Diseases, Volume 12, Issue 12 (December 2024) – 41 articles

Background: Iron deficiency (ID) often coexists with heart failure (HF), and its prevalence increases with the severity of HF. Intravenous ferric carboxymaltose (FCM) has been associated with improvements in clinical outcomes, functional capacity, and quality of life (QoL) in patients with HF and ID. However, while earlier studies showed favorable results, more recent studies have failed to demonstrate significant improvements in outcomes for patients with heart failure with reduced ejection fraction (HFrEF) and ID. This meta-analysis seeks to provide updated insights into the effectiveness and safety of FCM compared to placebo/standard of care (SoC) among patients with HFrEF and ID/iron deficiency anemia (IDA). Methods: We performed a systematic review and meta-analysis of the literature from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. A statistical analysis was carried out using RevMan 5.4 with a random-effects model. Dichotomous outcomes were reported as odds ratios (OR), while continuous outcomes were presented as the weighted mean difference (WMD) with corresponding 95% confidence intervals (CI), and heterogeneity was assessed using the I² test. Results: The final analysis included data from six randomized controlled trials (RCTs), comprising 5132 patients. Our findings indicate a significant reduction in total HF hospitalizations among patients with HFrEF and ID/IDA treated with FCM compared to those receiving the placebo or SoC, with an OR of 0.59 (95% CI: 0.40 to 0.88, p < 0.010). However, no statistically significant difference was observed in the total number of deaths between the FCM and placebo/SoC groups (OR: 0.85; 95% CI: 0.70 to 1.03, p = 0.09), non-HF hospitalizations (OR: 0.71; 95% CI: 0.41 to 1.25, p = 0.24), or the composite outcome of cardiovascular hospitalizations and cardiovascular deaths (OR: 0.65; 95% CI: 0.40 to 1.04, p = 0.07). Regarding functional capacity, as assessed by the change in 6-min walk test (6MWT) distance, no significant improvement was found, with a weighted mean difference (WMD) of 14.03 (95% CI: −10.94 to 38.99, p = 0.27). QoL, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, also did not show significant enhancement, with a WMD of 3.85 (95% CI: −0.55 to 8.24, p = 0.09). Furthermore, the safety analysis revealed no significant difference in the incidence of serious adverse events between the FCM and placebo/SoC groups, with an OR of 0.73 (95% CI: 0.49 to 1.10, p = 0.13). Conclusions: In patients with HFrEF and IDA, treatment with intravenous FCM significantly lowers the risk of total HF hospitalizations but does not appear to affect functional capacity, QoL, or mortality. Full article

Background: Monitoring of measurable residual disease (MRD) requires highly sensitive flow cytometry protocols to provide an accurate prediction of shorter progression-free survival. High assay sensitivity generally requires rapid processing to avoid cell loss from small bone marrow sample volumes, but this requirement conflicts with the need in most clinical cytometry laboratories for long processing and acquisition times, especially when multiple MRD studies coincide on the same day. Methods: The proposed protocol was applied to 226 human bone marrow and 45 peripheral blood samples submitted for the study of MRD or the detection of rare cells. Samples were processed within 24 h of extraction and acquired with an eight-color flow cytometer. Results: The FACSLyse-Bulk protocol allows for the labelling of millions of cells in under 90 min in small sample volumes without affecting the FSC/SSC pattern or antigen expression, and it also allows antigens to be fixed to the membrane, thus avoiding the capping phenomenon. Conclusions: The proposed protocol would allow clinical flow cytometry laboratories to perform MRD studies in house and easily achieve a limit of detection and limit of quantification <0.001%, thus avoiding the need to outsource analysis to specialized cytometry laboratories. Full article

Background: Coronavirus Disease 2019 (COVID-19), triggered by SARS-CoV-2, has represented a global pandemic associated with an elevated rate of mortality, mainly among older individuals. The extensive pulmonary involvement by the viral infection might have precipitated pre-existing chronic conditions in this vulnerable population, including heart failure (HF). Materials and methods: The aim of this retrospective, observational study was to assess the impact of COVID-19 in patients with a prior diagnosis of HF referred to the Emergency Department of the Agostino Gemelli University Hospital between March 2020 and January 2023. A total of 886 HF patients (444 men and 442 women, mean age of 80 ± 10 years) were identified. Patients were matched in a 1:1 ratio by gender, age, number of comorbidities (excluding HF), and vaccination status, using a propensity score matching (PSM) procedure. We compared the outcomes of 189 patients with a concomitant diagnosis of HF with those of 189 matched controls without HF. Results: Among patients with HF, there was a significantly higher prevalence of valvular disease (p = 0.004), atrial fibrillation (p = 0.003), use of anticoagulants (p = 0.001), chronic obstructive pulmonary diseases (p = 0.03), and chronic kidney disease (p = 0.001). In contrast, hypertension was more prevalent among controls than HF patients (p = 0.04). In addition, controls exhibited higher lymphocytes counts and a higher PaO₂/FiO₂ ratio compared to HF patients. During hospitalization, patients with HF were more frequently treated with high-flow nasal cannulas (p = 0.01), required more frequent admission to an intensive care unit (ICU) (p = 0.04), and showed a significantly higher mortality rate (p 0.0001) than controls. Conclusions: HF is an independent risk factor for ICU admission and death in COVID-19 patients. Full article

Background: The term “fetal programming” refers to the effects of endogenous and exogenous corticosteroids, whether received from the mother or the fetus, on brain development and the hypothalamic–pituitary–adrenal axis reset. The authors of this narrative review examine the WHO’s guidelines for prenatal corticosteroids in pregnant women who are at high risk of premature delivery. These guidelines are regarded as the best available for preventing late-life problems resulting from preterm. Methods: In order to find full-text publications published in peer-reviewed journals between 1990 and 2023 that were written in English, the authors searched PubMed, Scopus, Cochrane Library, and Web of Science. Results: The authors highlight the possible adverse long-term effects of prenatal corticosteroid medication on human brain development and function. This pharmacological feature is therapeutically significant because there is less evidence in the scientific literature regarding the potential role that the timing, mode, and dosage of exogenous steroid treatment may have in neurological illnesses down the road. Conclusions: The authors expect that these studies will shed light on the relationship between specially designed prenatal corticosteroid therapy and the molecular mechanisms underlying the prenatal programming of neurodevelopment in childhood and adulthood. Full article

Osteocalcin (OCN), a protein predominantly produced by osteoblasts in bone, has emerged as a significant factor in bone metabolism and reproductive function. This article reviews the latest research on the role of OCN beyond its traditional functions in bone mineralisation, particularly its influence on testicular steroidogenesis and male fertility. The structure and modifications of OCN are elaborated upon, highlighting its uncarboxylated form (ucOCN), which is becoming increasingly recognised for its bioactive properties. The impact of OCN on bone quantity, quality and strength is summarised, emphasising its role as a regulator of bone metabolism. Furthermore, the influence of ucOCN on testicular steroidogenesis and the involvement of GPRC6A, a G protein-coupled receptor, in mediating these effects are also explored. Evidence suggests that ucOCN regulates testosterone synthesis and spermatogenesis, which indirectly have the potential to influence bone metabolism integrity. In conclusion, OCN, particularly in its uncarboxylated form, plays a crucial role in bone metabolism and male fertility by regulating testicular steroidogenesis, with GPRC6A mediating these effects, thereby linking bone health and reproductive functions. Full article

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD). mTOR inhibitors, notably everolimus, have become central to TSC management, with documented efficacy in reducing the sizes of SEGAs and AMLs and showing promise in addressing additional TSC-related symptoms. Case Presentation: We report the case of an 11-year-old male diagnosed with TSC, presenting with hallmark features including hypopigmented macules, early-onset infantile spasms, SEGA, and AMLs. Initial interventions included adrenocorticotropic hormone (ACTH) therapy and sodium valproate for seizure management and a minimally invasive keyhole craniotomy for SEGA reduction. At age 12, oral everolimus therapy was introduced to address both SEGA recurrence risk and ASD-related social deficits. Over the course of 24 weeks, a reduction in the size and erythema of the patient’s FAs was observed, alongside improvements in social engagement, suggesting potential added benefits of systemic mTOR inhibition beyond tumor control. Results: Treatment with everolimus over a 24-month period led to significant reductions in both FA and AML size, as well as measurable improvements in ASD-associated behaviors. Therapeutic drug monitoring maintained serum levels within the effective range, minimizing adverse effects and underscoring the tolerability and feasibility of long-term everolimus administration. Conclusions: This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care. Full article

Background: Obstructive jaundice is a common health challenge in daily clinical practice caused by a heterogeneous group of benign and malignant conditions in or around extrahepatic bile ducts. This study aimed to investigate the causes of obstructive jaundice, analyze the age and sex distribution, and report the locations of obstruction. Methods: This was a retrospective study of electronic records of patients diagnosed with obstructive jaundice in the Hadhramout region in Yemen. Results: This study analyzed the data of 303 patients (mean age: 57 ± 17.99 years; range: 18–95 years); 60.40% (n = 183) were female, and 39.60% (n = 120) were male. The highest prevalence was found in middle-aged adults (n = 112, 36.96%), followed by the old (n = 101, 33.33%). Common bile duct (CBD) stones were the most common cause of obstructive jaundice (n = 175, 57.8%), followed by CBD stricture (n = 58, 19.1%), carcinoma of the head of the pancreas (n = 35, 11.6%), cholangiocarcinoma (n = 21, 6.9%), and external compression of the CBD (n = 2, 0.7%). CBD stones, cholangiocarcinoma, and ampulla of Vater masses were more prevalent in females (30.9%, 3.8%, and 2.2%, respectively) than in males (25.8%, 2.9%, and 1.7%, respectively). In contrast, CBD stricture and carcinoma of the pancreas were more frequent in males, occurring in 12.1% and 7.1% of male patients, respectively, compared to 7.9% and 4.9% in female patients. The primary obstruction site was the CBD (n = 254, 83.8%), followed by the head of the pancreas (n = 30, 9.9%), and the ampulla of Vater (n = 13, 4.3%). Conclusions: Obstructive jaundice predominantly affects middle-aged adults followed by the old-aged patients predominantly in females. The most common cause of obstructive jaundice was CBD stones, followed by CBD stricture, while carcinoma of the head of the pancreas was the most common malignant cause, followed by cholangiocarcinoma. Distal CBD is the most common anatomical location of obstructive jaundice. Full article

Background: Acetaminophen is generally considered safe when used according to the recommended guidelines. Consumption in excessive doses can lead to severe liver damage and, in critical cases, may even result in death. To reduce the effects of acetaminophen overdose, N-acetylcysteine (NAC) has been established as the preferred intervention to prevent liver damage. Objectives: The purpose of this updated systematic review and meta-analysis is to evaluate the potential benefits of a two-bag N-acetylcysteine (NAC) dosing regimen compared to the traditional three-bag protocol in the treatment of acetaminophen-induced liver toxicity. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The research team utilized the PubMed and Cochrane databases to perform a thorough and comprehensive search of the relevant literature from the inception of these databases up until January 2024. Results: Nine studies were included. The overall use of two-bag NAC was associated with lower anaphylactic reactions and gastrointestinal symptoms compared to the three-bag method. The rate of liver toxicity resolution was the same between the two treatment groups. Conclusions: The two-bag NAC regimen can be considered a safe and effective method for managing acetaminophen toxicity. Full article

Healthy working-age adults are susceptible to illness or caregiving requirements resulting from annual seasonal influenza, leading to considerable societal and economic impacts. The objective of this targeted narrative review is to understand the societal burden of influenza in terms of absenteeism and productivity loss, based on the current literature. This review includes 48 studies on the impact of influenza and influenza-like illness (ILI) and reports on the effect of influenza vaccination, age, disease severity, caring for others, comorbidities, and antiviral prophylaxis on absenteeism and productivity loss due to influenza/ILI, focusing on publications originating from Canada, Europe, and the United States. Influenza/ILI results in substantial work time and productivity loss among working adults and students in Canada, Europe, and the United States, particularly those who are unvaccinated, are <65 years of age, or who have severe disease. Considerable work time and productivity loss is attributable to illness and caregiver burden related to influenza. Further research is required on the impact of influenza on absenteeism and productivity loss in adults with comorbidities to support the development of effective employer policies for working adults with underlying health conditions. Full article

Obstructive sleep apnea syndrome (OSAS) is a frequently underdiagnosed sleep disorder marked by recurrent episodes of apnea and/or hypopnea during sleep, primarily resulting from the partial or complete collapse of the upper airway. OSAS significantly affects patients’ health and quality of life. Additionally, it is a recognized risk factor for inducing microsleep episodes during daily activities, particularly in occupations such as professional driving, where sustained attention is critical. The aim of our study was to identify an effective screening test for use in outpatient settings, capable of distinguishing patients with a severe form of OSAS. Patients who test positive with this screening tool would subsequently be prioritized for polysomnographic evaluation in a sleep laboratory. A total of 64 patients who underwent polysomnography (PSG) or polygraphy (PG) examination at our clinic were subsequently examined by USG of the tongue with measurements of tongue base thickness (TBT) and the distance between lingual arteries (DLA) during wakefulness and in a relaxed tongue position. The measurements of TBT and DLA were subsequently correlated with the apnea–hypopnea index (AHI) obtained from PSG or PG. In our cohort of patients diagnosed with severe OSAS, a TBT threshold of ≥65 mm served as an effective cutoff value. A TBT value of ≥65 mm reached an AUC value of 78.1%, sensitivity of 74.4%, specificity of 61.9%, positive predictive value of 80%, negative predictive value of 54.2% and overall accuracy of 70.3%. A DLA value of ≥30 mm in our sample of patients with severe OSAS showed an AUC of 76.5%, sensitivity of 69.8%, specificity of 71.1%, positive predictive value of 83.3%, negative predictive value of 53.6%, and overall accuracy of 70.3%. Tongue USG markers, particularly TBT and DLA measurements during wakefulness and in a relaxed tongue position, show potential as effective screening tools for identifying severe OSAS in European populations. These markers demonstrate improved accuracy over traditional screening questionnaires by reducing the likelihood of false-negative results. Patients with a positive screening should preferably be referred for polysomnography. In this way, patients with a serious illness could receive adequate therapy sooner. Full article

Background: Diabetes and hypertension are major global health challenges aggravated by COVID-19’s impact on healthcare and lifestyle factors. This study aims to compare the prevalence and associated socio-demographic factors of these conditions before and after the pandemic (2019 vs. 2022). Materials and Methods: We used data from Italy’s “Aspects of Daily Life” survey; 74,294 adults were included. Results: Results show a rise in diabetes prevalence from 7.76% in 2019 to 8.49% in 2022 (p < 0.05), while hypertension did not show this. Logistic regression analysis for the years 2019 and 2022 revealed a statistically significant association between the year 2022 and increased odds of diabetes (OR = 1.08, p = 0.008). BMI’s role as a risk factor intensified, with higher odds ratios (ORs) for both conditions in overweight and obese individuals in 2022. For example, obesity-related ORs for diabetes increased from 2.45 (95%CI 1.73–3.47) in 2019 to 3.02 (95%CI 2.09–4.35) in 2022, and for hypertension from 2.86 (95%CI 2.28–3.58) to 3.64 (95%CI 2.87–4.61). Lower education levels also showed a greater association with hypertension risk in 2022; subjects with only middle or high school diplomas had significantly higher ORs than individuals with higher education; there was a non-significant trend in 2019. However, diabetes risk associated with lower education remained stable and significant in both years. Conclusions: These findings suggest that the pandemic may have increased risk factors for diabetes and hypertension, particularly BMI and educational level, compared with the literature on the increased burden of chronic diseases during COVID-19. Full article

Background/Objectives: Myostatin, primarily produced by skeletal muscle, inhibits muscle growth and promotes protein degradation. It has been implicated in conditions such as obesity, insulin resistance, and cardiovascular disease. However, its association with endothelial function in chronic kidney disease (CKD) patients remains unclear. This study aimed to investigate the relationship between serum myostatin levels and endothelial function in 136 non-dialysis CKD patients at stages 3–5. Methods: Fasting blood samples were collected to measure serum myostatin levels using enzyme-linked immunosorbent assay kits. Endothelial function was evaluated non-invasively by measuring the vascular reactivity index (VRI) with a digital thermal monitoring test. Results: VRI values were classified as poor (<1.0, n = 25, 18.4%), intermediate (1.0 to <2.0, n = 63, 46.3%), or good (≥2.0, n = 48, 35.3%). Factors associated with poor vascular reactivity included older age (p = 0.026), elevated serum blood urea nitrogen (p = 0.020), serum creatinine (p = 0.021), urine protein-to-creatinine ratio (UPCR, p = 0.013), and myostatin levels (p = 0.003), along with reduced estimated glomerular filtration rate (p = 0.015). Multivariate regression analysis identified older age, higher serum creatinine, and log-transformed myostatin levels as significant independent predictors of lower VRI. Conclusions: These findings suggest that myostatin may serve as a potential biomarker for endothelial dysfunction in CKD patients. Future large-scale, longitudinal studies are warranted to confirm and extend our preliminary findings. Full article

The so-called trigeminal pontine sign has been described as a marker of different diseases, from multiple sclerosis to herpetic infections. First, it has been proposed as linear hyperintensity in the pons on the Magnetic Resonance Imaging (MRI) of patients with multiple sclerosis and trigeminal neuralgia. After these descriptions, it has been reported as incidental findings in the same patients and in patients with HSV or VZV infections. In addition, patients with neuromyelitis optica spectrum disorders (NMOSD) have been more rarely described with this neuroradiological sign. In this review, the main anatomical and neuroradiological issues underlying the trigeminal pontine sign are described, together with the limitations of the published studies from the clinical and neuroimaging point of view. Finally, the association with different diseases is detailed. Full article

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present in the emergency department (ED) with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. Acute liver failure is also a rare clinical presentation in the ED, being associated with high morbidity and mortality. It occurs most often in young patients without pre-existing liver disease, presenting unique challenges in clinical management. Most cases currently happen because of drug-induced liver injury (DILI), mainly from acetaminophen or idiosyncratic drug reactions. This case report aims to raise awareness among healthcare professionals regarding the two atypical presentations in ED and introduce a potential differential diagnosis when evaluating patients with fever and back pain or liver enzyme elevations with or without nonspecific symptoms associated with the development of jaundice. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced liver injury in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. At the first clinical examination in the ED, the patient presented pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever, vomiting, and jaundice. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, elevated liver enzymes, and hyperbilirubinemia with the predominance of indirect bilirubin. After analyzing the laboratory test results, we repeated and performed a more detailed anamnesis and medical history of the patient. Because of her increasing pain and persistent fever, she recognized excessive consumption in the last five days of drug-induced hepatotoxicity. We performed abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess collection fused to the interfibrillar level of the left iliopsoas muscle, a diagnosis we most likely would have missed. The patient was hospitalized in the General Surgery Department, and surgical abscess drainage was performed. The patient’s evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we hope that more cases of iliopsoas abscess will be accurately diagnosed. Moreover, no case report from the literature has presented IPA associated with DILI. This case is unique because our patient did not exhibit classic features of either pathology. This case also emphasizes the importance of a medical history that includes thorough evaluations of potential high utilization of drug-induced hepatotoxicity. Full article

Background: Calvarial defects in NF1 are rare and lack standardized management guidelines. This study seeks to shed light on calvarial defects in NF1 patients with extensive skull erosion. Methods: This case report focuses on clinical and radiological presentations and surgical interventions during six years of follow-up, comparing the results with those in the literature. Results: A five-year-old female with NF1 disease was diagnosed with a spontaneous calvarial defect in the occipital region and an arachnoid cyst underneath. The lesion enlarged progressively over the years and at the age of nine, she underwent her first surgery. Our surgery team performed a cranioplasty using a split-thickness bone graft harvested from the parietal bone after cyst decompression. Two years later, she underwent revision surgery with a titanium mesh plate due to total resorption of the initial bone graft and unsuccessful closure of the large defect. Conclusions: Calvaria defects are a relatively unknown aspect of NF1, and no standard treatment exists. Their management requires a personalized approach, considering factors like lesion size, and the potential for multiple interventions throughout the patient’s lifetime. Due to their progressive nature and the possibility of additional lesions, long-term follow-up is crucial for effective monitoring and intervention planning. Full article

Background: Oral squamous cell carcinoma (OSCC) causes considerable morbidity and mortality rates, posing a major global health burden. The management of the OSCC is multidisciplinary, but still the gold standard is surgical resection and reconstruction of the postablative defect. The appearance of secondary primary OSCC is not uncommon; however, it is quite rare that it appears on the skin of the flap that was used for reconstruction during the previous surgical therapy. Methods: We present three cases in which a secondary primary OSCC appeared on the skin of two radial forearm free flaps and two on regional pectoralis major flaps. Results: Our case series show that, although relatively rare, there is a chance of a secondary primary tumor on the flap used for intraoral reconstruction after the first oncological reconstruction. According to the latest and available literature, there is still no explanation of the underlying mechanism that leads to this occurrence. Conclusions: The learning point of this case series should be that, aside from the neck metastasis or recurrence of the primary oral cancer, the clinicians should also bear in mind that the flap itself should be physically examined in detail. Full article

Background/Objectives: The prevalence of bronchiectasis is increasing globally, and early detection using chest imaging has been encouraged to improve its prognosis. However, the sensitivity of a chest X-ray as a screening tool remains unclear. This study examined the chest X-ray features predictive of bronchiectasis. Methods: We retrospectively reviewed the chest X-rays of patients with bronchiectasis diagnosed using high-resolution computed tomography who visited our institute from January 2013 to March 2020. Patients with cardiac pacemakers, lung cancer, and interstitial pneumonia, which might bias the detection of bronchiectasis, were excluded. Two respiratory physicians independently determined the presence or absence of potential features reflecting bronchiectasis, including a vague cardiac silhouette on chest X-rays. Results: The study enrolled 130 patients, including 72 women (55.4%), with a mean age of 72 years. The features observed on chest X-rays included granular shadows (88.5%, n = 115), vague cardiac silhouettes (48.5%, n = 64), nodular shadows (45.4%, n = 59), a tram-track appearance (35.4%, n = 46), pleural thickening (26.9%, n = 35), vague diaphragm silhouettes (25.4%, n = 33), and a ring sign (24.6%, n = 32). The kappa values for these features were 0.271, 0.344, 0.646, 0.256, 0.312, 0.514, and 0.376, respectively. Conclusions: Although traditional chest X-ray features believed to reflect bronchiectasis, such as the tram-track appearance or ring sign, were not frequently seen, vague cardiac silhouettes and granular shadows had high positivity rates, indicating their potential utility for bronchiectasis screening. However, the interobserver concordance rates were unsatisfactory. Full article

Objectives: Cyclosporine A promotes gingival fibrosis by enhancing the proliferation of gingival fibroblasts, leading to gingival overgrowth. The population of gingival fibroblasts is regulated by cell cycle machinery, which balances cell growth and inhibition. Cells that detect DNA damage pause at the G1/S checkpoint to repair the damage instead of progressing to the S phase. Previous studies have linked drug-induced gingival overgrowth to the response of fibroblasts to lipopolysaccharide (LPS) and cyclosporine A. This research investigates the effects of cyclosporine A on the G1/S checkpoint and its mediators in LPS-treated gingival fibroblasts to clarify the mechanisms behind cyclosporine-A-induced gingival overgrowth. Methods: Semi-confluent human gingival fibroblasts were treated with LPS or cyclosporine A in DMEM. Cell proliferation was evaluated by counting the total number of cells. The distribution of the cell cycle phases was analyzed using flow cytometry. Additionally, the expression levels of mRNAs and proteins related to cell cycle regulators were quantified by reverse-transcription quantitative PCR and Western blotting, respectively. Results: Cyclosporine A treatment significantly enhanced cell proliferation and the G1-S cell cycle transition. It increased the mRNA levels of CDC25A and CYCLIN D while decreasing those of RB1, SMAD3, and SMAD4. Additionally, it upregulated the protein levels of CDC25A, CYCLIN D, CDK4, CDK6, and pRB and downregulated the protein levels of SMAD3 and SMAD4. Conclusions: Gingival overgrowth induced by cyclosporine A could be attributed to these alterations. Full article

Introduction. Recently published data suggested significantly lower pacing-induced cardiomyopathy (PICM) incidence with conduction system pacing (CSP). Because most data evaluated only the impact on the left ventricle, this study aimed to assess changes in echocardiographic parameters of morphology and function for all heart chambers in patients with baseline preserved and mid-range LVEF over a medium-term follow-up period after CSP. Methods. A total of 128 consecutive patients with LVEF > 40% and successful CSP for bradyarrhythmic indication were prospectively enrolled. A complete 2D echocardiographic examination was performed at baseline and the last follow-up. Results. In total, 38 patients received His bundle pacing (HBP) and 90 received left bundle branch area pacing (LBBAP). The mean follow-up period was 699.2 ± 177.2 days, with 23 patients lost during this period. The ventricular pacing burden for the entire group was 97.2 ± 4.2%. Only three patients (2.9%) met the criteria for PICM. CSP led to a significant increase in LVEF (from 54.2 ± 7.9 to 56.7 ± 7.8%, p = 0.01) and a significant decrease in LV diastolic (from 107.2 ± 41.8 to 91.3 ± 41.8 mL, p < 0.001) and systolic (from 49.7 ± 21.4 to 39.5 ± 18.2 mL, p < 0.001) volumes. There were no significant changes in E/e′, mitral regurgitation, atrial volumes, and right ventricle (RV) diameter. There was a significant improvement in RV function. Tricuspid regurgitation was the only parameter that worsened. There were no differences in evolution for each echocardiographic parameter between the HBP and the LBBAP groups. Conclusions. HBP and LBBAP are equally protective for harmful changes in both atria and ventricles. The prevalence of PICM, defined as a decrease in LVEF, is very low with CSP. Full article

Background/Objectives: Ischemic heart disease (IHD) significantly affects mental health, with gender-specific differences being observed in psychological responses. This pilot study aimed to explore these differences in the demographic, clinical, psychological, psychiatric, and social profile of patients diagnosed with IHD. Methods: A descriptive, cross-sectional design was used, recruiting 183 adult patients diagnosed with coronary artery disease and depression at the Psychiatry Department of Arad County Emergency Hospital, Romania, between May 2021 and May 2024. Data were collected using a self-developed tool, named the Depression Assessment in Ischemic Heart Disease Questionnaire (DA-IHDQ), alongside standardized assessments. Statistical analysis was performed using JASP statistical software (Version 0.19.1, University of Amsterdam, Amsterdam, Netherlands), employing binomial and multinomial tests for categorical data, and Cronbach’s alpha was used to assess internal consistency. Results: This study found significant demographic differences, with female patients exhibiting higher levels of emotional distress and severe depression compared with the male subjects. Women reported greater social isolation and a stronger desire to seek for psychological or psychiatric support. Furthermore, a positive correlation between depression severity and physical symptoms was observed in both genders. Conclusions: These findings highlight the importance of recognizing gender-specific responses to IHD, emphasizing the need for tailored interventions in mental healthcare and cardiac rehabilitation. Future research should further explore these differences to enhance the understanding of the psychosocial/psychiatric aspects of IHD and improve patient outcomes. Full article

Background and objectives: The correlation between diminished 25-hydroxyvitamin D (25-(OH)D) concentrations and heightened disease activity in systemic lupus erythematosus (SLE) patients remains contentious, as clinical studies have yielded conflicting outcomes—some propose a potential link, while others assert no relationship exists. Nonetheless, all studies report a significant prevalence of low 25-(OH)D levels among SLE patients. This study aimed to assess the frequency of low serum levels of 25-(OH)D in Mexican patients with SLE and to evaluate the correlation between 25-(OH)D deficiency or insufficiency and disease activity levels. Materials and Methods: This retrospective analysis comprised patients admitted to our hospital from November 2022 to October 2023, diagnosed with SLE, and had their serum 25-(OH)D levels tested upon admission. The frequency of low levels of 25-(OH)D was assessed, and clinical and demographic data were gathered to examine potential causes linked to 25-(OH)D deficiency or insufficiency. Results: A total of 61 patients were included, and 87% (n = 53) had low serum 25-(OH)D levels. Patients with 25-(OH)D deficiency (n = 21) were significantly younger (mean 23 vs. 39 years, p = 0.04) and had higher protein levels in 24 h urine protein (1.8 vs. 1.1 g/24 h, p = 0.006) than patients who presented only 25-(OH)D insufficiency, without significant differences in other indicators of disease activity. Conclusions: In this investigation, patients with SLE exhibited a high frequency of low serum levels of 25-(OH)D, consistent with existing literature; however, no significant correlations were identified between 25-(OH)D levels and indicators of disease activity. These findings require validation in subsequent research. Full article

Background: Identifying physical activity (PA) and its barriers among middle-aged women may aid in the development of age-specific health promotion interventions. In Egypt, women, particularly those in the workforce, typically face numerous barriers that result in low levels of PA. This research seeks to assess the prevalence of health-enhancing physical activity (HEPA) among working women at Mansoura University and identify the associated barriers. Methods: This cross-sectional study employs a quantitative methodology that includes an analytic component. We studied a non-random sample of 760 Egyptian women employed at Mansoura University. Sociodemographic data were collected, and the international physical activity questionnaire (IPAQ) short form was used to assess the level of PA. Additionally, the Barriers to Being Active Quiz (BBAQ) was used to assess barriers to PA. Results: One-fourth of women engage in HEPA; 44.9% are classified as minimally active, while 30.1% are inactive. Multivariable logistic regression analysis showed the type of job is an independent predictor of HEPA, with ARR of 1.7 for manager and administrative roles. The total BBAQ score significantly predicts HEPA (ARR = 0.94). Social influences and lack of willpower scores are significant independent predictors of HEPA (ARR = 0.9 and 0.8, respectively). Most individuals encounter two to five barriers, with only 11.3% experiencing no PA barriers. The most frequently reported barrier is the lack of energy (80.4%), followed by the lack of resources, willpower, and time (74.04%, 69.6%, and 69.4%, respectively). Conclusions: The prevalence of HEPA is low among working women at Mansoura University. Policymakers can utilize findings to promote engagement with and adherence to physical activity. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD. Full article

Noncardiogenic pulmonary edema after cardiac surgery is a rare but severe complication. The etiology remains poorly understood; however, the issue may arise from multiple sources. Possible causes include a significant inflammatory response or an autoimmune process. Pulmonary edema resulting from noncardiac etiologies can necessitate extracorporeal membrane oxygenation (ECMO) because most of the cases present a substantial volume of fluid expelled from the lungs and the medical team must manage the inability to achieve effective ventilation. A 64-year-old patient with known heart disease was admitted to our clinic with acute pulmonary edema. His medical history included Barlow’s disease, severe mitral regurgitation (IIP2), moderate–severe tricuspid regurgitation, and moderate pulmonary hypertension. The patient had a coronary angiography performed in a prior hospitalization before the surgical intervention which indicated the absence of coronary lesions. Preoperative screening (nasal, pharyngeal exudate, inguinal pouch culture, and urine culture) was negative, with no active dental infections. The patient was stabilized, and 14 days post-admission, mitral and tricuspid valve repair was performed via a thoracoscopic approach. After being admitted to intensive care post-surgery, the patient quickly developed pulmonary edema, producing a large volume (4.5 L) of yellow secretions through the intubation tube followed by hemodynamic instability necessitating high doses of medications to support circulation but no cardiorespiratory arrest. Due to his worsening condition, the patient was urgently taken back to the operating room, where veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to support oxygenation and stabilize the patient. Full article

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade, which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. A comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-induced celiac disease. Regarding pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to a rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and the discontinuation of antineoplastic immunotherapy. Full article

Background: Chronic pain is defined as any persistent or recurring pain lasting longer than 3 months that significantly affects a person’s quality of life. Millions worldwide are impacted by chronic pain, but its subjective nature makes it difficult to quantify and compare between individuals. Methods: This retrospective analysis aimed to examine the differences in pain perception and reporting between male and female patients, as well as how their pain was managed. Data from 1995 patients who met the inclusion criteria were selected from the Advocate Illinois Masonic Pain Clinic database. The types of pain assessed in this study included lower back pain, neck pain, and osteoarthritis. Results: The findings indicate that females suffer more from chronic pain conditions than males, where lower back pain had the highest prevalence in both sexes (63.7% reported). Baseline Numeric Rating Scale (NRS) scores at the first inpatient visit were statistically higher in females than males (7.95 ± 1.35 vs. 7.72 ± 1.46, p = 0.006). After 1 year of treatment, both sexes reported a clinical improvement in their symptoms. With regards to medication, females reported a higher use of medications such as muscle relaxants, benzodiazepines, and tricyclic antidepressants, while males reported a higher use of opioids (measured in MMEs). Conclusions: This study reveals a significant sex difference in the reporting of non-cancer-related chronic pain, with females reporting higher pain intensity than males. Full article

Background/Objectives: Despite advancements in antiretroviral therapy (ART), HIV-positive individuals face heightened risks of cardiovascular and gastrointestinal (GI) complications, often linked to persistent systemic inflammation. Left ventricular diastolic dysfunction (LVDD), prevalent in HIV patients, exacerbates this inflammatory state and may contribute to worsened GI symptoms. This study aims to explore the association between LVDD, systemic inflammation, and gastrointestinal symptoms in HIV-positive patients undergoing ART. The primary objective is to analyze how LVDD contributes to the inflammatory burden and its impact on gastrointestinal health in this population. Methods: This cross-sectional study included 320 participants divided into three groups: HIV-positive with LVDD (n = 80), HIV-positive without LVDD (n = 120), and HIV-negative controls (n = 120). Levels of inflammatory biomarkers—CRP, IL-6, TNF-α, fibrinogen, IL-1β, IFN-γ, and D-dimer—were measured, and GI symptoms were assessed. Echocardiographic evaluations were performed to determine LVDD presence and severity, while multivariate logistic regression identified predictors of GI complications. Results: Patients in the HIV + LVDD group exhibited significantly elevated levels of TNF-α, CRP, and D-dimer compared to other groups, correlating with higher incidences of nausea, diarrhea, and abdominal pain. TNF-α emerged as the strongest predictor of GI symptoms, underscoring its role in the pathophysiology linking cardiovascular and GI distress in this population. Persistent inflammation and coagulation abnormalities in the ART + LVDD group suggest that ART alone may not fully mitigate these complications. Conclusions: Our findings emphasize the compounded inflammatory burden in HIV patients with LVDD, highlighting the need for integrated approaches that address both cardiovascular and GI symptoms. Anti-inflammatory therapies targeting specific biomarkers like TNF-α could improve clinical outcomes, supporting a more comprehensive strategy to managing HIV-related comorbidities beyond viral suppression. Full article

Introduction: Consuming hypercaloric diets during pregnancy induces metabolic, immune, and maternal intestinal dysbiosis disorders. These conditions are transferred to the offspring through the placenta and breastfeeding, increasing susceptibility to metabolic diseases. We investigated the effect of L. rhamnosus GG supplementation on offspring maternally programmed with a hypercaloric diet. Methods: Our study involved sixteen female Wistar rats aged ten weeks, which were divided into four groups based on their diets: control (Ctrl), cafeteria (CAF), control + probiotic (PRO), and cafeteria + probiotic (CPRO). The control + probiotic and cafeteria + probiotic groups received a daily oral administration of 250 μL of L. rhamnosus GG cell suspension (equivalent to 10⁹ UFC) for nine weeks. The body weight of the animals was recorded weekly, and their food intake was monitored every 24 h. An oral glucose tolerance test was conducted on the offspring at seven weeks of age. At the ninth week of age, animals were euthanized, and blood, tissues, and organs were collected. Results: Maternal supplementation with L. rhamnosus GG decreased food intake and the average birth weight, improved glucose sensitivity, and lowered the levels of LDL, cholesterol, triglycerides, and mesenteric adipose tissue in offspring compared with the control and cafeteria groups. Conclusions: Our findings indicate that supplementing with LGG during maternal programming could protect offspring from metabolic disruptions caused by a hypercaloric maternal diet. Full article

Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the gastric epithelium and is associated with a range of gastrointestinal disorders, exhibiting a global prevalence of approximately 50%. Despite the availability of treatment options, H. pylori frequently reemerges and demonstrates increasing antibiotic resistance, which diminishes the efficacy of conventional therapies. Consequently, it is imperative to explore non-antibiotic treatment alternatives to mitigate the inappropriate use of antibiotics. This review examines H. pylori infection, encompassing transmission pathways, treatment modalities, antibiotic resistance, and eradication strategies. Additionally, it discusses alternative therapeutic approaches such as probiotics, anti-biofilm agents, phytotherapy, phototherapy, phage therapy, lactoferrin therapy, and vaccine development. These strategies aim to reduce antimicrobial resistance and enhance treatment outcomes for H. pylori infections. While alternative therapies can maintain low bacterial levels, they do not achieve complete eradication of H. pylori. These therapies are designed to bolster the immune response, minimize side effects, and provide gastroprotective benefits, rendering them suitable for adjunctive use alongside conventional treatments. Probiotics may serve as adjunctive therapy for H. pylori; however, their effectiveness as a monotherapy is limited. Photodynamic and phage therapies exhibit potential in targeting H. pylori infections, including those caused by drug-resistant strains, without the use of antibiotics. The development of a reliable vaccine is also critical for the eradication of H. pylori. This review identifies candidate antigens such as VacA, CagA, and HspA, along with various vaccine formulations, including vector-based and subunit vaccines. Some vaccines have demonstrated efficacy in clinical trials, while others have shown robust immune protection in preclinical studies. Nevertheless, each of the aforementioned alternative therapies requires thorough preclinical and clinical evaluation to ascertain their efficacy, side effects, cost-effectiveness, and patient compliance. Full article

People of all ages can contract pneumonia, and it can cause mild to severe disease and even death. In addition to being a major cause of death for elderly people and those with prior medical conditions such as diabetes, it isthe world’s biggest infectious cause of death for children. Diabetes mellitus is a metabolic condition with a high glucose level and is a leading cause of lower limb amputation, heart attacks, strokes, blindness, and renal failure. Hyperglycemia is known to impair neutrophil activity, damage antioxidant status, and weaken the humoral immune system. Therefore, diabetic patients are more susceptible to pneumonia than people without diabetes and linked fatalities. The absence of quick, precise, simple, and affordable ways to identify the etiologic agents of community-acquired pneumonia has made diagnostic studies’ usefulness contentious. Improvements in biological markers and molecular testing techniques have significantly increased the ability to diagnose pneumonia and other related respiratory infections. Identifying the risk factors for developing severe pneumonia and early testing in diabetic patients might lead to a significant decrease in the mortality of diabetic patients with pneumonia. In this regard, various risk factors, traditional testing techniques, and pathomechanisms are discussed in this review. Further, biomarkers and next-generation sequencing are briefly summarized. Finding biomarkers with the ability to distinguish between bacterial and viral pneumonia could be crucial because identifying the precise pathogen would stop the unnecessary use of antibiotics and effectively save the patient’s life. Full article