Diseases, Volume 12, Issue 1 (January 2024) – 29 articles

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. Full article

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. Full article

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. Full article

(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. Full article

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. Full article

(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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

(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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article