Medicine and Pharmacology

Abstract: Background: Maxillary sinus fungus ball (MSFB) is a non-invasive form of fungal rhinosinusitis characterized by an accumulation of fungal material within the sinus lumen without tissue invasion. Clinical manifestations are often non-specific, whereas computed tomography (CT) may provide important diagnostic clues. Methods: We describe five patients with clinical and radiological findings suggestive of MSFB who underwent endoscopic sinus surgery. Clinical manifestations, nasal endoscopic findings, CT features, histopathological and/or mycological results, and surgical management were reviewed. Results: The patients ranged from 29 to 66 years of age. All lesions were unilateral and involved the maxillary sinus. Purulent nasal discharge and headache were the predominant symptoms. CT demonstrated maxillary sinus opacification or mucosal thickening associated with intralesional calcifications in all patients. All patients underwent endoscopic maxillary sinus surgery. Fungal culture was negative in three patients and positive for filamentous fungi in one patient; histopathological examination in the remaining patient showed inflammatory tissue. Conclusions: MSFB should be considered in persistent unilateral maxillary sinus disease, particularly when CT demonstrates intralesional hyperattenuation or calcification. Negative fungal culture does not exclude MSFB. Diagnosis should integrate clinical, endoscopic, radiological, intraoperative, histopathological, and mycological findings. Endoscopic sinus surgery remains the treatment of choice for symptomatic disease.

Abstract: Suspected immune thrombotic thrombocytopenic purpura (iTTP) creates a dual emergency: treatment must begin before ADAMTS13 confirmation, while lethal mimics must be investigated concurrently. A 44-year-old woman presented with fever, severe thrombocytopenia, progressive limb weakness, and multifocal cerebral infarctions. Although the schistocyte proportion was <1% and her PLASMIC score was 5, iTTP could not be safely excluded. ADAMTS13 activity was sampled before treatment, and plasma exchange plus corticosteroids was started. Blood cultures grew methicillin-susceptible Staphylococcus aureus. Despite three negative transthoracic echocardiograms, transesophageal echocardiography demonstrated a 10-mm mitral vegetation, establishing infective endocarditis (IE). Pretreatment ADAMTS13 activity was 35%, allowing TTP-directed therapy to be withdrawn. IE can produce thrombocytopenia, microangiopathic hemolysis, TMA-like presentations, and occasionally marked ADAMTS13 reduction; conversely, schistocytes may be initially inapparent in true iTTP. Thus, neither a low schistocyte count nor an intermediate prediction score should end diagnostic reasoning. When iTTP and IE remain plausible, pretreatment ADAMTS13 sampling, risk-adapted empiric TTP therapy, blood cultures, antimicrobial treatment, and definitive cardiac imaging should proceed in parallel.

Abstract: Objectives: Sjögren’s disease (SjD) and Hashimoto’s thyroiditis (HT) are closely associated autoimmune diseases. This study compared elastographic changes in the major salivary and thyroid glands of patients with SjD and HT. Methods: This cross-sectional study included 30 SjD and 31 HT patients. Ultrasonography and Shear Wave Elastography (SWE) were performed to evaluate the parotid, submandibular, and thyroid glands. Salivary gland structural changes were assessed using OMERACT scores, while thyroids were evaluated for heterogeneity and pseudonodular appearance. Results: Thyroid parenchymal heterogeneity was more frequent in HT patients, though 43% of SjD patients also exhibited HT-like thyroid features. In contrast, no HT patients showed SjD-like salivary gland changes (OMERACT score ≥3). Elastographic measurements of thyroid and salivary glands did not differ significantly between groups, even after age adjustment via ANCOVA. Furthermore, clinical disease activity (ESSDAI) did not correlate with elastographic findings in SjD. However, SjD patients with severe structural changes (OMERACT score ≥4) had significantly higher elastography indices exclusively in the left parotid gland (p=0.004). Conclusion: SjD is associated with thyroiditis-like changes in the thyroid, but HT lacks structural salivary gland involvement. Elastographic findings of these glands are similar in both diseases. Generally, ultrasonographically detected salivary gland parenchymal changes in SjD do not significantly affect glandular elasticity.

Abstract: Background and Objectives: Metabolic perturbations frequently occur during the acute phase of critical illness and may disrupt lipid homeostasis. Acute respiratory distress syndrome (ARDS) is a severe condition that contributes to multiple organ failure and is associated with high morbidity and mortality in critically ill patients with sepsis. This study aimed to evaluate the association between conventional plasma lipid parameters and clinical outcomes in critically ill sepsis patients. Materials and Methods: We conducted a prospective observational cohort study of critically ill sepsis patients in Taiwan between October 2020 and July 2025. Conventional plasma lipid parameters and clinical variables were measured at intensive care unit (ICU) admission. Clinical outcomes were compared between patients stratified by plasma HDL-C levels. Results: A total of 285 critically ill patients with sepsis were included. The overall all-cause hospital mortality rate was 37.9%. Patients with ARDS had significantly higher C-reactive protein (CRP) and interleukin-6 (IL-6) levels, higher risk of organ failure (i.e., APACHE II and SOFA scores), and lower plasma HDL-C levels (all p < 0.05). Non-survivors exhibited significantly greater organ failure severity and lower HDL-C levels compared with survivors (all p < 0.05). Patients with low HDL-C (≤ 22.5 mg/dL; n = 162, 56.8%) had significantly higher CRP and IL-6, greater organ failure severity, and increased 28-, 60-, 90-day, and hospital mortality, compared with those with high HDL-C (> 22.5 mg/dL; n = 123, 43.2%) (all p < 0.05). In multivariable logistic regression analyses, lower HDL-C were independently associated with hospital mortality. Conclusions: Plasma HDL-C levels at ICU admission are independently associated with hospital mortality in critically ill patients with sepsis. HDL-C may serve as a simple, accessible, and useful for early risk stratification in critically ill patients with sepsis.

Abstract: Background/Objectives: Metabolic syndrome (MetS) is a common cardiometabolic condition characterized by clustering of metabolic risk factors. Early identification in routine clinical practice remains challenging. This study aimed to explore the performance of artificial intelligence (AI)–based models for the prediction of MetS using routinely available clinical and laboratory parameters, with a particular focus on serum uric acid. Methods: This retrospective study was conducted using a publicly available dataset including 640 individuals (320 MetS-positive and 320 MetS-negative). MetS was defined according to modified National Cholesterol Education Program Adult Treatment Panel III criteria. Machine learning models were developed using combinations of age, sex, body mass index, uric acid, and albumin. Logistic regression, support vector machines, decision trees, k-nearest neighbors, and random forest algorithms were evaluated. Model performance was assessed using accuracy, area under the receiver operating characteristic curve (AUC), precision, recall, and F1-score. Internal validation was performed using 5-fold cross-validation. Results: Individuals with MetS had significantly higher uric acid levels compared to those without MetS (6.02 ± 1.57 vs. 2.84 ± 0.35 mg/dL, p < 0.001), while albumin levels were similar. The evaluated models demonstrated high classification performance within the study dataset, with accuracy values up to 0.99 and AUC values up to 0.99. Models using a limited number of variables, particularly body mass index, age, and uric acid, showed consistent performance. Models based on uric acid and albumin achieved accuracy values around 0.98, while single-variable models using uric acid alone achieved accuracy of 0.97. Conclusions: AI-based models using a limited set of routinely available clinical and laboratory parameters demonstrated the potential to classify MetS. Serum uric acid consistently emerged as one of the most discriminative variables, supporting its potential role as a clinically informative and accessible biomarker in MetS classification.

Abstract: Orofacial myofunctional therapy (OMT) addresses functional impairments involving tongue and lip function, swallowing, and breathing behaviors. Mobile health (mHealth) platforms may facilitate structured delivery and monitoring of home-based exercises, but evidence regarding feasibility in clinical practice remains limited. This study evaluated the feasibility of a smartphone-based OMT platform by examining pre- to post-intervention changes in functional measures and adherence. A retrospective observational analysis was conducted using 15 de-identified clinical records from a single clinical database. Eligible records included documented platform use, baseline and post-intervention measurements, symptoms of at least six months’ duration, and participation in the 16-week intervention. Measures included lip pressure, tongue pressure, swallowing performance, peak nasal inspiratory flow (PNIF), forward head posture, and incentive spirometry. Paired t-tests or Wilcoxon signed-rank tests were used as appropriate. Significant pre- to post-intervention changes were observed in forward head posture, PNIF, incentive spirometry, lip pressure, tongue pressure, and swallowing performance. Adherence was high, with 14 of 15 participants (93%) completing the 16-week program. No adverse events were reported. This retrospective analysis provides preliminary feasibility data for smartphone-delivered OMT. Findings are exploratory and do not establish efficacy, causality, diagnostic validity, or effectiveness for specific medical conditions. Prospective controlled studies using standardized outcome measures are warranted.

Abstract: Background. Modulation of the gut-liver axis with non-viable microbial components is a promising approach to correct metabolic disorders. The aim of the study was to evaluate the short-term efficacy and safety of the postbiotic lysate Lactobacillus rhamnosus DV-NRRL B-68023 on non-invasive measures of hepatic steatosis, trans-aminase activity, and anthropometric parameters in patients with MASLD. Methods. In a randomized, double-blind, placebo-controlled trial (NCT06352697), 52 patients were assigned 1:1 to receive the postbiotic Del-Immune V® Extra (100 mg twice daily; n=26) or placebo (n=26) for 3 months followed by a 3-month follow-up without treatment. The primary endpoints were FLI, HSI, and TyG. Additionally, lipid profile, ALT, AST and GGT activities, inflammatory markers and body composition indices were assessed. Results. In the ITT analysis, FLI decreased significantly more in the postbiotic group compared to placebo (p=0.049). HSI decreased in both groups without a significant difference between them (p=0.737), and a downward trend was observed for TyG. In the PP analysis (n=24 in each group), postbiotics were associated with a significant de-crease in waist circumference (p=0.003) and a trend towards a decrease in visceral fat (p=0.079). ALT activity decreased by 17.5% (p=0.011), AST by 10.4% (p=0.007), but gradually returned to baseline values after treatment discontinuation. Lipid profile and inflammation indices did not change significantly. All adverse events were mild and self-limiting. Conclusions. Three months of postbiotic L. rhamnosus lysate DV-NRRL B-68023 ad-ministration was well tolerated and improved noninvasive measures of steatosis and abdominal obesity in patients with MASLD. The effect on transaminases was transient. Postbiotics may be considered as an additional noninvasive approach to the treatment of MASLD in combination with lifestyle changes.

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder shaped by inter-organ crosstalk: dynamic, bidirectional communication through which the liver and endocrine organs, gut, adipose tissue, brain, kidney, skeletal muscle, and bone exchange signals to coordinate metabolism, immunity, and tissue homeostasis. Across these axes, neural circuits, hormones, cytokines, adipokines, hepatokines, myokines, osteokines, bile acids, microbial metabolites, lipids, extracellular vesicles, and microRNAs integrate nutrient handling, insulin action, immunity, mitochondrial function, and tissue remodeling. Perturbation of these networks converts physiological homeostasis into self-reinforcing loops of substrate overflow, endocrine dysregulation, dysbiosis, inflammation, and fibrogenesis, while hepatic dysfunction propagates renal, neurocognitive, cardiometabolic, and musculoskeletal complications. This framework helps explain why individuals with comparable steatosis show divergent trajectories of metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, extrahepatic disease, and treatment response. It also highlights tractable points of intervention, including restoration of adipose buffering, modulation of gut microbial and bile-acid signaling, correction of endocrine drivers, preservation of muscle and bone, and integrated cardio–kidney–liver risk reduction across different disease stages and clinical phenotypes. We argue that precision hepatology should move beyond isolated assessment of liver fat and fibrosis towards multidimensional phenotyping of dominant crosstalk mechanisms. Longitudinal multi-omic studies and trials incorporating outcomes across organs are now required to distinguish causal signals from disease correlates, define clinically actionable endotypes, and test whether targeting one node can restore durable metabolic and functional resilience throughout the interconnected MASLD network, while improving patient-centered outcomes across the disease course.

Abstract: Background/Objectives: Diabetic foot syndrome (DFS) is a serious complication of diabetes that poses a high risk of morbidity/mortality. The management of these patients requires a multidisciplinary team approach, as these patients are “complex” and “fragile”. Despite this, the rate of re-amputation remains high. This study aims to evaluate the degree of multidimensional complexity in patients with DFS using specific tools and to determine if it is an additional risk factor for amputation. Methods: The study was conducted on a cohort of 115 patients referred to a Tertiary Center of University Hospital of Modena from January to December 2021. The study used 12 variables to assess patients, including age, sex, caregiver presence, BARTHEL INDEX, LAWTON-BRODY SCALE, Mini Mental State Examination, Cumulative Illness Rating Scale (CIRS), SINBAD system, Malnutrition Universal Screening Tool and Italian National Association of Social Workers Tool. All patients were taken care of by the Multidisciplinary Team in order to standardize care according to the updated guidelines. Patients were classified based on amputation and revascularization status. Statistical analyses were performed using R software version 4.1.1. Results: The analysis showed that a greater clinical complexity and more severe ulcer had a greater risk of amputation (respectively OR 3.13, p 0.035 and OR 1.53, p 0.015). The study confirms the predictive value of tools such as CIRS and SINBAD in amputation risk stratification for patients with DFS. Conclusions: Although limitations, due to a small sample size, the use of multidisciplinary approach and multidimensional evaluation tools can identify “unconventional” risk factors that, if modified, could delay and/or reduce the risk of amputation. Further studies are needed to investigate the role of caregiving in the prevention of amputation in patients with DFS.

Abstract: Many people take more than one medicine at a time — a spoon of cough syrup, a fever tablet, a cold-and-flu sachet — often on the same afternoon, and sometimes with a drink of alcohol. This is casually called a “medicine cocktail.” This article explains, in plain school-textbook language, why such combinations can be harmful. It corrects a common misunderstanding: dangerous combinations usually do not arise because two drugs meet in a glass and brew a brand-new poison. Far more often the harm comes from duplicated active ingredients, additive effects, or the way the body chemically transforms a drug once it is swallowed. We examine what makes any molecule “poisonous,” the small number of cases where a genuinely toxic new molecule is formed, and — in an expanded central section — why alcohol is the single most dangerous thing to mix with everyday medicines. Every worked example ends with a short, simple “what to avoid” box written for school students. All chemical changes are given as balanced equations.

Abstract: Increasingly sophisticated genetic panels have disproportionately increased the identification rate of novel gene variants in Mendelian conditions. In Fabry disease (FD), this phenomenon is particularly relevant because the pathogenicity of individual gene variants has an impact on treatment proposal. In fact, FD is characterized by a phenotypical heterogeneity depending on patients' biological sex and the underlying GLA mutation. This represents the main reason why integrating genetic data with phenotypic expression is challenging, and defining the pathogenic role of novel variants remains complex. The early discrimination between pathogenic and non-pathogenic GLA variants is crucial to enable timely initiation of treatments such as Enzyme Replacement Therapy (ERT), which has been shown to significantly slow down the progression of the disease. In fact, the most severe cases of FD have a significantly compromised quality of life up to reduced life expectancy, especially with regard to cardiac and renal complications. In recent years, some GLA variants have been reclassified following investigation and clinical observations by multidisciplinary working groups that have made it possible to better define if they are pathogenic or not. Regardless of the clinical scenario leading to the identification of a novel GLA variant (i.e., family screening, neonatal screening, clinical profile suggestive of FD, incidental finding), any genetic finding becomes relevant when it is complemented by laboratory, clinical and instrumental investigations that require a concerted effort among the many health care professionals involved in the diagnostic process. The present work summarizes the outcomes of a series of expert meetings with the aim to provide some shared and practical indications for managing the genetic report of a novel GLA variant so to promptly start the most suitable diagnostic journey and assess corresponding phenotype and clinical characterization.

Abstract: Background: Acute myeloid leukemia (AML) remains a treatment challenge due to the systemic toxicity of conventional chemotherapy. Venetoclax, a selective BCL-2 inhibitor, shows promise in the treatment of AML; however, its clinical efficacy is limited due to inadequate pharmacokinetic properties. PEG-PLGA-based polymeric nanoparticles provide a biocompatible platform for improving drug stability, controlling release behavior, and potentially enhancing intracellular drug availability. Methods: The physicochemical properties of VEN-PEG-PLGA nanoparticles were evaluated by dynamic light scattering (DLS), scanning electron microscopy (SEM), drug loading analysis, and in vitro drug release. Antileukemic activity was assessed in THP-1 cells using the CCK-8 cytotoxicity assay, propidium iodide (PI)-based cell cycle analysis, Annexin V-FITC/PI apoptosis assay, and Western blot analysis of Bcl-2, cleaved caspase-3, cleaved caspase-9, ERK1/2, phospho-ERK1/2 (p-ERK1/2), NF-κB, and phospho-NF-κB (p-NF-κB). Results: VEN-PEG-PLGA nanoparticles exhibited a mean particle size of 186 ± 4 nm with a polydispersity index of 0.195 ± 0.005, 89% loading efficiency, and 6.26% loading capacity. The nanoparticles demonstrated a pH-responsive drug release profile, reaching approximately 72–74% cumulative release at pH 7.4 and 88–89% at pH 5.5 after 96 h. In THP-1 cells, both free venetoclax and VEN-PEG-PLGA na-noparticles exhibited concentration-dependent cytotoxicity, although free venetoclax showed greater cytotoxicity, with EC₅₀ values of 5.59 × 10⁻⁷ M and 1.35 × 10⁻⁶ M, respectively. Cell cycle analysis demonstrated an increase in the G0/G1 cell population from 49.30% in the control group to 61.04% following treatment with VEN-PEG-PLGA nanoparticles, accompanied by a reduction in the G2/M phase. Annexin V-FITC/PI analysis showed that VEN-PEG-PLGA nanoparticles in-creased the proportion of late apoptotic cells to 36.99%, compared with 22.13% following free venetoclax treatment. Western blot analysis demonstrated reduced Bcl-2, ERK1/2, phos-pho-ERK1/2, and phospho-NF-κB expression, together with increased cleaved caspase-3 and cleaved caspase-9 expression in both treatment groups, with these changes being more pronounced in the VEN-PEG-PLGA nanoparticle-treated group. Conclusions: Venetoclax-loaded PEG-PLGA nanoparticles modulated apoptosis-related responses, cell cycle progression, and BCL-2/ERK1/2/NF-κB-associated signaling pathways in THP-1 cells. These findings provide preliminary in vitro evidence supporting further preclinical evaluation of VEN-PEG-PLGA na-noparticles in AML models.

Abstract: Background/Objectives The accurate estimation of glomerular filtration rate (GFR) is essential for assessing trends in the prevalence (CKD), yet standard serum creatinine (SCr)-based estimates (eGFR_SCr) are limited by individual variations in muscle mass. While demographic surrogates like age and sex are typically used to account for these variations, they often lead to eGFR misclassification in individuals. This study investi-gated whether normalizing SCr to Dual-energy X-ray absorptiometry (DEXA)-derived Lean Mass Index (LMI) improves the association with cardiometabolic risk. Methods We analyzed data from 11,143 adults (mean age 46.0 ± 17.2 years) in the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort. Individual SCr concentrations were normalized to sex- and age-specific LMI reference values to calculate LMI-adjusted eGFR (eGFR_LMISCr). The strength of associations between eGFR_SCr and eGFR_LMISCr with cardiometabolic risk factors (dyslipidemia, hypertension, pre-diabetes/diabetes, and metabolic syndrome) was compared using age- and sex-adjusted logistic regression with bootstrap resampling. Results While eGFR_SCr and eGFR_LMISCr were highly correlated (R2 = 0.897), LMI adjust-ment led to significant reclassification between CKD stages G1, G2, and G3a. eGFR_LMISCr demonstrated significantly stronger associations with dyslipidemia, arterial hyperten-sion, pre-diabetes/diabetes, and metabolic syndrome compared to standard eGFR_SCr. Longitudinal analysis showed that LMI adjustment stabilizes eGFR change estimates, particularly in younger men. Conclusion Adjusting serum creatinine for LMI signifi-cantly enhances the epidemiological utility of GFR estimation. GFR_LMISCr improves car-diometabolic risk stratification, potentially offering a valuable method to "salvage" the utility and comparability of eGFR_SCr in historic cohorts in early-stage filtration impair-ment in settings where DEXA but not Cystatin C is available.

Abstract: Bladder cancer is one of the most common malignancies of the urinary tract and remains a major global health burden because of its high incidence, frequent recurrence, and substantial healthcare costs associated with lifelong surveillance. The disease exhibits remarkable clinical and biological heterogeneity, ranging from low-risk non–muscle-invasive bladder cancer (NMIBC) to highly aggressive muscle-invasive and metastatic urothelial carcinoma. Consequently, there is an urgent need for more accurate approaches to early diagnosis, individualized risk stratification, treatment selection, and long-term disease monitoring. Recent advances in artificial intelligence (AI), machine learning, and deep learning have created new opportunities to improve bladder cancer management across the entire continuum of care. AI-assisted approaches have demonstrated promising applications in cystoscopy, urine cytology, digital pathology, radiomics, and multimodal clinical decision support. These technologies have the potential to improve tumor detection, reduce interobserver variability, integrate heterogeneous clinical and molecular data, and generate individualized predictions of recurrence, progression, and therapeutic response. Despite encouraging progress, several important barriers continue to limit routine clinical implementation. Most published AI models are based on retrospective datasets, while external validation across diverse healthcare systems remains limited. Additional challenges include variability in imaging protocols and biomarker platforms, limited model interpretability, regulatory and ethical considerations, and integration into existing clinical workflows. Overall, AI has the potential to become an integral component of precision bladder cancer care. Continued development of large multicenter datasets, prospective clinical validation, standardized reporting, and seamless integration into routine clinical practice will be essential to fully realize the benefits of AI for improving diagnosis, risk prediction, treatment selection, survivorship, and long-term patient outcomes.

Abstract: Background/Objectives: Finerenone improves cardiovascular and renal outcomes in diabetic kidney disease (DKD), but hyperkalemia remains a key safety concern. Patients with elevated baseline potassium levels (≥ 4.9 mEq/L) are largely excluded from clinical trials, and real-world data in this population are scarce. Methods: In this retrospective multicenter cohort study derived from the FINE-TURK cohort, adults with DKD who initiated finerenone with baseline serum potassium ≥ 4.9 mEq/L were included. The primary outcome was clinically significant hyperkalemia (CSH) (≥ 5.5 mEq/L) within three months. Multivariable logistic regression analyses were used to identify associated factors, with multiple sensitivity analyses performed. Results: 166 patients were included, of whom 47 (28.3%) had baseline potassium levels between 5.1 to 5.5 mEq/L. Of the 166 patients, 35 (21.1%) developed CSH, and 10 (6%) patients had follow-up potassium ≥ 6.0 mEq/L. 126 (76.8%) patients required no intervention, 24 (14.6%) were initiated on potassium binders, and finerenone was discontinued only in 12 (7.3%) patients. Baseline eGFR, baseline urinary albumin, loop diuretic use and 20mg finerenone dose were associated with CSH. In contrast, baseline serum potassium was not associated with CSH. Conclusions: In patients with DKD and elevated baseline potassium levels, finerenone initiation was associated with manageable rates of hyperkalemia. Our findings support the cautious use of finerenone in selected patients under close monitoring, as well as highlight the need for a multidimensional approach to hyperkalemia risk assessment.

Abstract: Background: Sarcopenia is highly prevalent among older adults with chronic kidney disease (CKD) and is associated with adverse clinical outcomes. The finger-ring (Yubi-wakka) test is a simple anthropometric screening tool based on calf circumference; however, its performance in older adults with CKD remains unclear. This study aimed to investigate the association of the finger-ring test with low muscle mass, sarcopenia, and comprehensive geriatric assessment parameters and to evaluate its diagnostic performance for identifying low muscle mass in older adults with CKD. Methods: This cross-sectional study included 115 patients aged ≥65 years with CKD who were evaluated in geriatric and nephrology inpatient services. After excluding two participants with missing finger-ring measurements, 113 individuals were analyzed. Muscle mass was assessed using bioelectrical impedance analysis and low muscle mass was defined according to EWGSOP2-based Turkish cut-off values. Demographic characteristics, anthropometric measurements, laboratory findings, and comprehensive geriatric assessment parameters were recorded. Correlation analyses, logistic regression models, receiver operating characteristic (ROC) analyses, and likelihood-ratio tests were performed. Results: Among 113 participants, 62 were classified as finger-ring positive (FR=0) and 51 as finger-ring negative (FR=1). Low muscle mass was significantly more frequent in the FR=0 group than in the FR=1 group (51.6% vs. 24.0%, p=0.005). Finger-ring test results showed strong correlations with calf circumference (rho=0.689, p< 0.001) and body mass index (BMI) (rho=0.631, p< 0.001), whereas the correlation with muscle mass was modest (rho=0.250, p=0.008). For detecting low muscle mass, the finger-ring test demonstrated an area under the curve (AUC) of 0.643 (95% CI 0.554–0.732), sensitivity of 72.7%, specificity of 55.9%, positive predictive value of 51.6%, and negative predictive value of 76.0%. In multivariable analyses, BMI remained the strongest independent determinant of finger-ring test results, whereas the association with muscle mass lost statistical significance after BMI adjustment. Adding age and sex significantly improved discrimination, while the contribution of nutritional status was limited. Conclusions: The finger-ring test is associated with low muscle mass in older adults with CKD; however, its diagnostic performance is modest and appears to be substantially influenced by body size and calf circumference. Therefore, the finger-ring test should be considered a simple adjunctive screening tool rather than a stand-alone method for identifying low muscle mass in this population.

Abstract: Background: The widespread success of antiretroviral therapy (ART) has transformed HIV into a chronic condition, shifting clinical attention toward aging-associated comorbidities, including autoimmune and rheumatologic diseases. However, the epidemiology, clinical spectrum, and treatment outcomes of these conditions in older people living with HIV (PLH) remain incompletely characterized. Objective: This scoping review aimed to map contemporary evidence on autoimmune and rheumatologic diseases in aging PLH in the ART era, with emphasis on epidemiology, clinical phenotypes, diagnostic challenges, and therapeutic outcomes. Methods: A systematic search of PubMed, Embase, and Scopus was conducted for studies published from January 1, 2021, onward. Eligible studies included adult PLH with autoimmune or rheumatologic conditions and were screened according to PRISMA-ScR methodology. Case reports, non-human studies, and studies published before 2021 were excluded. Data were extracted narratively from included studies. Results: The search yielded 438 records, of which 134 duplicates were removed. After title, abstract, and full-text screening, 8 studies were included. The evidence identified a heterogeneous spectrum of autoimmune and rheumatologic manifestations in PLH, including systemic lupus erythematosus, reactive arthritis, psoriatic arthritis, rheumatic heart disease, immune thrombocytopenia, renal immune-mediated pathology, and myasthenia gravis. Contemporary data suggest that biologic and targeted small-molecule therapies are generally effective and well tolerated in selected PLH, although opportunistic infections and transient viral load increases have been reported with some agents. Conclusion: Autoimmune and rheumatologic diseases in aging PLH represent an emerging ART-era challenge. Prospective studies and multidisciplinary guidelines are needed to optimize diagnosis and treatment.

Abstract: Autoimmune rheumatic diseases are still treated predominantly through broad or targeted suppression of inflammatory pathways, yet durable restoration of self-tolerance remains a central unmet therapeutic goal. This narrative review examines restoration of immune tolerance as an emerging translational framework in rheumatology, integrating checkpoint agonism, antigen-specific immunotherapy, regulatory cell-based strategies, and immune-reset approaches within a unified therapeutic perspective. Rather than treating these strategies as isolated innovations, the review evaluates how each attempts to restore, reinforce, or reconfigure immune restraint at distinct biological levels, spanning inhibitory receptor signaling, antigen-selective non-responsiveness, dominant regulatory control, and deeper reconfiguration of pathogenic immune architecture. Their relevance is considered across rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, and systemic sclerosis, with emphasis on mechanistic rationale, translational maturity, disease-specific therapeutic fit, biomarkers, therapeutic timing, and major barriers to clinical implementation. Collectively, these approaches suggest a shift in rheumatology from repeated control of inflammatory consequences toward more selective and potentially durable recalibration of autoreactive immunity. Although the field remains biologically and clinically immature, restoration of immune tolerance is emerging as an important organizing principle for the development of more precise and potentially disease-modifying therapies in autoimmune rheumatic disease.

Abstract: Objectives: Streptococcus pneumoniae is a major respiratory pathogen. Reports during the COVID-19 era suggest decreased pneumococcal activity. This study aimed to assess the frequency of S. pneumoniae in adult sputum cultures and its antimicrobial susceptibility in a tertiary care hospital. Materials and Methods: This retrospective laboratory-based study was conducted in a tertiary care hospital in Turkey. Sputum cultures from adult patients between October 1, 2021, and October 1, 2023, were analyzed. Demographic, clinical, and antimicrobial susceptibility data of culture-confirmed cases were obtained from medical records. Results: Among 3,433 sputum cultures, only three (0.087%; 95% CI: 0.018%–0.255%) yielded S. pneumoniae. All patients were male with comorbidities such as cardiovascular disease, COPD, or diabetes. Pneumonia developed during hospitalization for non-infectious conditions. All isolates were susceptible to fluoroquinolones, rifampicin, tetracycline, and ceftriaxone; one showed resistance to macrolides and clindamycin. No multidrug resistance was detected. Conclusion: An extremely low pneumococcal isolation rate was observed during the COVID-19 and post-pandemic period. These findings align with global reports of reduced pneumococcal activity. Continued surveillance is essential to monitor epidemiological trends and resistance patterns.

Abstract: Background/Objectives: Acute pulmonary embolism (PE) is a major cause of cardio-vascular mortality, with prognosis influenced by hemodynamic status, comorbidities, and biomarker profiles. Although several laboratory markers have demonstrated prog-nostic relevance in PE, it remains unclear whether their predictive performance differs in patients with active malignancy. This study aimed to identify laboratory predictors of in-hospital mortality in acute PE and to evaluate the modifying effect of malignancy on biomarker-based prognostic stratification. Methods: This retrospective multicenter cohort study included 2803 consecutive patients with computed tomography-confirmed acute PE enrolled in the Regional Pulmonary Embolism Registry (REPER) between January 2015 and April 2026. Univariate and multivariable logistic regression analyses were performed to identify predictors of in-hospital mortality in the overall cohort and in subgroups stratified by malignancy status. Interaction analyses were used to assess effect modification by malignancy. Results: Active malignancy was present in 14.02% of patients, while overall in-hospital mortality was 14.93%. In the overall cohort, multivariable analysis identified malignancy (OR 1.698, 95% CI 1.128–2.555, p = 0.011), C-reactive protein (CRP), glucose, creatinine clearance (CrCl), platelet count, and white blood cell count as independent predictors of in-hospital mortality (BNP was excluded from multivariable models due to missing data). Mortality was significantly higher in patients with ma-lignancy compared with those without (20.9% vs. 13.2%, p < 0.001). In patients with malignancy, CRP and glucose remained independent predictors, whereas in non-malignant patients, CRP, glucose, and CrCl were independently associated with mortality. Significant interaction effects were observed for CrCl, age, glucose, and white blood cell count. Conclusions: Malignancy is an important predictor of in-hospital mortality in acute PE and may partially influence the prognostic performance of certain conventional biomarkers. These findings suggest that while standard risk markers remain broadly reliable, specific parameters might benefit from a cautious, malignancy-aware interpretation.