05, 95% CI: −5.27, −0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.
]]>Diseases doi: 10.3390/diseases11040182
Authors: Hassan Zmerly Chiara Milanese Marwan El Ghoch Leila Itani Hana Tannir Dima Kreidieh Volkan Yumuk Massimo Pellegrini
Physical activity (PA) plays a vital role in knee osteoarthritis (KOA) management. However, engaging individuals with KOA in regular exercise is challenging, especially when they are affected by obesity. The aim of the current review is to elucidate how to increase adherence to exercise in this population. When implementing a PA program with patients with KOA and obesity, a specific multi-step approach can be adopted. In phase I (the baseline assessment), the patients’ eligibility for exercise is ascertained and a physical fitness assessment, sarcopenic obesity screening and quantification of the pain experienced are undertaken. Phase II adopts a patient-centered approach in implementing a PA program that combines an active lifestyle (>6000 steps/day) with land- or water-based exercise programs performed over eight to twelve weeks, with a frequency of three to five sessions per week, each lasting 60 min. In phase III, several strategies can be used to increase the patients’ adherence to higher levels of PA, including the following: (i) personalizing PA goal-setting and real-time monitoring; (ii) enhancing physical fitness and the management of sarcopenic obesity; (iii) building a sustainable environment and a supportive social network for an active lifestyle; and (iv) reducing pain, which can ameliorate the clinical severity of KOA and help with weight management in this population.
]]>Diseases doi: 10.3390/diseases11040181
Authors: Vlad Braicu Lazar Fulger Aditya Nelluri Ram Kiran Maganti Uday Shree Akkala Shetty Gabriel Verdes Dan Brebu Catalin Dumitru Ana-Olivia Toma Ovidiu Rosca Ciprian Duta
The global pandemic period from 2020 to 2022 caused important alterations in oncology care. This study aimed to describe the trends and variations in patient characteristics, comorbidities, and treatment approaches during this time in Romania. We conducted a retrospective database search to identify patients with rectal cancer who underwent surgical intervention between 2020 and 2022 and the year 2019, which served as a pre-pandemic period control. This study included 164 patients, with a yearly increase of approximately 10% in surgical interventions noted from 2020 (1709 interventions) to 2022 (2118 interventions), but an overall 34.4% decrease compared with the pre-pandemic period. Notable shifts were observed in the type of surgeries performed, with laparoscopic procedures doubling from 2020 (25%) to 2022 (47.5%), confirming the decrease in emergency presentations during the last year of the COVID-19 pandemic and a recovery to normality with planned, elective interventions. Elective interventions increased significantly in 2022 (79.7%) compared with the previous years (p = 0.043), with a concurrent rise in neoadjuvant therapy uptake in 2022 (35.6%). However, significant alterations in the TNM staging, from 12.5% stage IV cases in 2020 to 25.4% in 2022 (p = 0.039), indicated an increased diagnosis of advanced stages of rectal cancer as the years progressed. There was a significant difference in albumin levels over the years (p = 0.019) and in the American Society of Anesthesiology (ASA) scores (from 6.2% ASA stage IV in 2020 to 16.9% in 2022), denoting an increase in case complexity (p = 0.043). This study reveals a trend of increasing surgical interventions and the prevalence of more advanced stages of rectal cancer during the pandemic years. Despite the subtle fluctuations in various patient characteristics and treatment approaches, notable shifts were documented in the severity at diagnosis and surgery types, pointing toward more advanced disease presentations and changes in surgical strategies over the period studied. Nevertheless, the trends in ICU admission rates and mortality did not alter significantly during the pandemic period.
]]>Diseases doi: 10.3390/diseases11040180
Authors: Hugo Martinez-Rojano Herón Huerta Reyna Sámano Gabriela Chico-Barba Jennifer Mier-Cabrera Estibeyesbo Said Plascencia-Nieto
Objective: This review aims to describe and compare the risk factors, clinical course, diagnosis, and parasitologic features of external ophthalmomyiasis. We also discuss the different preventive measures and the effect of global warming in a large case series reported from January 2000 to December 2022. Methods: We perform a literature review of reported cases of external ophthalmomyiasis to determine the clinical characteristics, therapeutic management, and information on the organisms that most commonly cause external ophthalmomyiasis. Results: A total of 312 cases of external ophthalmomyiasis were recorded. The most common causative organism was Oestrus ovis (Linnaeus) (Diptera: Oestridae), accounting for 72.1% of cases, followed by Dermatobia hominis (Linnaeus Jr. in Pallas, 1781) (Diptera: Oestridae) at 5.4%, Lucilia sericata (Meigen) (Diptera: Calliphoridae) at 0.96%, and Chrysomyia bezziana (Villeneuve) (Diptera: Calliphoridae) at 0.96%. Before experiencing symptoms, 43.6% of cases reported having direct contact with flies or being hit in the eye, 33% reported no associated risk factors, 9.3% reported living with sheep and goats, and 7.7% reported a history of foreign objects entering the eye. The most common symptoms for those affected by O. ovis were sudden onset, including a foreign body sensation and movement, redness, tearing, itching, swelling, irritation, photophobia, burning, and ocular secretion. In cases caused by D. hominis, symptoms included eyelid edema, pain, redness, itching, movement within the lesion, ocular irritation, and discharge. Regarding occupational or recreational activity, agriculture, and livestock had the highest incidence, followed by trades and technical activities, being a student, and having traveled to an endemic region for work or recreation. Conclusion: Patients with red eyes may suffer from external ophthalmomyiasis, which requires a thorough examination to diagnose and treat it early. Moreover, as the temperature increases due to climate change, it is essential to consider how this will affect the spread of different pathogens.
]]>Diseases doi: 10.3390/diseases11040179
Authors: Elizabeth A. K. Jones Brenda Jenkins Clifton Addison
Alzheimer’s disease is the sixth most common cause of death in the United States (U.S.), with one in three adults 65 years of age and older dying of the disease each year. Deaths from Alzheimer’s have more than doubled between 2000 and 2019, killing more adults than both breast cancer and prostate cancer. In 2021, Alzheimer’s disease resulted in 36 deaths per 100,000 in the U.S. In Mississippi, deaths from Alzheimer’s have almost doubled between 2011 and 2021, resulting in 52.9 deaths per 100,000. Women have a higher mortality rate from Alzheimer’s than men. Alzheimer’s is a progressive disease that develops through seven stages. There are effective strategies to prevent the onset of Alzheimer’s. Methods: This paper reviews the risk factors, mortality trends, etiology, and prognosis of Alzheimer’s in Mississippi with a focus on prevention. Results: The southern diet with foods high in sugar and sodium, along with sedentary and poor lifestyle choices, increases mortality risk from Alzheimer’s disease for women in Mississippi, specifically due to women over 65 having higher rates of obesity and hypertension. Conclusion: Understanding the epidemiology and risk factors of Alzheimer’s in Mississippi will help inform communities, policies, and programs to prevent disease occurrence.
]]>Diseases doi: 10.3390/diseases11040178
Authors: Takahiro Kurihara Eisuke Amiya Masaru Hatano Junichi Ishida Shun Minatsuki Shunsuke Inoue Seitaro Nomura Hiroyuki Morita Issei Komuro
The co-occurrence of dilated cardiomyopathy (DCM) and aortic dissection has been rarely reported. Here, we present the case of a patient with co-occurrence of DCM and aortic dissection, wherein multivessel coronary artery dissection eventually occurred, thereby leading to advanced heart failure. She suffered from co-occurrence of DCM and aortic dissection 6 years ago. After the heart failure had briefly stabilized, the myocardial infarction due to coronary artery dissection led to worsening mitral regurgitation and decreased right ventricular function, thereby worsening the status of her heart failure. In addition to cardiovascular abnormalities, the patient was also complicated by short stature (145 cm), mild scoliosis, nonfunctioning pituitary adenoma of 1 cm in size, and retinitis pigmentosa. Coronary artery dissection is a possible complication in patients with co-occurrence of DCM and aortopathy, which could dramatically affect the clinical course of advanced heart failure.
]]>Diseases doi: 10.3390/diseases11040177
Authors: Nusrat Chowdhury Anup Kundu
The COVID-19 pandemic has had a profound impact on societies, public health, healthcare systems, and the world economy. With over 771 million people infected worldwide and a staggering death toll exceeding 6,960,783 as of 4 October 2023 (according to the World Health Organization), the urgency for a solution was paramount. Since the outbreak, the demand for immediate treatment for COVID-19 viral infection, as well as for effective vaccination against this virus, was soaring, which led scientists, pharmaceutical/biotech companies, government health agencies, etc., to think about a treatment strategy that could control and minimize this outbreak as soon as possible. Vaccination emerged as the most effective strategy to combat this infectious disease. For vaccination strategies, any conventional vaccine approach using attenuated live or inactivated/engineered virus, as well as other approaches, typically requires years of research and assessment. However, the urgency of the situation promoted a faster and more effective approach to vaccine development against COVID-19. The role of nanotechnology in designing, manufacturing, boosting, and delivering vaccines to the host to counter this virus was unquestionably valued and assessed. Several nanoformulations are discussed here in terms of their composition, physical properties, credibility, and applications in past vaccine development (as well as the possibility of using those used in previous applications for the generation of the COVID-19 vaccine). Controlling and eliminating the spread of the virus and preventing future recurrence requires a safe, tolerable, and effective vaccine strategy. In this review, we discuss the potential of nanoformulations as the basis for an effective vaccine strategy against COVID-19.
]]>Diseases doi: 10.3390/diseases11040176
Authors: Haoqi Zhou Jingyuan Wang Naseem Asghar Baosheng Liang Qianqian Song Xiaohua Zhou
(1) Background: The evidence indicates that comorbidities are associated with an increase in the risk of death from coronavirus disease 2019 (COVID-19). It is unclear whether such an association is different for various combinations of chronic disease comorbidities. (2) Methods: From 16 March 2020 to 30 November 2021, 104,753 patients with confirmed COVID-19 from Khyber Pakhtunkhwa Province, Pakistan, were studied to determine the association between comorbidities and the duration from symptom onset to death in patients with COVID-19 by stratifying their comorbidity status. (3) Results: The patients with comorbidities had an 84% (OR, 0.16; 95% CI, 0.14 to 0.17) decrease in the duration from symptom onset to death, as opposed to patients without a comorbidity. Among the patients with only one comorbidity, chronic lung disease (OR, 0.06; 95% CI, 0.03 to 0.09) had a greater impact on the duration from symptom onset to death than hypertension (OR, 0.15; 95% CI, 0.13 to 0.18) or diabetes (OR, 0.15; 95% CI, 0.12 to 0.18). The patients with both hypertension and diabetes had the shortest duration (OR, 0.17; 95% CI, 0.14 to 0.20) among the patients with two comorbidities. (4) Conclusions: Comorbidity yielded significant adverse impacts on the duration from symptom onset to death in COVID-19 patients in Pakistan. The impact varied with different combinations of chronic disease comorbidities in terms of the number and type of comorbidities.
]]>Diseases doi: 10.3390/diseases11040174
Authors: Niki Kouna George Noutsos Christina Koufopoulou Dimitrios Panagopoulos Antonis Kattamis
Background: The purpose of this study was to compare the immediate and long-term complications that are associated with the utilized techniques for the insertion of indwelling central venous catheters, that is the open surgical technique, the ultrasound-guided technique, and the transcutaneous technique based on external anatomical landmarks in the right internal jugular vein, to a pediatric population. Methods: This was a prospective randomized trial based on a pediatric patient population under 16 years of age of a tertiary pediatric-oncological hospital. The procedure was performed by a medical team with varying experience regarding the percutaneous and open insertion methods. We studied the outcome of our procedure, based on the immediate and delayed complication rate, as well as the needed time in order to complete the procedure and mean duration of line use. Results: The patients that were inserted in our protocol were divided into three subgroups based on the selected technique for the insertion of the central venous catheter. A total number of 88 insertions (25.4%) (out of 346) were based on the technique that was using external anatomical landmarks, 121 insertions were based on the ultrasound-guided transcutaneous technique (34.9%), whereas in 137 cases (39.5%) the open surgical technique was preferred. All cases that were related to catheter re-insertion were excluded from our study. We performed a statistical analysis regarding the catheter dwell time between the three subgroups of patients and no significant difference was recorded. Moreover, the development of thrombosis was investigated, and we noted that a higher percentage of this complication was related to the transcutaneous external landmark and open surgical technique. Also, the incidence of infection was taken into consideration, which manifested an increased incidence when the transcutaneous technique based on external landmarks was used. Conclusions: Ultrasound-guided percutaneous insertion was considered to be a safe and effective technique for the insertion of central venous catheters. Our study also demonstrated a decrease in operating times when performed by operators with increasing expertise, increased preservation of the diameter of the venous lumen, and no increase in complication rates when the ultrasound-guided technique was selected.
]]>Diseases doi: 10.3390/diseases11040175
Authors: Fabián Alonso Alfaro-Alvarado José Vicente Rosas-Barrientos María Esther Ocharan-Hernández Dylan Díaz-Chiguer Cruz Vargas-De-León
Background: Aging is associated with a decrease in muscle mass. Insulin resistance and hyperglycemia accelerate muscle loss, leading to a deterioration in strength, muscle mass, and physical capacity in older adults. This study was conducted to determine the association between sarcopenia and poor glycemic control in older adults with type 2 diabetes mellitus (T2D). Methods: A cross-sectional study was carried out in older adults with T2D in geriatric outpatient clinics. Sarcopenia was diagnosed as per the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. According to glycosylated hemoglobin (HbA1c) levels, participants were classified into glycemic control (HbA1c ≤ 7.5%) and poor glycemic control (HbA1c ≥ 7.5%) groups. Results: Older adults with sarcopenia were found to have poor glycemic control compared to adults without sarcopenia (62.3% vs. 47.9%, p = 0.007). Logistic regression analysis showed an association between poor glycemic control and the presence of sarcopenia (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.17–2.75) and low muscle mass (OR: 1.73, 95% CI: 1.07–2.73). Conclusions: Poor glycemic control is associated with the presence of sarcopenia and low muscle mass, which highlights the need to implement better treatment strategies in order to reduce the loss of muscle mass.
]]>Diseases doi: 10.3390/diseases11040173
Authors: Ioannis Chrysanthopoulos Anastasios Potiris Eirini Drakaki Despoina Mavrogianni Nikolaos Machairiotis Paul Zarogoulidis Theodoros Karampitsakos Pavlos Machairoudias Dionysios Vrachnis Periklis Panagopoulos Peter Drakakis Sofoklis Stavros
Background: COVID-19 is a modern worldwide pandemic that affected and continues to affect millions of people around the world. Since the discovery that angiotensin-converting enzyme 2 (ACE2) is the binding site for COVID-19 to achieve cell entry, there has been a continuous debate about the effect of COVID-19 infection in first and second trimester abortions. The aim of this review is to investigate the impact of COVID-19 infection on the incidence of miscarriage. Furthermore, we seek to identify potential pathophysiological mechanisms of early pregnancy loss present in infected women. Methods: A literature review was conducted on different databases, including PubMed, Google Scholar, Ovid, Science Direct, Scopus, and Cochrane library, between 1 January 2020 and 31 August 2023. A total of 364 articles were identified and 32 articles were ultimately included in the review. Results: There are several case studies that provide evidence that early pregnancy loss is associated with COVID-19 infection. These findings are not further confirmed by the majority of systematic reviews and meta-analyses, which demonstrate that the total number of miscarriages do not differ significantly between infected and non-infected groups. Furthermore, there are also case reports that associate COVID-19 infection with late second trimester abortions. Conclusions: Given that the virus persists globally, it is important to gain a better understanding of its associated risks in the reproductive process, and larger, more homogeneous, and controlled studies are required to obtain more robust data that can be meta-analyzed to obtain an overview of this potential relationship.
]]>Diseases doi: 10.3390/diseases11040172
Authors: Yuki Daigo Erina Daigo Hiroshi Fukuoka Nobuko Fukuoka Jun Idogaki Yusuke Taniguchi Takashi Tsutsumi Masatsugu Ishikawa Kazuya Takahashi
A number of studies have recently demonstrated the effectiveness of CO2 laser irradiation for the repair and regeneration of scar tissue from injuries or surgical wounds. However, such studies of the oral mucosa are highly limited. Previous studies using CO2 laser irradiation have indicated that two factors contribute to esthetic healing, namely, artificial scabs, which are a coagulated and carbonized blood layer formed on the wound surface, and photobiomodulation therapy (PBMT) for suppressing wound scarring and promoting wound healing. This review outlines basic research and clinical studies of esthetic healing with the use of a CO2 laser for both artificial scab formation by high-intensity laser therapy and PBMT in the treatment of injuries and surgical wounds with small parenchymal defects in oral soft tissues. The results showed that the wound surface was covered by an artificial scab, enabling the accumulation of blood and the perfusion necessary for tissue regeneration and repair. Subsequent PBMT also downregulated the expression of transformation growth factor-b1, which is involved in tissue scarring, and decreased the appearance of myofibroblasts. Taken together, artificial scabs and PBMT using CO2 lasers contribute to the suppression of scarring in the tissue repair process, leading to favorable esthetic and functional outcomes of wound healing.
]]>Diseases doi: 10.3390/diseases11040171
Authors: Davide Ippolito Cesare Maino Davide Gandola Paolo Niccolò Franco Radu Miron Vlad Barbu Marco Bologna Rocco Corso Mihaela Elena Breaban
Background: Considering the large number of patients with pulmonary symptoms admitted to the emergency department daily, it is essential to diagnose them correctly. It is necessary to quickly solve the differential diagnosis between COVID-19 and typical bacterial pneumonia to address them with the best management possible. In this setting, an artificial intelligence (AI) system can help radiologists detect pneumonia more quickly. Methods: We aimed to test the diagnostic performance of an AI system in detecting COVID-19 pneumonia and typical bacterial pneumonia in patients who underwent a chest X-ray (CXR) and were admitted to the emergency department. The final dataset was composed of three sub-datasets: the first included all patients positive for COVID-19 pneumonia (n = 1140, namely “COVID-19+”), the second one included all patients with typical bacterial pneumonia (n = 500, “pneumonia+”), and the third one was composed of healthy subjects (n = 1000). Two radiologists were blinded to demographic, clinical, and laboratory data. The developed AI system was used to evaluate all CXRs randomly and was asked to classify them into three classes. Cohen’s κ was used for interrater reliability analysis. The AI system’s diagnostic accuracy was evaluated using a confusion matrix, and 95%CIs were reported as appropriate. Results: The interrater reliability analysis between the most experienced radiologist and the AI system reported an almost perfect agreement for COVID-19+ (κ = 0.822) and pneumonia+ (κ = 0.913). We found 96% sensitivity (95% CIs = 94.9–96.9) and 79.8% specificity (76.4–82.9) for the radiologist and 94.7% sensitivity (93.4–95.8) and 80.2% specificity (76.9–83.2) for the AI system in the detection of COVID-19+. Moreover, we found 97.9% sensitivity (98–99.3) and 88% specificity (83.5–91.7) for the radiologist and 97.5% sensitivity (96.5–98.3) and 83.9% specificity (79–87.9) for the AI system in the detection of pneumonia+ patients. Finally, the AI system reached an accuracy of 93.8%, with a misclassification rate of 6.2% and weighted-F1 of 93.8% in detecting COVID+, pneumonia+, and healthy subjects. Conclusions: The AI system demonstrated excellent diagnostic performance in identifying COVID-19 and typical bacterial pneumonia in CXRs acquired in the emergency setting.
]]>Diseases doi: 10.3390/diseases11040170
Authors: Diego B. Ortega-Zhindón Nonanzit Pérez-Hernández José Manuel Rodríguez-Pérez José A. García-Montes Juan Calderón-Colmenero Frida Rivera-Buendía Jorge L. Cervantes-Salazar
Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2–9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock–Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.
]]>Diseases doi: 10.3390/diseases11040169
Authors: Martina Pelagalli Flaminia Tomassetti Eleonora Nicolai Alfredo Giovannelli Silvia Codella Mariannina Iozzo Renato Massoud Roberto Secchi Adriano Venditti Massimo Pieri Sergio Bernardini
(1) Background: The erythrocyte sedimentation rate (ESR) is widely diffused in hematology laboratories to monitor inflammatory statuses, response to therapies (such as antibiotics), and oncologic diseases. However, ESR is not a specific diagnostic marker but needs to be contextualized and compared with clinical and other laboratory findings. This study aimed to investigate the performance of two automated instruments, namely the DIESSE CUBE 30 TOUCH (DIESSE, Siena, Italy) and the Alifax Test 1 (Alifax Srl, Polverara, Italy), in comparison with the gold standard, the Westergren method, in lymphoproliferative and myeloproliferative patients. (2) Methods: 97 EDTA samples were selected from the hematology department of Roma Tor Vergata Hospital and analyzed. Statistical analysis was applied. (3) A good correlation between CUBE 30 TOUCH and the gold standard was observed in the overall sample (R2 = 0.90), as well as in patients with lymphoproliferative diseases (R2 = 0.90) and myeloproliferative diseases (R2 = 0.90). The correlation between Test 1 and the gold standard was observed in the overall sample (R2 = 0.68), as well as in patients with lymphoproliferative diseases (R2 = 0.79) and myeloproliferative diseases (R2 = 0.53). (4) Conclusions: The CUBE 30 TOUCH appears to be a more trustworthy tool for evaluating ESR in these pathologies.
]]>Diseases doi: 10.3390/diseases11040168
Authors: Marat V. Ezhov Igor V. Sergienko Sergey M. Kryzhanovskiy Kirill S. Manko Elena V. Timoshina
Background: The objective of this study was to conduct a comparative evaluation of the effectiveness of ezetimibe in combination with statins or statin monotherapy in patients with hypercholesterolemia in a real-world setting. Methods: It was a retrospective multicenter observational study conducted in Russia. We included patients who received statins or a combination of statins with ezetimibe for ≥3 months. The primary endpoint of this study was the frequency of achieving low-density lipoprotein cholesterol (LDL-C) goal levels at the time of enrollment in the study (%). Results: The full analysis set consisted of 1000 patients: 250 subjects in the statin monotherapy group and 750 subjects in the combination group. The groups did not differ in clinical, demographic, or laboratory variables, except for a higher prevalence of hypertension and higher baseline lipid values in the statin monotherapy group. During treatment, the LDL-C concentration decreased by 1.10 ± 1.04 mmol/L (change of −27.5 ± 28.5% from baseline) in the statin monotherapy group and by 1.55 ± 1.17 mmol/L (change of −38.2 ± 25.6% from baseline) in the combination therapy group, p < 0.001. The target LDL-C level was achieved in 22.4% of the patients in the monotherapy group compared with 28.8% of the patients in the combination therapy group, p = 0.049. Conclusions: In real-world clinical practice, statin/ezetimibe combination therapy demonstrated a more frequent achievement of target LDL-C levels compared with statin monotherapy. The addition of ezetimibe to statin therapy increased the probability of achieving LDL-C level goals by 29%.
]]>Diseases doi: 10.3390/diseases11040166
Authors: Chrysoula Taskou Antigoni Sarantaki Vasiliki Georgakopoulou Gerasimos Spyratos Panagiotis Drossos Georgios Daskalakis Apostolos Beloukas Aikaterini Lykeridou
Special populations, particularly pregnant women, are uniquely susceptible to infectious diseases due to alterations in their immunological, respiratory, and cardiovascular systems during gestation. Influenza infections during the perinatal period have been associated with more severe maternal and perinatal outcomes, underscoring the critical importance of vaccination data for pregnant women. According to the World Health Organization (WHO), all pregnant women and those of childbearing age should receive the inactivated influenza vaccine, irrespective of their pregnancy stage. This study aimed to elucidate factors influencing neonatal antibody presence following maternal influenza vaccination. Conducted through convenience sampling in Athens, Greece, this study involved 78 pregnant women who received flu vaccinations. The participants completed questionnaires covering demographics, obstetric history, attitudes toward influenza vaccination, and knowledge about the influenza virus and pregnancy vaccination. Blood samples were collected from 83 neonates to assess IgG antibody presence. Five of the surveyed women had twin pregnancies. The statistical analysis employed IBM SPSS-Statistics version 26.0. This study revealed the presence of positive influenza A and B antibodies in neonates following maternal immunization. Furthermore, it identified factors such as the gestational week and timing of vaccination during pregnancy that influenced the transfer of antibodies from mother to fetus. These findings offer valuable insights for healthcare professionals to provide informed recommendations on influenza vaccination during pregnancy and empower expectant mothers to make informed decisions about the benefits of immunization.
]]>Diseases doi: 10.3390/diseases11040167
Authors: Gioconda Furciniti Giuseppe Casalino Francesco M. Lo Russo Niccolò Bolli Megi Meneri Giacomo P. Comi Stefania P. Corti Daniele Velardo
POEMS syndrome—characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes—is an uncommon and complex paraneoplastic disorder encompassing a diverse array of symptoms. Here we report the challenging case of a 34-year-old female who sought medical attention at the emergency department due to distal lower limb weakness. She was breastfeeding her first child at that time. Her condition rapidly deteriorated, making it difficult for her to perform simple tasks independently. Initially, she struggled with activities like jumping or climbing stairs. Eventually, her ability to walk was also compromised. These symptoms underscored the swift evolution of her polyneuropathy. Nerve conduction studies and electromyography confirmed a diagnosis of mixed demyelinating and axonal polyneuropathy. Subsequent investigations, including bone marrow biopsy and immunochemistry testing, revealed a plasma cell disorder characterized by lambda monoclonal gammopathy, along with elevated levels of vascular endothelial growth factor (VEGF > 8000 pg/mL). This pivotal finding led to the diagnosis of POEMS syndrome, prompting the initiation of antineoplastic therapy (daratumumab-lenalidomide-dexamethasone) to manage this condition. An autologous cell transplantation was planned. The rarity of POEMS syndrome and its diverse clinical manifestations often lead to an incorrect or delayed diagnosis. Our case underscores the importance of considering this syndrome in patients presenting with acute or subacute polyneuropathy, even if the patients are young. In conclusion, this case elucidates the diagnostic complexities of POEMS syndrome, emphasizing the integral role of comprehensive multidisciplinary evaluations and the potential influence of increased VEGF as a diagnostic key element and possible therapeutic target.
]]>Diseases doi: 10.3390/diseases11040165
Authors: Eleni Pavlidou Sousana K. Papadopoulou Georgios Antasouras Theofanis Vorvolakos Olga Alexatou Gerasimos Tsourouflis Exakousti-Petroula Angelakou Aspasia Serdari Maria G. Grammatikopoulou Evmorfia Psara Konstantinos Vadikolias Antonios Dakanalis Nikolaos Lefantzis Constantinos Giaginis
Background: The COVID-19 pandemic has led to unfavorable disruptions to daily living routines by exerting deleterious effects on several aspects of human mental and physical health and quality of life worldwide. The purpose of the current survey is to explore the potential association of COVID-19 infection with multiple sociodemographic, anthropometric, and lifestyle factors of community-dwelling older adults. Methods: This is a cross-sectional survey including 5197 older adults aged over 65 years old from 10 geographically diverse regions of Greece. Relevant questionnaires were used to record study the population sociodemographic factor, while anthropometric parameters were also measured. Validated questionnaires were also applied to assess several lifestyle factors such as depression, anxiety, stress, cognitive status, sleep quality, health-related quality of life, physical activity levels, and Mediterranean diet (MD) adherence. Results: In multivariate regression analysis, COVID-19 infection was significantly, independently related with urban residence (p = 0.0107), regular smoking (p = 0.0218), overweight status and obesity (p = 0.0036), as well as abdominal obesity (p = 0.0008), higher risk of depression (p = 0.0027), anxiety (p = 0.0045), stress (p = 0.0038), inadequate sleep quality (p = 0.0108), lower physical activity levels (p = 0.0012), reduced MD compliance (p = 0.0009), and poor health-related quality of life (p = 0.0002). In univariate analysis, older adults’ age (p = 0.0001), male gender (p = 0.0015), living alone (p = 0.0023), lower educational and economic level (p = 0.0175 and p = 0.0294, respectively), and cognition decline (p = 0.0032) were also related with the presence of COVID-19 infection; however, these associations were considerably attenuated at a non-significant level by adjustment for several confounders in multivariate analysis. Conclusions: This is one of the few available studies supporting evidence that COVID-19 infection may be associated with diverse sociodemographic, anthropometric, and lifestyle factors in an older adults’ population in Greece. This study highlights the strong demand to provide psychological and nutritional counselling and support to older adults diagnosed with COVID-19 infection in order to ameliorate disease symptoms and severity, emphasizing the adaptation of healthy dietary and lifestyle habits as preventing and supplementary therapeutic factors against COVID-19.
]]>Diseases doi: 10.3390/diseases11040164
Authors: Kristína Macáková Mária Tekeľová Vanda Mlynáriková Katarína Šebeková Barbora Vlková Peter Celec Emöke Šteňová
Rheumatoid arthritis (RA) is associated with high cardiovascular mortality. It is not clear whether the metabolic consequences of chronic inflammation are involved. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are highly efficient in the treatment of inflammation in RA. In this study, we aimed to describe the metabolic effects of anti-TNF-α treatment in RA patients. The clinical status of 16 patients was assessed using disease activity score-28 (DAS28) and C-reactive protein (CRP). Plasma samples were collected before treatment with anti-TNF-α treatment as well as after three and six months of treatment. Markers of lipid and glucose metabolism, as well as renal biomarkers, were assessed using standard biochemistry. ELISA was used for the quantification of insulin, leptin, and adiponectin. Although fasting insulin decreased by 14% at the end of the study, most of the analyzed parameters did not show any statistically or clinically significant dynamics. The exception was total bilirubin and cholesterol, which increased by 53% and 14%, respectively, after six months of treatment with anti-TNF-α treatment. Anti-TNF-α treatment did not induce major metabolic changes despite the strong anti-inflammatory and clinical symptoms of RA. Further studies will show whether longer observations are required for the detection of the metabolic effects of the anti-inflammatory treatment. Additional research is needed to understand the observed effect of bilirubin as an important endogenous antioxidant.
]]>Diseases doi: 10.3390/diseases11040163
Authors: Juan Carlos Sánchez-García Andrés Reinoso-Cobo Beatriz Piqueras-Sola Jonathan Cortés-Martín María José Menor-Rodríguez Raquel Alabau-Dasi Raquel Rodríguez-Blanque
Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, “brain fog”, respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies.
]]>Diseases doi: 10.3390/diseases11040162
Authors: Walter Belda Luiz Felipe Domingues Passero Caroline Heleno Chagas de Carvalho Paula Celeste Rubiano Mojica Pablo Andrade Vale
Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient’s quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.
]]>Diseases doi: 10.3390/diseases11040161
Authors: Veroniki Komninaka Pagona Flevari Georgios Karkaletsis Theodoros Androutsakos Theofili Karkaletsi Ioannis Ntanasis-Stathopoulos Evaggelia-Eleni Ntelaki Evangelos Terpos
We describe two cases of thalassemia intermedia (TI) patients with the presence of Gaucher-like cells in hematopoietic tissue biopsies, raising diagnostic dilemmas. The first is a 56-year-old female with bone lesions, splenomegaly, hypochromic microcytic anemia and Gaucher-like cells in the bone marrow, with a final diagnosis of TI, and the second is a 69-year-old male with TI, monoclonal gammopathy of undetermined significance (MGUS) that accelerated to multiple myeloma (MM) requiring treatment, bone disease and Gaucher-like cells in the bone marrow and the spleen, and heterozygoty of Gaucher disease (GD). Gaucher-like cells are difficult to differentiate from true Gaucher cells, that are the hallmark of GD suspicion. These cells are usually reported in the lymphohematopoietic system. They have been described in myeloproliferative disorders, hematological malignancies, infectious diseases, hemoglobinopathies and other hemolytic anemias. The presence of Gaucher-like cells in patients with thalassemia major has been well documented, whereas there are limited references regarding cases with thalassemia intermedia. The identification of these cells in thalassemia probably reflects the high cell turnover. The bony complications in GD and TIare not yet fully explained in the literature, and this raises the question of whether Gaucher-like cells could play a pathogenetic role in the bone disease of thalassemia, as Gaucher cells are considered to play a similar role in bone complications of GD. Moreover, given the rarity and similarity of Gaucher and Gaucher-like cells, we would like to highlight that the presence of Gaucher-like cells in the bone marrow should not be overlooked, as they might be obscuring an underlying pathology, in order to ensure that hematologists, internists and hematopathologists will be promptly and accurately diagnosed.
]]>Diseases doi: 10.3390/diseases11040160
Authors: Eduardo Hernández-Cuellar Kohsuke Tsuchiya Ricardo Valle-Ríos Oscar Medina-Contreras
Staphylococcus aureus (S. aureus) is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections. Methicillin-resistant S. aureus (MRSA) strains are associated with more serious infections and higher mortality rates and are more complex in terms of antibiotic resistance. It is still controversial whether MRSA are indeed more virulent than methicillin-susceptible S. aureus (MSSA) strains. A difference in biofilm formation by both types of bacteria has been suggested, but how only the presence of the SCCmec cassette or mecA influences this phenotype remains unclear. In this review, we have searched for literature studying the difference in biofilm formation by MRSA and MSSA. We highlighted the relevance of the icaADBC operon in the PIA-dependent biofilms generated by MSSA under osmotic stress conditions, and the role of extracellular DNA and surface proteins in the PIA-independent biofilms generated by MRSA. We described the prominent role of surface proteins with the LPXTG motif and hydrolases for the release of extracellular DNA in the MRSA biofilm formation. Finally, we explained the main regulatory systems in S. aureus involved in virulence and biofilm formation, such as the SarA and Agr systems. As most of the studies were in vitro using inert surfaces, it will be necessary in the future to focus on biofilm formation on extracellular matrix components and its relevance in the pathogenesis of infection by both types of strains using in vivo animal models.
]]>Diseases doi: 10.3390/diseases11040159
Authors: Kainat Riaz Sejal Suneel Mohammad Hamza Bin Abdul Malik Tooba Kashif Irfan Ullah Abdul Waris Marco Di Nicola Marianna Mazza Gabriele Sani Giovanni Martinotti Domenico De Berardis
Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the “breakthrough therapy” designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.
]]>Diseases doi: 10.3390/diseases11040158
Authors: Chrysoula Giourga Sousana K. Papadopoulou Gavriela Voulgaridou Calliope Karastogiannidou Constantinos Giaginis Agathi Pritsa
A balanced diet is achieved not only via the consumption of a variety of food products but also by ensuring that we take in sufficient quantities the micronutrients necessary for the adequate functioning of the human body, such as vitamins, an important one of which is vitamin D. Vitamin D has been closely linked to bone health. Vitamin D deficiency has often been associated with negative effects concerning several pregnancy adverse outcomes, the most important of which are the birth of SGA newborns, premature birth, and, finally, preeclampsia, which are discussed in this work. The aim of this review is to critically summarize and scrutinize whether the concentration of vitamin D in the blood serum of pregnant women in all its forms may be correlated with the risk of preeclampsia during pregnancy and whether vitamin D levels could act both as a protective agent or as a risk factor or even a prognostic measure of the disease. The association of vitamin D levels with the onset of preeclampsia was examined by searching the PubMed and Google Scholar databases. A total of 31 clinical trials were identified and included in this review, with the aim of summarizing the recent data concerning vitamin D levels and the risk of preeclampsia. Among them, 16 were published in the last five years, and 13 were published within the last a decade. Most studies showed a significant association between vitamin D deficiency and preeclampsia risk. It was also found that the higher the dose, the lower the risk of disease. Of the 31 articles, only 7 of them did not show a significant difference between vitamin D levels and preeclampsia regardless of comorbidity. The results of this review suggest that there is indeed an association between the concentration of vitamin D during pregnancy and the risk of preeclampsia; however, further studies are strongly recommended to derive conclusive evidence.
]]>Diseases doi: 10.3390/diseases11040157
Authors: Christos Tsagkaris Hamayle Saeed Lily Laubscher Anna Eleftheriades Sofoklis Stavros Eirini Drakaki Anastasios Potiris Dimitrios Panagiotopoulos Dimos Sioutis Periklis Panagopoulos Ahsan Zil-E-Ali
Surgery is one of the most energy-intensive branches of healthcare. Although the COVID-19 pandemic has reduced surgical volumes, infection control protocols have increased the ecological footprint of surgery owing to the extensive use of personal protective equipment, sanitation, testing and isolation resources. The burden of environmental diseases requiring surgical care, the international commitment towards environmental sustainability and the global efforts to return to the pre-pandemic surgical workflow call for action towards climate-friendly surgery. The authors have searched the peer-reviewed and gray literature for clinical studies, reports and guidelines related to the ecological footprint of surgical care and the available solutions and frameworks to reduce it. Numerous studies concede that surgery is associated with a high rate of energy utilization and waste generation that is comparable to major non-medical sources of pollution. Recommendations and research questions outlining environmentally sustainable models of surgical practices span from sanitation and air quality improvement systems to the allocation of non-recyclable consumables and energy-efficient surgical planning. The latter are particularly relevant to infection control protocols for COVID-19. Paving the way towards climate-friendly surgery is a worthy endeavor with a major potential to improve surgical practice and outcomes in the long term.
]]>Diseases doi: 10.3390/diseases11040156
Authors: Maria V. Kuznetsova Narine M. Tonoyan Elena V. Trubnikova Dmitry V. Zelensky Ksenia A. Svirepova Leila V. Adamyan Dmitry Y. Trofimov Gennady T. Sukhikh
Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.
]]>Diseases doi: 10.3390/diseases11040155
Authors: Julyane N. S. Kaihara Caroline K. Minami Maria T. S. Peraçoli Mariana Romão-Veiga Vanessa R. Ribeiro-Vasques José C. Peraçoli Ana C. T. Palei Ricardo C. Cavalli Priscila R. Nunes Marcelo R. Luizon Valeria C. Sandrim
Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman’s or Pearson’s tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = −0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.
]]>Diseases doi: 10.3390/diseases11040154
Authors: Abdulaziz Yahya Sharahili Shabir Ahmad Mir Sahar ALDosari Md Dilshad Manzar Bader Alshehri Ayoub Al Othaim Fayez Alghofaili Yahya Madkhali Kamal Shaker Albenasy Jazi S. Alotaibi
Introduction: Type 2 diabetes mellitus (T2DM) patients are at high risk of dyslipidemia, which in turn is associated with macrovascular diseases, such as heart diseases and stroke, and microvascular diseases, such as neuropathy and nephropathy. There are contradictory findings in the literature regarding the relationship between glycated hemoglobin (HbA1c) and the lipid profile among T2DM patients. This study was performed to investigate the association between HbA1c level and the lipid profile in elderly T2DM patients at a primary care hospital in Jeddah City, Saudi Arabia. Methods: This study is a retrospective cross-sectional study conducted at the Prince Abdul Majeed Healthcare Center (PAMHC) in Jeddah, Saudi Arabia. The sociodemographic and clinical data of the T2DM patients who had visited the PAMHC from 1 January 2020 to 31 December 2021, were collected from the data registry of the PAMHC and analyzed for publication. Results: The study included a total of 988 T2DM patients (53.3% male). Of the participants, 42.9% were aged between 55 and 64 years. Dyslipidemia parameters were presented as high LDL-c (in 60.3% cases), low HDL-c (in 39.8% cases), high triglycerides (in 34.9% cases), and high total cholesterol (in 34.8% cases). The correlation of HbA1c with total cholesterol (TC) and triglycerides (TGs) was positively significant, thereby highlighting the important link between glycemic control and dyslipidemia. A mean increase of 4.88 mg/dL and 3.33 mmHg in TG level and diastolic blood pressure, respectively, was associated with the male gender, in comparison to the female gender. However, the male gender was significantly associated with the reduction in the mean cholesterol level, BMI, HbA1c, HDL-c, and LDL-c by 11.49 mg/dL, 1.39 kg/m2, 0.31%, 7.47 mg/dL, and 5.6 mg/dL, respectively, in comparison to the female gender. Conclusions: The results of this study show that HbA1c was significantly associated with cholesterol and triglyceride levels in the T2DM patients included in the study. Our findings highlight the important relationship between glycemic control and dyslipidemia.
]]>Diseases doi: 10.3390/diseases11040153
Authors: Gabriel Mazón-Ortiz Galo Cerda-Mejía Eberto Gutiérrez Morales Karel Diéguez-Santana Juan M. Ruso Humberto González-Díaz
Leishmaniasis is a neglected tropical illness with a wide variety of clinical signs ranging from visceral to cutaneous symptoms, resulting in millions of new cases and thousands of fatalities reported annually. This article provides a bibliometric analysis of the main authors’ contributions, institutions, and nations in terms of productivity, citations, and bibliographic linkages to the application of nanoparticles (NPs) for the treatment of leishmania. The study is based on a sample of 524 Scopus documents from 1991 to 2022. Utilising the Bibliometrix R-Tool version 4.0 and VOSviewer software, version 1.6.17 the analysis was developed. We identified crucial subjects associated with the application of NPs in the field of antileishmanial development (NPs and drug formulation for leishmaniasis treatment, animal models, and experiments). We selected research topics that were out of date and oversaturated. Simultaneously, we proposed developing subjects based on multiple analyses of the corpus of published scientific literature (title, abstract, and keywords). Finally, the technique used contributed to the development of a broader and more specific “big picture” of nanomedicine research in antileishmanial studies for future projects.
]]>Diseases doi: 10.3390/diseases11040152
Authors: Kazunori Nakamura Yukio Fujita Hao Chen Kohei Somekawa Fumihiro Kashizaki Harumi Koizumi Kenichi Takahashi Nobuyuki Horita Yu Hara Shigeo Muro Takeshi Kaneko
Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were −0.50 (95% CI: −0.81, −0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George’s Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of −4.42 (95% CI: −9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.
]]>Diseases doi: 10.3390/diseases11040151
Authors: Hollie Saunders Subekshya Khadka Rabi Shrestha Arvind Balavenkataraman Alexander Hochwald Colleen Ball Scott A. Helgeson
Ventilator-associated pneumonia (VAP) has significant effects on patient outcomes, including prolonging the duration of both mechanical ventilation and stay in the intensive care unit (ICU). The aim of this study was to assess the association between non-invasive ventilation/oxygenation (NIVO) prior to intubation and the rate of subsequent VAP. This was a multicenter retrospective cohort study of adult patients who were admitted to the medical ICU from three tertiary care academic centers in three distinct regions. NIVO was defined as continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or high-flow nasal cannula (HFNC) for any duration during the hospitalization prior to intubation. The primary outcome variable was VAP association with NIVO. A total of 17,302 patients were included. VAP developed in 2.6% of the patients (444/17,302), 2.3% (285/12,518) of patients among those who did not have NIVO, 1.6% (30/1879) of patients who had CPAP, 2.5% (17/690) of patients who had HFNC, 8.1% (16/197) of patients who had BiPAP, and 4.8% (96/2018) of patients who had a combination of NIVO types. Compared to those who did not have NIVO, VAP was more likely to develop among those who had BiPAP (adj OR 3.11, 95% CI 1.80–5.37, p < 0.001) or a combination of NIVO types (adj OR 1.91, 95% CI 1.49–2.44, p < 0.001) after adjusting for patient demographics and comorbidities. The use of BiPAP or a combination of NIVO types significantly increases the odds of developing VAP once receiving IMV.
]]>Diseases doi: 10.3390/diseases11040150
Authors: Ana P. B. Silva Cesar Augusto Roque-Borda Christian S. Carnero Canales Laura Maria Duran Gleriani Primo Isabel C. Silva Camila M. Ribeiro Marlus Chorilli Patrícia Bento da Silva Joás L. Silva Fernando Rogério Pavan
The search for new antimicrobial agents is a continuous struggle, mainly because more and more cases of resistant strains are being reported. Mycobacterium tuberculosis (MTB) is the main microorganism responsible for millions of deaths worldwide. The development of new antimicrobial agents is generally aimed at finding strong interactions with one or more bacterial receptors. It has been proven that bacteriophages have the ability to adhere to specific and selective regions. However, their transport and administration must be carefully evaluated as an excess could prevent a positive response and the bacteriophages may be eliminated during their journey. With this in mind, the mycobacteriophage D29 was encapsulated in nanoliposomes, which made it possible to determine its antimicrobial activity during transport and its stability in the treatment of active and latent Mycobacterium tuberculosis. The antimicrobial activity, the cytotoxicity in macrophages and fibroblasts, as well as their infection and time–kill were evaluated. Phage nanoencapsulation showed efficient cell internalization to induce MTB clearance with values greater than 90%. Therefore, it was shown that nanotechnology is capable of assisting in the activity of degradation-sensitive compounds to achieve better therapy and evade the immune response against phages during treatment.
]]>Diseases doi: 10.3390/diseases11040149
Authors: Jihoon Kim Dong Il Gwon Yonghun Kim Gun Ha Kim Seong Ho Kim Hee Ho Chu Jin Hyoung Kim Ji Hoon Shin Gi-Young Ko Hyun-Ki Yoon
This study investigates the clinical and pathological outcomes of preoperative balloon-occluded transcatheter arterial chemoembolization (B-TACE) in patients with single hepatocellular carcinoma (HCC). The data are from 25 consecutive patients who underwent sequential treatment of subsegmental B-TACE and hepatic surgery for single HCC. Radiological and pathological evaluation of oily subsegmentectomy, defined as the iodized oil-laden necrotic area that includes the entire HCC and surrounding liver parenchyma, were performed. Subsegmental B-TACE was technically successful in all patients. The major and minor complication rates were 8% and 24%, respectively. On the first follow-up computed tomography (CT), oily subsegmentectomy was observed in 18 (72%) out of 25 patients. Apart from one patient showing a partial response, the remaining 24 (96%) patients showed a complete response. Pathological complete necrosis of the HCC was observed in 18 (72%) out of 25 patients with complete or extensive necrosis of the peritumoral liver parenchyma. The remaining seven patients without peritumoral parenchymal necrosis had extensive necrosis of the HCCs. In conclusion, preoperative B-TACE can be a safe and effective method for the treatment of single HCC and a good bridge treatment for subsequent surgical resection. In addition, oily subsegmentectomy itself on the CT can be a good predictor of pathological complete necrosis of the HCC. The findings obtained from this study would provide a potential role of B-TACE in the treatment strategy for single HCC.
]]>Diseases doi: 10.3390/diseases11040148
Authors: Noor Alrushaid Firdos Alam Khan Ebtesam Al-Suhaimi Abdelhamid Elaissari
Worldwide, colon cancer is the third most frequent malignancy and the second most common cause of death. Although it can strike anybody at any age, colon cancer mostly affects the elderly. Small, non-cancerous cell clusters inside the colon, commonly known as polyps, are typically where colon cancer growth starts. But over time, if left untreated, these benign polyps may develop into malignant tissues and develop into colon cancer. For the diagnosis of colon cancer, with routine inspection of the colon region for polyps, several techniques, including colonoscopy and cancer scanning, are used. In the case identifying the polyps in the colon area, efforts are being taken to surgically remove the polyps as quickly as possible before they become malignant. If the polyps become malignant, then colon cancer treatment strategies, such as surgery, chemotherapy, targeted therapy, and immunotherapy, are applied to the patients. Despite the recent improvements in diagnosis and prognosis, the treatment of colorectal cancer (CRC) remains a challenging task. The objective of this review was to discuss how CRC is initiated, and its various developmental stages, pathophysiology, and risk factors, and also to explore the current state of colorectal cancer diagnosis and treatment, as well as recent advancements in the field, such as new screening methods and targeted therapies. We examined the limitations of current methods and discussed the ongoing need for research and development in this area. While this topic may be serious and complex, we hope to engage and inform our audience on this important issue.
]]>Diseases doi: 10.3390/diseases11040147
Authors: Khalid Alhazzani Abdullah Almangour Abdulaziz Alsalem Mohammed Alqinyah Abdullah S. Alhamed Hussain N. Alhamami Ahmed Z. Alanazi
Background: Dasatinib, nilotinib, and sorafenib are clinically proven tyrosine kinase inhibitors (TKIs) used for the treatment of leukemia and hepatocellular carcinoma. However, there is a growing concern regarding cardiotoxicity associated with their use. The impact of these TKIs on vascular smooth muscle cells (VSMCs) remains unexplored. This study aims to investigate the effects of TKIs on VSMC proliferation and migration, as well as to elucidate the underlying mechanisms involving inflammatory and apoptotic pathways. Methods: VSMCs were extracted from albino rats and cultured in vitro. The cells were divided into four experimental groups: control, dasatinib, sorafenib, and nilotinib. The MTT assay was employed to assess the cytotoxic effects of TKIs on VSMCs. A scratch assay was conducted to evaluate the inhibitory potential of TKIs on VSMC migration. Flow cytometry analysis was used to detect apoptotic cells. Real-Time PCR expression was utilized to determine the differential gene expression of apoptotic and inflammatory markers. Results: Dasatinib, nilotinib, and sorafenib demonstrated significant inhibitory effects on VSMC viability and migration at low concentrations (<1 µmol/L, p < 0.05). Furthermore, gene expression analysis revealed up-regulation of inflammatory biomarkers (TNF-α, IL-6, and IL-1β) and apoptotic markers (P53, BAX), along with down-regulation of the anti-apoptotic biomarker BCL-2 in response to all TKIs. Conclusions: This study demonstrates that dasatinib, nilotinib, and sorafenib inhibit VSMC proliferation and migration, suggesting their potential to induce vascular injury and remodeling by activating inflammation and apoptosis pathways. These findings highlight the need for further investigation into the cardiotoxic effects of these TKIs and the development of strategies to mitigate their adverse vascular effects.
]]>Diseases doi: 10.3390/diseases11040146
Authors: Prashant Sakharkar Sonali Kurup
The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors searched databases such as PubMed, Medline, Scopus, and Cochrane Central Register of Controlled Trials for randomized control trials (RCTs) comparing erlotinib plus bevacizumab with erlotinib in NSCLC patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were the outcomes of interest. The pooled hazard ratio (HR) and relative risk (RR) were estimated utilizing both fixed- and random-effect models. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Nine studies comprising 1698 patients with NSCLC were included in this meta-analysis, of whom 850 were treated with erlotinib plus bevacizumab, and 848 with erlotinib. The erlotinib plus bevacizumab combination significantly prolonged PFS (HR, 0.62, 95% CI: 0.56, 0.70, p < 0.00001) but did not show any significant improvement in OS (HR, 0.95; 95% CI: 0.83, 1.07, p = 0.39) and ORR (HR, 1.10; 95% CI: 0.98, 1.24, p = 0.09). Increased risks of hypertension (RR, 5.15; 95% CI: 3.59, 7.39; p < 0.00001), proteinuria (RR, 10.54; 95% CI: 3.80, 29.20; p < 0.00001) and grade 3 and higher AEs (RR, 2.09; 95% CI: 1.47, 2.97; p < 0.00001) were observed with the erlotinib-plus-bevacizumab combination compared to erlotinib monotherapy. On subgroup analyses, the erlotinib plus bevacizumab combination improved PFS only. Combining erlotinib and bevacizumab has been shown to improve PFS in advanced NSCLC patients but did not show any significant OS and ORR benefits. Furthermore, risks of hypertension, proteinuria, and grade 3 or higher AEs were greater with the erlotinib-and-bevacizumab combination.
]]>Diseases doi: 10.3390/diseases11040145
Authors: Olga I. Afanasieva Alexandra V. Tyurina Marat V. Ezhov Oxana A. Razova Elena A. Klesareva Sergei N. Pokrovsky
Background. Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD). Methods. In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained. Results. The patients were divided into two groups depending on the presence of a low- (LMW, n = 52) or high-molecular weight (HMW, n = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), p = 0.03), but not elevated Lp(a) (1.9 (0.8–4.6), p = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients. Conclusion. The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.
]]>Diseases doi: 10.3390/diseases11040144
Authors: Cecilia Salzillo Andrea Quaranta Giovanni De Biasi Gerardo Cazzato Gabriella Serio Antonella Vimercati Pierpaolo Nicolì Leonardo Resta Andrea Marzullo
A teratoma is a neoplasm composed of cell populations or tissues that are reminiscent, in their appearance, of normal elements derived from at least two embryonic layers. Fetal mature teratomas are normally benign, cystic, and typically occur along the midline, while they are rare in the posterior mediastinum. Teratomas are frequently solitary; however, they may sometimes be associated with other congenital anomalies and/or with chromosomal abnormalities. Clinically, they are often asymptomatic but can occasionally cause compression symptoms. Prenatal diagnoses are uncommon and made with ultrasonography; differential diagnosis with other congenital conditions is mandatory. We report the case of a 21 weeks of gestational age old fetus with a mature triphyllic fetal cystic teratoma, grade 0, located in the right posterior mediastinum. The tumor presented as a 3 cm wide cystic mass that caused a contralateral shift of the surrounding structures. Histological examination later revealed the presence of derivatives of the three germ layers, such as hyaline cartilage, smooth muscle, nervous tissue, and a respiratory-type epithelium.
]]>Diseases doi: 10.3390/diseases11040143
Authors: Leonardo Tomei Francesca Saretta Stefania Arasi Lucrezia Sarti Amelia Licari Mattia Giovannini Simona Barni Giulia Liccioli Valeria Tallarico Alessandra Piccorossi Carlo Caffarelli Elio Novembre Francesca Mori
Chronic urticaria (CU) is one of the most common skin disorders worldwide. Among the inducible subgroup of CU, cold urticaria (ColdU) can affect both children and adults and is the only type associated with the risk of anaphylaxis without cofactors. In the scientific literature, data about cold anaphylaxis (ColdA) are poor, especially at pediatric age, and little is known about risk factors associated with the onset of systemic reactions and about the criteria for prescribing adrenaline auto-injectors (AAIs) in these patients. We describe the clinical characteristics and management of a case series of 21 patients with a history of ColdA, and we compare them with the pediatric case reports and case series published so far. On the basis of the scientific literature and of our case series of patients, we suggest that AAI should be prescribed to all high-risk patients: those with urticaria caused by cold-water immersion, oropharyngeal reactions, and with a previous history of systemic symptoms or anaphylaxis.
]]>Diseases doi: 10.3390/diseases11040142
Authors: Rafael Saperstein Sanjay Goel Radhashree Maitra
Purpose: To investigate the alterations in the expression of noncoding, micro, and small RNA expression during treatment with oncolytic reovirus in KRAS-mutated colorectal cancer. Methods: Oncolytic reovirus treatment was administered in phase 1 clinical trial (NCT01274624) for 5 days every 28 days, and blood samples were collected before the administration of the reovirus and 48 h, 8 days, and 15 days after its administration on day 1. Data from the blood samples were sorted using Transcriptome Analysis Software (TAC) 4.0, where a two-tailed t-test and a fold change filter were used to ascertain which sample signals had a statistically significant relative fold change of greater than 2 at multiple timepoints before or after oncolytic reovirus administration. Results: The long noncoding RNA’s RP11-332M2.1 (−6.1 x), LINC01506 (−16.18 x), and LINC00534 (−1.94 x) were downregulated at 48 h after reovirus administration [p < 0.05]. ncRNA’s EPB41L4A-AS1 (−6.34 x, 48 h; 11.99 x, day 8), JAK2 (2.2 x, 48 h; −2.23 x, day 8), ANXA4 (20.47 x, day 8; −7.54 x, day 15), and PCDH9 (−2.09, day 8; 1.82 x, day 15) were affected by the reovirus treatment and reflected the progress of the treatment [p < 0.05]. The small RNA SNORA26 (−1.59 x, day 8) was downregulated 48 h after the reovirus administration [p < 0.05]. The microRNA MIR-4461 (6.18 x, day 8; −3.76 x, day 15) was also affected by the reovirus administration [p < 0.05]. Conclusion: The administration of oncolytic reovirus to treat KRAS-mutated colorectal cancer is reflected in a noncoding RNA profile, and expression levels of the ncRNAs in that profile may thus be able to be used as a potential predictive marker for reovirus-treated colorectal cancer.
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