Medicine and Pharmacology

Abstract: Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 30% to 50%. Methods: This review synthesizes peer-reviewed literature on the virological, pathophysiological, clinical, and therapeutic aspects of HPS, with emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, prioritizing original research, clinical series, and controlled trials published through 2025. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and hantavirus IgM serology or RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure.

Abstract: Background: Interactions between the intestinal mycobiome and systemic metabolic regulation remain insufficiently characterised. While fungal colonisation is common in diabetes, its role in dynamic, event-driven dysglycaemia has not been defined. In particular, the impact of fungal morphological plasticity and biofilm formation under hyperglycaemic conditions remains unclear. Case Presentation: We report a 43-year-old female with a 25-year history of autoimmune insulin-dependent diabetes mellitus, characterised by refractory hyperglycaemia and chronic passage of high-volume, gelatinous, mucus-dominant intestinal material. Microbiological analysis confirmed Candida albicans with both yeast and hyphal forms. Episodes of evacuation were consistently preceded by extreme hyperglycaemia (>500 mg/dL) and followed by rapid declines to hypoglycaemic levels (<60 mg/dL). A 7-day observational log demonstrated reproducible glucose reductions ranging from 247 to >465 mg/dL per episode. Despite insulin therapy, glycaemic control remained unstable and was associated with systemic manifestations including pruritus, dehydration, and neuroenteric symptoms. Mechanistic Interpretation: We propose that chronic intestinal accumulation of a mucus-integrated fungal biofilm functions as a dynamic immunometabolic compartment. Hyperglycaemic conditions likely promote Candida albicans yeast-to-hypha transition via glucose-sensitive pathways, including cAMP–PKA and MAPK signalling, facilitating biofilm formation and persistence. Biofilm-associated β-glucans and mannans activate pattern recognition receptors such as Dectin-1 and Toll-like receptors, driving NF-κB and JNK-mediated inflammatory signalling. This results in inhibitory serine phosphorylation of IRS-1, impaired PI3K–AKT signalling, and functional insulin resistance. Accumulation of the biofilm amplifies this state, while threshold-triggered evacuation abruptly reduces inflammatory signalling, restores insulin sensitivity, and unmasks the pharmacodynamic effect of circulating insulin, resulting in rapid glucose decline.Conclusion: This case supports the proposal of a candidate syndrome, Candida-Associated Gut Biofilm–Driven Refractory Dysglycaemia Syndrome (CGB-RDS), characterised by reversible, compartment-driven insulin resistance and threshold-dependent metabolic switching. These findings highlight a previously unrecognised gut–mycobiome–metabolic axis and warrant further investigation into biofilm-mediated regulation of systemic glucose homeostasis.

Abstract: Objectives: Histologic grade is an important prognostic factor in hepatocellular carcinoma (HCC). Gd-EOB-DTPA-enhanced MRI may provide noninvasive im-aging markers related to tumour differentiation. This study aimed to evaluate the association of Gd-EOB-DTPA-enhanced MRI features, together with the albu-min-bilirubin (ALBI) score and alpha-fetoprotein (AFP), with HCC histologic grade and to assess the performance of combined predictive models. Methods: Methods: In this prospective cross-sectional study, 75 patients (mean age, 56.4 years; 66 men) with 88 histopathologically confirmed HCC lesions were en-rolled. Patients were classified into well-differentiated (grade I–II, n = 24) and poorly differentiated (grade III–IV, n = 51) groups according to the Edmondson–Steiner system. MRI was performed on a 1.5-T scanner and included T1-weighted in-phase/opposed-phase imaging, T2-weighted imaging, diffu-sion-weighted imaging, and dynamic Gd-EOB-DTPA-enhanced sequences, in-cluding arterial, portal venous, transitional, and 20-min hepatobiliary phases. Two radiologists, blinded to pathology, assessed predefined imaging features, and the lesion-to-liver ratio (LLR) was measured. Group comparisons were per-formed using Student’s t-test, the Mann–Whitney U test, and the chi-square or Fisher’s exact test, followed by multivariable logistic regression and ROC analy-sis with 500 bootstrap resamples. Results: Compared with well-differentiated HCC, poorly differentiated HCC showed a higher frequency of peritumoral hepatobiliary phase (HBP) hypointensity (62.7% vs. 4.2%, p < 0.001) and peritu-moral arterial hyperintensity (39.2% vs. 0%, p < 0.001). In multivariable analysis, peritumoral HBP hypointensity remained independently associated with poorly differentiated HCC (OR = 30.89, p = 0.002). The 2-parameter MRI model, includ-ing peritumoral HBP hypointensity and HBP tumour signal, yielded an AUC of 0.84. The combined MRI + ALBI + AFP model showed the highest discriminative performance, with an AUC of 0.87 and an accuracy of 78.7%. Conclusions: Con-clusions: Gd-EOB-DTPA-enhanced MRI features, particularly peritumoral HBP hypointensity, were associated with high histologic grade in HCC. In this cohort, combining MRI features with ALBI grade and AFP yielded higher discriminative performance than the MRI-only model. These findings may support preoperative histologic risk stratification, although external validation is required.

Abstract: Background: Non-small cell lung cancer (NSCLC) is driven by distinct oncogenic al-terations with important therapeutic and prognostic implications. Noninvasive bi-omarkers that predict molecular status in surgically resectable disease may aid in their management. We investigated the association of preoperative primary-tumor SUVmax on PET/CT, smoking history, and corrected serum calcium levels with driver oncogenic alterations and PD-L1 expression in surgically resected NSCLC. Methods: We retrospectively studied 170 patients with surgically resected NSCLC at a single tertiary center. Resected tumors were assessed for EGFR, KRAS, and BRAF mu-tations, ALK and ROS1 rearrangements, and PD-L1 expression. Associations between molecular status, PD-L1 expression, and clinicometabolic parameters were evaluated using univariate analyses and multivariable regression models. Results: A driver alteration was detected in 51.2% of tumors, and 30% of evaluable cases showed high PD-L1 expression (≥50%). Corrected serum calcium was positively correlated with SUVmax and emerged as the strongest independent predictor retained in the final linear regression model, with pack-years also contributing independently. Most molecular subgroups did not show significant differences in SUVmax. EGFR-mutated tumors showed a trend toward lower SUVmax compared with EGFR wild-type tumors, although this did not reach statistical significance. Smoking history was not significantly associated with PD-L1 expression, and pack-years did not differ significantly across the molecular groups examined. Conclusions: In this cohort of surgically resected NSCLC, preoperative corrected se-rum calcium and smoking exposure were more closely associated with tumor meta-bolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

Abstract: Background: Type 1 diabetes mellitus (T1D) is associated with chronic inflammation, platelet activation, and increased cardiovascular risk (CVR). The relationships between adipokines and platelet indices in long-standing T1D remain incompletely defined. Objective: To explore the relationships between adipokines (adiponectin and leptin), platelet indices, and inflammatory status in adults with long-standing T1D. Methods: This cross-sectional study included 124 adults with long-standing T1D and 59 non-diabetic controls. Platelet indices were obtained from automated blood count, and serum leptin (LEP), adiponectin (ADNC), and C-reactive protein (CRP) were measured using standardized assays. Associations were evaluated using correlation and multivariable regression analyses with adjustment for body mass index (BMI). Results: Platelet count (PLT) and plateletcrit (PCT) were higher in T1D compared with non-diabetic individuals (p=0.003 for both), while mean platelet volume (MPV) and platelet distribution width (PDW) showed non-significant upward trends. ADNC levels were higher in T1D (p< 0.001), whereas LEP and the leptin–adiponectin ratio (LAR) did not differ between groups. In T1D, LEP correlated with PLT (rho=0.235), PCT (rho=0.263), and CRP (rho=0.474), all p< 0.05. Similar associations were observed for LAR. No significant associations were found in non-diabetic controls. In multivariable analyses, PCT remained associated with LEP in T1D after adjustment for BMI, whereas in the control group LEP was associated with BMI only. Conclusion: LEP and platelet-related indices were associated in individuals with long-standing T1D, whereas ADNC showed no such relationships. These findings suggest a distinct pattern of adipokine–platelet associations in long-standing T1D.

Abstract: Background: Heme oxygenase (HO) is an antioxidant enzyme ubiquitously present in the body. Oxidative stress is one of the main causes of male infertility. Here, we aimed to analyze the correlation between serum heme oxygenase-1 (HO-1) level and sperm count, motility, normal morphology, and sperm DNA fragmentation index (DFI) in infertile male patients. Methods: In this retrospective cross-sectional study, serum HO-1 concentrations, routine semen parameters, sperm morphology, and DFI were analyzed in 178 patients. Subjects were stratified into high-HO-1 (≥278 ng/L; n=77) and control (<278 ng/L; n=101) groups. Intergroup comparisons and Spearman's correlation analyses were performed. Results: The high-HO-1 group demonstrated significantly increased normal sperm morphology (P<0.05) and reduced sperm DFI (P<0.05) versus controls. No significant intergroup differences existed in sperm concentration or progressive motility (P>0.05). Correlation analysis revealed positive associations between HO-1 levels and normal morphology (r=0.190, P<0.05), and negative correlations with DFI (r= -0.195, P<0.05).Conclusions: We first identified significant correlations between serum HO-1 levels and both sperm DFI and normal morphology in infertile men, suggesting HO-1's protective role in spermatogenesis. Serum HO-1 quantification may offer a novel strategy for male fertility assessment.

Abstract: Background/Objectives: The Child-Pugh system is widely used to grade cirrhosis severity but includes clinical components that may be variably documented. This study evaluated the association and diagnostic performance of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and albumin-bilirubin (ALBI) score for discriminating Child-Pugh classes in cirrhosis. Methods: We conducted a retrospective cross-sectional study using medical records from 302 adults with cirrhosis treated at Thai Binh General Hospital, Vietnam, from January to June 2025. Child-Pugh class was reconstructed from bilirubin, albumin, PT%, ascites, and hepatic encephalopathy. APRI, FIB-4, and ALBI were calculated from routine laboratory data. Group comparisons, correlation analysis, multivariable regression, receiver operating characteristic analysis with bootstrap 95% confidence intervals, optimal cut-offs, and reclassification metrics were assessed. Results: Among 302 patients, 48 (15.9%) were Child-Pugh A, 120 (39.7%) Child-Pugh B, and 134 (44.4%) Child-Pugh C. ALBI values differed consistently across Child-Pugh classes (-2.23 ± 0.37, -1.65 ± 0.45, and -0.80 ± 0.46; p < 0.001), whereas APRI and FIB-4 showed less distinct separation between classes. ALBI showed a strong correlation with the Child-Pugh score (r = 0.853, p < 0.001) and remained associated with Child-Pugh severity in multivariable linear and logistic regression models. Among the three indices, ALBI showed the highest discrimination for Child-Pugh B/C versus A in this cohort (AUC, 0.919; 95% CI, 0.884-0.950), with an estimated optimal cut-off of -1.753. Conclusions: In this retrospective cohort, ALBI showed closer agreement with Child-Pugh severity and higher discrimination for Child-Pugh B/C versus A than APRI and FIB-4. ALBI may be considered as a simple laboratory-based adjunct to support Child-Pugh stratification in routine cirrhosis assessment, but further prospective validation is required before broader clinical application.

Abstract: Bioelectrical impedance analysis (BIA) is a widely used technique in clinical and research settings because it provides non-invasive estimates of body composition. However, the quality of a measurement depends on more than the perceived accuracy and precision of numbers produced by a BIA device. This review considers BIA through the lens of metrology, defined as the science of measurement. It highlights several key factors that affect measurement quality. These include accuracy, precision, calibration, standardisation, and uncertainty quantification, all of which are essential for meaningful, clinically feasible BIA measurements. Applying prediction equations generated by the device outside their intended context, poor electrode placement, or uncalibrated devices can introduce bias, whereas biological variability can complicate the interpretation of bioimpedance results. The traditional emphasis on using a reference method for validation is considered along with clinical relevance, which is argued to be an equally important benchmark for evaluating measurement utility. We also present best practices and practical guidelines for improving measurement quality, interpretation, and integration into clinical workflows. By adopting a metrological mindset in clinical practice and treating BIA with the same rigour as other diagnostic tools, its utility in areas such as fluid management, nutrition, and preventive health can be further enhanced. Trustworthy decisions depend not only on the data itself but also on how it is measured, interpreted, and used.

Abstract: Prolonged contact between oral mucosa and dental amalgam restorations may influence local epithelial homeostasis, although the immunohistochemical profile of clinically non-dysplastic mucosa exposed to long-term restorative materials remains insufficiently defined. This study investigated histopathological remodeling and the expression patterns of cytokeratin 19 (CK19), Ki67, and p53 in oral mucosal specimens adjacent to long-standing amalgam restorations. A total of 108 specimens were retrospectively analyzed, including 78 samples from mucosa in direct contact with amalgam restorations and 30 control specimens without amalgam exposure. Exposed cases were categorized according to contact duration: 5–10 years, 11–20 years, and ≥21 years. Epithelial and stromal changes were semi-quantitatively assessed, and immunohistochemical staining was evaluated using predefined scoring criteria. An exploratory Integrated Epithelial Remodeling Score (IERS), combining basal hyperplasia, inflammatory infiltrate, CK19 distribution, and Ki67 proliferative index, was used to estimate cumulative remodeling intensity. Longer amalgam exposure was significantly associated with increased inflammatory infiltrate, basal epithelial expansion, suprabasal CK19 expression, and higher Ki67 labeling indices (all p &lt; 0.001). CK19 redistribution showed positive associations with both inflammatory intensity and epithelial proliferative activity. IERS values differed significantly among exposure groups (p &lt; 0.001), with more pronounced remodeling in intermediate- and long-duration exposure categories. p53 expression showed statistically detectable but heterogeneous variation. No epithelial dysplasia was observed. These findings suggest that long-term contact with dental amalgam restorations is associated with a coordinated, non-dysplastic remodeling phenotype of the oral mucosa, characterized by inflammatory activation, CK19 redistribution, and reactive proliferative reinforcement. In this context, suprabasal CK19 expression may reflect adaptive epithelial plasticity rather than preneoplastic transformation.

Abstract: Background: Chronic kidney disease (CKD) is characterized by accelerated aging and decline in physical function. Klotho, an anti-aging protein predominantly expressed in the kidney, plays a crucial role in mineral metabolism and longevity. Exercise has been proposed as a non-pharmacological strategy to enhance Klotho expression; however, clinical evidence in hemodialysis patients remains limited. Objective: This study aimed to explore the association between exercise and plasma Klotho levels using a combined case study and cross-sectional design. Methods: This study included: (1) A prospective case study evaluating the effects of high-intensity interval training (HIIT) in a hemodialysis patient. (2) A cross-sectional analysis comparing plasma Klotho levels between hemodialysis patients (n=24) and healthy controls (n=18) and assessing their association with habitual physical activity. Plasma Klotho levels were measured using ELISA. Statistical analyses included the Mann–Whitney U test and Spearman’s correlation coefficient. Results: In the case study, improvements in muscle strength and exercise tolerance were observed following HIIT, allowing the patient to resume daily occupational activities. In the cross-sectional analysis, plasma Klotho levels were significantly lower in hemodialysis patients than in healthy controls (p=0.0001). A moderate positive correlation was observed between exercise habits and plasma Klotho levels in hemodialysis patients (r=0.52, p=0.02), whereas no significant association was found in healthy individuals. Conclusion: These findings suggest that exercise therapy may exert potential anti-aging implications in hemodialysis patients through modulation of Klotho expression. This study provides translational evidence linking clinical rehabilitation and molecular aging pathways.

Abstract: While joint hypermobility can result from various medical conditions, it is most commonly associated with a group of related genetic conditions that affect connective tissue known as Ehlers–Danlos syndromes (EDSs). As there is currently no specific genetic testing for the diagnosis of Ehlers–Danlos hypermobility syndrome (hEDS), diagnosis is strictly made based on clinical criteria, which include physical features such as pain and family history, in addition to a scoring system known as the Beighton Score—a 9-point scale used to measure joint hypermobility—with a score of >4 considered significant. While hEDS often causes chronic muscle and joint pain, the underlying mechanisms remains poorly understood. Dysautonomia, characterized by common symptoms such as anxiety, vertigo, and increased heart rate when standing (orthostatic intolerance), in addition to multiple gastrointestinal symptoms, is highly prevalent among hEDS patients. We hypothesize that hypermobility due to ligamentous instability of the upper cervical spine, C1 and C2, results in impingement of the carotid sheath, the carotid artery and, more significantly, the vagus nerve, thus explaining the myriad symptoms that accompany hEDS. We also propose the novel use of extracorporeal shock wave therapy (ESWT) to treat this instability.

Abstract: We conducted a literature review to evaluate global antifungal susceptibility patterns in Candida auris, an emerging multidrug-resistant fungal pathogen of growing clinical concern. A comprehensive search of the literature identified 29 studies reporting min-imum inhibitory concentrations (MICs) and resistance rates across major antifungal classes. Across studies, C. auris demonstrated consistently high resistance to fluconazole, with variable resistance observed among other azoles, amphotericin B, and echi-nocandins, alongside evidence of emerging multidrug resistance. These findings reflect significant geographic variability and highlight ongoing challenges in treatment selec-tion due to inconsistent susceptibility profiles and limited standardized breakpoints. Emerging antifungal agents, including ibrexafungerp and manogepix, demonstrate promising activity and may help address current therapeutic gaps. Overall, the global rise in antifungal resistance among C. auris isolates underscores the narrowing range of effective therapeutic options and reinforces the need for continued surveillance, improved susceptibility testing standardization, and development of novel antifungal agents.

Abstract: Background: Traditional cardiovascular risk models often overlook "residual risk" driven by psychopathological factors. This study investigates the independent and in-cremental predictive value of Type D personality (TDP) and specific symptomatic di-mensions on long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We prospectively evaluated 221 patients with confirmed CAD. An-atomical complexity was quantified via the SYNTAX Score (SS). Psychological profil-ing utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1,026 days using multivariate Cox proportional hazards models. Results: TDP prevalence was 33.0% and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; p < 0.001). In the integrated psychological model, Anxiety emerged as a signifi-cant independent predictor of survival (HR = 0.941; p = 0.049). This suggests an "Anxi-ety Paradox," where heightened vigilance may improve outcomes. The psychological model demonstrated superior predictive accuracy (C-index = 0.624) compared to the clinical model (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress (e.g., depression: r = 0.493). Conclusions: TDP and granular psychological symptoms are robust, independent determinants of mortality that transcend anatomical severity. TDP acts as a marker of biological vulnerability and accelerated vascular aging, while manageable anxiety may enhance treatment adher-ence. Integrating systematic psychological screening into routine CAD care is essential for refined risk stratification and improved long-term survival.

Abstract: Because of its anatomical complexity, the cervical spine is highly susceptible to injury, especially the blunt acceleration/deceleration trauma of which the most frequent mechanism, is “whiplash”, commonly referred to as Whiplash Associated Disorder (WAD). Despite this knowledge the significance and complexity of whiplash injuries are widely underestimated. This underestimation of the significance of this injury is the widely held belief that it is a benign self-limiting soft tissue injury that frequently has monetary gain attached. This negative framing of the injury which has largely been shaped by the insurance industry rather than by clinicians frequently causes medical providers to view the injury with skepticism. Adding to the problem faced by clinicians are the more recently imposed guidelines for diagnosing and treating acute whiplash, especially in the area of imaging that has placed both the provider and the patient at increased risk.

Abstract: Introduction Liver transplantation is currently an increasingly popular treatment method for patients with liver failure, both in adults and children. Antibody-mediated rejection (AMR), which is a very rare and poorly understood phenomenon, can lead to deterioration of graft function. The aim of the study was to analyze the clinical and histopathological manifestation of AMR in pediatric patients. Material and methods Sixty-two liver core biopsies from forty-two pediatric patients were included in this retrospective study. AMR was diagnosed in 7 children (in 10 biopsies), 35 demonstrated features of acute T-cell mediated rejection (TCMR) in 52 biopsies. C4d binding assay was performed in all biopsies using the immunohistochemical (IHC) method. The specimens were re-evaluated for signs of acute and chronic rejection, bilirubinostasis, and steatosis. Fibrosis was evaluated using a 6-grade Ishak scale. The Banff classification was used to assess TCMR activity. Evaluation of AMR was performed according to a newly developed original histopathological grading. Relationship between histopathological grading and morphological, as well as laboratory parameters was determined in each group depending on type of rejection. Statistical analysis was performed according to standard indications. Results The median age of patients (months) at the time of biopsy was 47.6 (15.03 – 98.83) and the median time from transplantation (months) was 0.9 (0.3 – 7.6). Results of the study brought evidence that histopathological lesions were the least specific manifestation suggesting AMR. Positive result of C4d staining with or without associated morphological abnormalities statistically increases the likelihood of AMR diagnosis. No statistically significant correlation was found between the type of rejection and laboratory tests. Conclusions: Diagnosis of AMR in transplanted liver is complicated and need to be complex. However, the proposed histopathological grading may be a helpful method for selecting patients who should be assessed for Donor-specific antibodies (DSAs) or in whom AMR should be suspected when DSA cannot be determined.

Abstract: The diverse clinical manifestations of allergic skin diseases often overlap with other pathologies, posing significant diagnostic challenges. Allergen-specific IgE (sIgE) testing is essential for identifying triggers and personalizing treatments in allergic skin diseases. A retrospective study was conducted on 4,277 medical records of patients with allergic skin diseases who underwent sIgE testing at the HCMC Hospital of Dermato-Venereology, a tertiary referral dermatology center serving Southern Vietnam, from January to December 2024. The results revealed that 64.09% of the patients exhibited sIgE sensitization. House dust mites (D. farinae: 30.91%, D. pteronyssinus: 25.67%) and fire ants (24.06%) were the predominant allergens. Food sensitization was predominantly mild, with almond being the most common (10.26%). Significantly higher sensitization severity was observed in males, young adults (12–35 years), and non-urban residents (p &lt; 0.001). Correlation analysis demonstrated robust co-sensitization and cross-reactivity among aeroallergens, predominantly driven by house dust mites. In conclusion, allergen sensitization profiles are strongly influenced by demographic and geographic factors, with a characteristic pattern observed in Southern Vietnam. Multiplex sIgE testing provides substantial value in disease stratification, prognostic assessment, and the development of personalized treatment strategies in this tropical setting.

Abstract: Background: COVID-19 not only primarily affects the respiratory system, but renal involvement is increasingly recognized. Prerenal acute kidney injury (AKI) is a common and potentially reversible complication driven by hypovolemia, hypoxia, systemic inflammation, and hemodynamic instability.Case Presentation: A 60-year-old male presented with fever, dry cough, dyspnea, oliguria, and generalized weakness. Laboratory findings revealed elevated blood urea nitrogen and serum creatinine, a high BUN/creatinine ratio, low urine sodium (18 mmol/L), high urine osmolality (650 mOsm/kg), and a low fractional excretion of sodium (0.67%), consistent with prerenal AKI. Chest imaging suggested viral pneumonia, and RT-PCR confirmed COVID-19 infection. Renal ultrasonography showed normal kidney structure with reduced renal perfusion. The patient was diagnosed with stage II prerenal AKI secondary to COVID-19. Management included oxygen therapy, prompt fluid resuscitation with lactated Ringer’s solution, anticoagulation, and supportive care. Renal function and urine output improved within 48 hours without the need for renal replacement therapy.Conclusion: COVID-19 can precipitate prerenal AKI through hypovolemia, hypoxia, and inflammation-mediated hemodynamic disturbances. Early diagnosis using urinary biomarkers and prompt fluid resuscitation can lead to complete renal recovery.

Abstract: The renin–angiotensin–aldosterone system (RAAS) is a central regulator of blood pressure and fluid homeostasis. However, its dysregulation contributes to the development of cardiovascular and chronic kidney diseases, including hypertension, diabetes, and metabolic disorders. The identification of the prorenin receptor (PRR) has expanded the understanding of RAAS, revealing functions beyond its classical role in angiotensin II (Ang II) generation. In this review, we provide an updated and integrative overview of PRR biology, emphasizing its multifunctional roles in both Ang II–dependent and independent signaling. PRR also functions as an accessory component of the vacuolar H⁺-ATPase and participates in key intracellular pathways, including ERK1/2-MAPK, PI3K/Akt, and Wnt/β-catenin. Through these mechanisms, PRR contributes to cardiovascular remodeling, renal inflammation and fibrosis, metabolic dysregulation, and angiogenesis. Emerging evidence further identifies the soluble form of PRR (sPRR) as a biologically active circulating factor with endocrine-like properties. Clinical and experimental studies suggest that sPRR serves as both a biomarker and a mediator linking tissue RAAS activation to systemic cardiorenal and metabolic disease progression. Collectively, this review highlights PRR as a central molecular hub that integrates extracellular hormonal signals with intracellular metabolic and inflammatory pathways, underscoring its relevance in the pathophysiology of cardiovascular, renal, and metabolic diseases.

Abstract: Background: Adults with congenital heart disease (CHD) are at markedly increased risk of infective endocarditis (IE); however, data comparing clinical characteristics and outcomes in sur-gically treated IE patients with and without CHD remain limited. This study aimed to evaluate differences in clinical profile, microbiology, complications, and outcomes be-tween these groups. Methods: We conducted a retrospective cohort study of 773 adult patients who underwent surgery for IE at a tertiary center in China between October 2013 and August 2025. Patients were categorized into CHD (n = 188) and non-CHD (n = 585) groups. Baseline characteristics, microbiological findings, operative data, and postoperative outcomes were compared. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline differences. Long-term survival was assessed using Kaplan–Meier analysis. Results: Patients with CHD were significantly younger and had fewer cardiovascular comorbid-ities than non-CHD patients. CHD was associated with a higher prevalence of right-sided and multivalvular infection, whereas non-CHD patients predominantly had left-sided disease. Streptococcus species were the most common pathogens in both groups, with no significant intergroup differences in microbiological profiles. After IPTW adjustment, no significant differences were observed in major postoperative complications, length of stay, or early mortality. Overall and in left-sided IE, long-term survival was comparable between groups, whereas in right-sided IE, patients with CHD exhibited significantly better long-term survival (HR = 0.17, 95% CI: 0.04–0.66, P = 0.01). Conclusions: Despite distinct clinical characteristics, adults with and without CHD undergoing surgery for IE had similar overall outcomes, although CHD was associated with better long-term survival in right-sided IE.

Abstract: Background: The coexistence of Myasthenia Gravis (MG) and Rheumatoid Arthritis (RA) represents a rare but clinically challenging form of polyautoimmunity, raising interesting questions about shared immunopathogenic mechanisms and the safety of long-term immunomodulatory therapies. Methods: The article describes a case report of a 66-year-old female with a 12-year history of seropositive RA who subsequently developed seropositive MG during long-term exposure to hydroxychloroquine (HCQ) therapy. Following discontinuation of HCQ, methotrexate (MTX) therapy was initiated and stable control of both diseases was temporally obtained. Results: Three years later, the patient presented with upper gastrointestinal bleeding and severe microcytic anemia. Further evaluation revealed advanced liver fibrosis (F4) and severe gastropathy, consistent with Child–Pugh class A cirrhosis. Viral, alcoholic, and autoimmune causes of chronic liver disease were excluded. In the absence of alternative etiologies, this was considered possibly associated with MTX therapy, in the context of additional metabolic risk factors, including type 2 diabetes mellitus and increased body mass index. Conclusions: The complex interplay between polyautoimmunity and treatment-related toxicity is underscored in this article. Overlapping autoimmune diseases may arise on a shared immunological background, while therapeutic agents may contribute to disease expression or long-term complications. These findings highlight the need for individualized therapeutic strategies and vigilant monitoring, particularly in patients with coexisting metabolic risk factors.