Search Results (14,020)

Approximately 795,000 people experience new or recurrent strokes in the United States each year; between 10 to 20% of these are spontaneous intracerebral hemorrhages (ICH). Uncontrolled hypertension is not only the most common cause of ICH but also a major risk factor for hematoma expansion. Resistant hypertension, defined as persistently elevated blood pressure despite the use of three or more antihypertensives of different classes, is common in patients with ICH. A long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), and a thiazide diuretic are generally considered the mainstay for the treatment of resistant hypertension. However, due to the risk of hyponatremia and worsening cerebral edema, thiazide diuretics should be avoided during the first few weeks of ICH. Recent evidence supports the use of a mineralocorticoid receptor antagonist. While resistant hypertension may be idiopathic, a workup of secondary causes should be pursued. Adequate and timely control of elevated blood pressure remains one of the main cornerstones of treatment in patients with ICH. Previous studies have revealed that resistant hypertension in patients with ICH is associated with longer ICU stays, a higher risk of recurrent stroke, and can contribute to renal, cardiac, and neurologic complications. This emphasizes the need for early initiation of oral antihypertensives and adequate blood pressure control at hospital discharge. Landmark studies have shown that early lowering of SBP to 130–150 mm Hg with smooth, sustained BP control is safe and may improve functional outcomes in patients with mild to moderate ICH. After initiating oral antihypertensives with a calcium channel blocker, an ACEi or ARB beta-blocker, and a mineralocorticoid receptor antagonist to maximally tolerated doses, the next line of antihypertensive treatment should be tailored to the patient’s co-morbidities, and may include a beta-blocker, central alpha agonist, hydralazine, and minoxidil. In this review, we discuss the epidemiology of resistant hypertension in ICH and its molecular basis, diagnostic workup, and acute and long-term treatment. We present novel mechanisms implicated in hypertensive ICH, including ferroptosis, neuroinflammation, the CNS–gut microbiome axis, and novel therapeutics. We also propose a simple algorithm for the optimal pharmacological management of resistant hypertension in ICH. Full article

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of >20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4–6.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan–Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk. Full article

(1) Background: Treatment of esophageal cancer (EC) traditionally consists of neoadjuvant radiochemotherapy (RCT) followed by resection; however, esophagectomy is associated with substantial morbidity, particularly in patients with relevant comorbidities. Therefore, a watchful waiting (WW) strategy has been increasingly adopted for patients achieving a complete response to RCT. This study aimed to identify independent predictors and recurrence patterns in EC patients managed with WW. (2) Methods: We retrospectively analyzed all patients with potentially curable EC and complete response to RCT treated at a tertiary university hospital between 2014 and 2022. Comprehensive staging and restaging were performed using computed tomography, endoscopy with ultrasound and biopsies, and positron-emission tomography, followed by structured surveillance. Recurrence patterns and associated clinical and tumor-related factors were assessed using multivariate regression analysis. (3) Results: Among 50 included patients, 30 (60%) developed recurrence after a median of 202 days. Patients with initially nodal-negative disease did not develop distant recurrence, whereas nodal-positive patients showed metastatic recurrence in 26% and local regrowth in 16%. (4) Discussion: Adenocarcinoma, circumferential tumor extent greater than 50%, dysphagia, fatigue, and deterioration of general condition at restaging were independently associated with recurrence. These findings support risk-adapted surveillance and may facilitate personalized management in EC patients undergoing WW. Full article

Background: Invasive Aspergillosis (IA) is a rare but life-threatening fungal infection in immunocompromised hosts, including solid organ transplant (SOT) recipients. While extensively studied in other SOT populations, data on IA in pancreas transplant (PT) recipients are limited. Earlier studies reported mortality rates nearing 100%, whereas more recent data show that 12-week mortality still exceeds 20% despite improvements in antifungal therapy. Current prophylaxis strategies for PT recipients mainly focus on Candida species, and there are no clear, standardized recommendations for Aspergillus prevention. Given the paucity of focused data, the epidemiology, clinical characteristics, and outcomes of IA in PT recipients are not well defined. This study aimed to assess the incidence, clinical characteristics, and outcomes of IA among hospitalized PT patients using a nationally representative dataset. Methods: We conducted a descriptive analysis using the National Inpatient Sample (NIS) from 2016 to 2020. PT admissions were identified using International Classification of Diseases, Tenth Revision (ICD 10) codes for transplant status and procedures. IA was defined using validated ICD 10 codes. Baseline demographics, hospital characteristics, comorbidities, and outcomes, including sepsis, acute kidney injury (AKI), acute respiratory failure (ARF), invasive mechanical ventilation (IMV), all-cause in-hospital mortality, length of stay, and total hospitalization costs and charges were compared between PT admissions with and without IA. National estimates were calculated using discharge weights, and comparisons were performed using the chi-square test and adjusted Wald test. Multivariable analysis was performed to identify predictors of all-cause in-hospital mortality among PT admissions complicated by IA. Two-sided p values < 0.05 were considered statistically significant. Results: Between 2016 and 2020, 65,980 PT-related hospitalizations were identified, of which 250 (0.4%) had IA. PT admissions complicated by IA were more commonly aged 41 to 60 years (59% vs. 46%, p = 0.012) and were less likely to have a Charlson Comorbidity Index greater than 3 (54% vs. 68.6%, p < 0.001) compared with PT hospitalizations without IA. The PT with the IA cohort had higher rates of sepsis (100% vs. 46.1%, p < 0.001), AKI (60% vs. 36.7%, p < 0.001), ARF (28% vs. 9.4%, p < 0.001), and IMV use (18% vs. 4%, p < 0.001) compared with the PT without the IA cohort. Among PT hospitalizations with IA, IMV use was independently associated with higher all-cause in-hospital mortality (adjusted odds ratio 48.777, p = 0.009). Overall, in-hospital mortality was significantly higher in PT hospitalizations with IA compared with those without IA (12% vs. 2%, p < 0.001). Mean length of stay was longer (24.86 vs. 6.13 days, p < 0.001), and total charges ($378,494 vs. $94,938, p < 0.001), and total costs ($93,019 vs. $24,463, p = 0.023) were significantly higher compared with PT hospitalizations without IA. Conclusion: Although rare, IA in PT recipients is associated with higher rates of sepsis, AKI, ARF, venous thromboembolism, prolonged hospitalization, increased mortality, and greater healthcare utilization. Despite the inherent limitations of administrative datasets, this nationally representative analysis highlights the substantial clinical and economic burden of IA in this high-risk population. These findings emphasize the need for targeted surveillance, early diagnosis, and evidence-based antifungal strategies in this vulnerable population. Full article

Ischemic stroke (IS) is associated with pronounced oxidative stress and lipid peroxidation, which contribute to secondary neuronal damage. This study explored the effects of a six-month intervention with a new formulation containing citicoline, vitamin C, and extracts from green tea and aronia (Cytodeox™) on arachidonic acid (AA) metabolism, lipid peroxidation assessed by total 8-iso-prostaglandin F₂α (8-iso-PGF₂α), and Sirtuin-1 (SIRT1) expression in healthy controls (n = 43) and patients with IS (n = 53), both with and without comorbidities. AA and 8-iso-PGF₂α were quantified in serum using UPLC–MS and ELISA, respectively, and the fold change in SIRT1 expression was assessed in peripheral blood mononuclear cells (PBMCs) by RT-qPCR. In healthy controls, Cytodeox™ significantly lowered AA and 8-iso-PGF₂α levels. IS patients showed markedly increased baseline 8-iso-PGF₂α, indicating severe oxidative stress. Following supplementation, 8-iso-PGF₂α levels increased in patients with comorbidities, particularly diabetes mellitus (DM), whereas an exploratory analysis suggested a decreasing trend in patients without comorbidities. SIRT1 expression was significantly upregulated in IS patients, with the most pronounced increase observed in the DM subgroup, while remaining unchanged in controls. These findings suggest a protective, antioxidant, and membrane stabilising effect of Cytodeox™ under conditions of preserved or moderately impaired redox homeostasis, supporting its potential role as a preventive or early supportive intervention. Full article

Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the pleasant sensation elicited by gentle pressure on a mouse’s nape. However, their potential role in mitigating pain and pain-related negative emotions in response to somatic stimuli remains unclear. Methods: A CFA-induced chronic pain and anxiety comorbidity model was established in C57BL/6J mice. In vivo calcium imaging of dorsal root ganglia (DRG) neurons in Mrgprb4-GCaMP6s transgenic mice characterized neuronal responses to transcutaneous electrical nerve stimulation (TENS) at the Zusanli (ST36) acupoint. Optogenetic activation (Mrgprb4-ChR2 mice) and viral ablation of Mrgprb4-lineage neurons were employed to evaluate their role in mediating TENS effects on mechanical pain thresholds and anxiety-like behaviors. Results: In vivo calcium imaging revealed that 0.5 mA TENS preferentially activated Mrgprb4-lineage neurons compared to 2.0 mA TENS. In CFA model mice, 0.5 mA TENS at ST36 significantly increased mechanical pain thresholds and reduced anxiety-like behaviors in the open-field test. Optogenetic activation of Mrgprb4-lineage neurons at ST36 replicated these analgesic and anxiolytic effects, demonstrating the sufficiency of these neurons for therapeutic outcomes. Conversely, viral ablation of L3–L5 Mrgprb4-lineage neurons substantially attenuated the therapeutic effects of 0.5 mA TENS for both pain relief and anxiety reduction, indicating their necessity in mediating TENS efficacy. Conclusions: Mrgprb4-lineage neurons serve as critical peripheral mediators of TENS-induced analgesia and anxiolysis. These findings identify a specific neuronal population underlying the therapeutic effects of somatic stimulation at ST36, providing mechanistic insights that may guide optimization of TENS parameters for treating chronic pain and comorbid anxiety in clinical settings. Full article

Introduction: Oncological therapies have significantly improved patient outcomes but are increasingly associated with renal toxicity, which can markedly influence therapeutic decisions. Integrating early identification of kidney injury into clinical workflows is essential for personalized medicine, allowing treatment tailoring based on individual risk profiles. Aim: To evaluate the incidence of acute kidney injury (AKI) and chronic kidney Disease (CKD); assess indices of renal function recovery in patients who developed AKI; and investigate the incidence of renal immune-related adverse events (irAEs) in patients receiving immunotherapy. Materials: Renal function, serum electrolytes, inflammatory markers, blood gas analysis, and urinalysis were evaluated at baseline before oncological therapy (T0), after approximately 2 weeks (T1), and after 3 months (T2). Results: Seventy patients were analyzed (median age 71.5 years). AKI occurred in 43 patients (61.4%) and CKD in 18 (25.7%). Patients receiving immunotherapy displayed significantly higher blood urea nitrogen (p < 0.01) and creatinine (p < 0.01) levels compared to those undergoing traditional therapies (targeted therapy and chemotherapy). Treatment discontinuation was required in 14 (56%) immunotherapy patients versus 7 (19.4%) receiving traditional therapy (anti-VEGF and cisplatin) (p < 0.01). Among 25 immunotherapy-treated patients, 13 (52%) developed immune-related adverse events (irAEs). Patients with irAEs predominantly experienced AKI (92.3%), whereas those without irAEs showed both AKI and CKD (44.4%) (p < 0.01). Treatment discontinuation occurred in 84.6% of patients with irAEs compared to 11.1% without irAEs (p < 0.001). Conclusions: We showed a high incidence of AKI and CKD among cancer patients; in particular, the majority of patients receiving immunotherapy presented irAEs. CKD also occurs in association with comorbidities, such as previous use of NSAIDs, investigations with contrast agents and episodes of AKI on CKD determined by drugs. It seems necessary for there to be multidisciplinary collaboration between oncologists and nephrologists to individualize treatment plans; thus allowing the non-suspension of therapy, which positively influences the prognosis of patients. Full article

Background: Chronic cocaine exposure is increasingly associated with persistent brain alterations, yet it remains unclear whether these changes reflect reversible neuroadaptation, accelerated brain ageing, or a degeneration-like trajectory in a vulnerable subgroup. This Perspective proposes a neuroprogressive vulnerability framework—referred to as cocaine-specific encephalopathy/cerebropathy only in a heuristic sense—to organise heterogeneous evidence without implying a distinct neurodegenerative disease entity. Methods: We conducted a structured, critical synthesis of peer-reviewed human and preclinical literature (PubMed, Scopus, Web of Science; inception to December 2025), integrating neuroimaging (MRI/DTI/fMRI/PET/SPECT), neuropathology/post-mortem findings, neurochemical and molecular mechanisms, and neuropsychological outcomes, with explicit attention to confounders (polysubstance use, psychiatric and medical comorbidity, HIV, vascular risk, abstinence duration). Results: Convergent evidence supports a multi-hit vulnerability model in which chronic stimulant exposure may weaken neural resilience through dopaminergic dysregulation, oxidative stress, mitochondrial dysfunction, neuroinflammatory signalling, and putative α-synuclein–related mechanisms. Human imaging studies consistently implicate fronto–striato–limbic circuits and suggest possible cerebellar involvement, but findings are heterogeneous and often cross-sectional; direct evidence of progressive neuronal loss or disease-defining proteinopathies attributable to cocaine remains limited. Conclusions: Rather than asserting cocaine-induced classic neurodegeneration, we outline an exploratory framework in which chronic cocaine exposure may increase susceptibility to neuroprogressive impairment in a subset of biologically vulnerable individuals. Longitudinal multimodal studies combining advanced imaging, biomarkers, and phenotypic stratification are needed to clarify causality, temporal progression, and reversibility with sustained abstinence. Full article

Psychological comorbidity is increasingly recognized as a critical factor influencing outcomes in chronic illness management, particularly in patients with end-stage renal disease (ESRD). The present study examines the psychological burden associated with long-term hemodialysis in patients with ESRD, focusing on emotional distress and maladaptive personality traits. Specifically, it explores group differences between hemodialysis patients and matched healthy controls in levels of stress, anxiety, depression, and psychopathological tendencies, including neuroticism, paranoia, and psychopathy-related traits, as well as exploratory associations with treatment duration. A purposive sample of 60 participants (30 patients undergoing chronic hemodialysis and 30 age- and sex-matched healthy controls) was assessed using validated psychometric instruments: The Hospital Anxiety and Depression Scale, the Pichot Neuroticism and Psychopathy Questionnaire, and a 23-item stress measurement questionnaire adapted to the dialysis context. Both descriptive and inferential statistical analyses were conducted, including independent-samples t-tests and effect size calculations (Cohen’s d). Compared to healthy controls, hemodialysis patients exhibited significantly higher levels of psychological distress across multiple domains. Large between-group effect sizes were observed for depression (Cohen’s d = 1.26) and perceived stress (d = 1.51), while moderate effects were identified for anxiety (d = 0.70), neuroticism (d = 0.58), and psychopathy-related traits (d = 0.82). Exploratory analyses indicated that patients with less than 10 years of dialysis experience reported significantly higher stress levels than those with longer treatment duration, whereas differences in anxiety, depression, and personality traits by dialysis duration were not statistically significant. These findings highlight the substantial emotional burden associated with long-term hemodialysis and underscore the importance of routine psychological screening and early psychosocial interventions to support adaptation, treatment adherence, and quality of life in nephrology care. Full article

Well-designed randomized controlled trials (RCTs) have demonstrated safe and effective use of oral antimicrobial therapy for bone and joint infections. Application of data for implementation into real-world practice, however, has inherent challenges. This retrospective cohort study compared real-world use of intravenous versus oral antimicrobial therapy in bone and joint infections within a large healthcare system comprising both academic and community medical centers. The primary outcome was the proportion of treatment failure. Key secondary outcomes included the proportion of patients with logistical failure and risk factors associated with treatment and logistical failure. Among 166 patients included, 136 (82%) and 30 (18%) received predominantly intravenous and oral antimicrobial therapy, respectively. Treatment failure occurred in (77/121) 64% versus (18/25) 72% of patients in the intravenous and oral antimicrobial groups (p = 0.491; OR, 1.38; 95% CI, 0.56–3.33). Logistical failure occurred in 29% versus 47% of patients in the intravenous and oral antimicrobial groups (p = 0.150; OR, 1.93; 95% CI 0.79–4.70). Risk factors for treatment failure included peripheral vascular disease (OR, 2.61; 95% CI 1.02–7.80) and higher Charlson Comorbidity Index scores (OR, 1.18; 95% CI 1.04–1.36). Similar to previously published RCTs, treatment failure appeared comparable between groups; however, oral antimicrobial therapy was overall underutilized. Full article

Background/Objectives: While the number and severity of comorbidities affecting survivors of craniopharyngioma (CP) are well documented, little is known about the perspectives of caregivers and survivors regarding treatment priorities. This study aimed to describe the views of caregivers and self-reported survivors on the comorbidities that most significantly impact CP survivors and to identify areas where new treatments are most needed. Methods: Completed surveys of 161 participants recruited in the hypothalamic–pituitary brain tumor patient registry were analyzed. Results: Participants represented 40% caregivers (mostly children) and 60% adult CP survivors, with notable differences in disease duration, age, CP onset, and living conditions. Seventeen health challenges were identified as most important by more than 50% of participants, including symptoms characteristic of hypothalamic dysfunction, neurological issues, and visual impairment. Notably, those differed from the most frequently experienced symptoms. No significant differences emerged between the two groups except for polydipsia, which had a greater impact on self-reported survivors. Most challenges primarily affected the survivors’ daily functioning; however, abnormal social behaviors equally impaired their ability to achieve long-term goals. Temperature dysregulation was the only symptom not deemed very or extremely important in prioritizing new treatment development. Both groups generally aligned on treatment priorities, though survivors placed a modest but significantly greater importance on fatigue and excessive daytime sleepiness, while caregivers placed a modest but significantly greater importance on obesity. Conclusions: Real-world survivor and caregiver perspectives on priority symptoms and treatments can inform care management, strengthen support strategies, and guide patient-focused drug development meaningful to CP survivors. Full article

Background: Despite improvements in life expectancy, people living with HIV (PWH) continue displaying immune activation and high rates of comorbid conditions. No comparative studies concerning activation markers exist between simplification strategies to either oral or long-acting (LA) dual ART. Methods: We prospectively collected plasma samples from PWH on successful ART, simplifying treatment from triple oral to either oral or LA dual ART based on integrase inhibitors. We measured changes in soluble CD14 (sCD14), soluble CD163 (sCD163), monocyte chemoattractant protein-1, and interleukin-6. Background measurements and markers of microbial translocation and gut integrity (I-FABP, LBP) were also collected. Results: From 2019 to 2023, 38 PWH were analyzed (mean age 52, 87% male, 21 years HIV diagnosis, CD4 730 cells/mm³, nadir CD4 317 cells/mm³, AIDS 13%). After 7.2 months, sCD14 trajectories differed according to regimen (+0.43 ng/mL, p = 0.033 for LA ART, −0.62 ng/mL, p < 0.001 for oral ART) but were not related to I-FABP or to LBP values. In case of CD4 nadir < 200 cc/mm³, AIDS, or very-low-level viremia, sCD163 values significantly increased when switching to oral but not to LA dual ART. Conclusion: We found different trends in immune activation markers and risk factors associated with PWH switching to either oral or LA ART, requiring larger studies. Full article

Background: Anorexia nervosa (AN) is a severe eating disorder occurring most frequently in adolescence, characterized by a high prevalence of psychiatric comorbidity. Emotional dysregulation (ED) refers to a transdiagnostic construct that often drives disordered eating behavior. The present study aimed to evaluate differences and similarities in the clinical presentation and response to treatment of young AN patients with high levels of ED (AN+ED) and with low levels of ED (AN−ED). Methods: A total of 40 female inpatients aged between 12 and 18 years were consecutively recruited and subdivided into two groups (AN+ED: n = 21; AN−ED: n = 19), based on the median of the subscale Affective Instability (AI) of the Reactivity, Intensity, Polarity and Stability questionnaire—youth version (RIPoSt-Y). At the recruitment (T0), and after 6 months (T1), the Body Mass Index (BMI) was calculated, and questionnaires and scales were administered to assess (a) the general functioning; (b) the severity of the eating disorder; and (c) the associated psychopathology. Results: At T0, an independent-samples t-test showed that the AN+ED group was characterized by a significantly greater impairment in clinical functioning and a greater severity of both the eating disorder and the associated psychopathology compared to the AN−ED group. At T1, the AN+ED group also showed significantly higher levels of cyclothymic, depressive, and anxious symptoms than the AN−ED group. Moreover, repeated-measures ANOVAs revealed a statistically marked improvement over time of the bulimic behaviors in the AN+ED group only. Conclusions: The present study underscored distinctive clinical features in AN patients with high and low levels of ED. Specifically, the AN+ED group was characterized by a most likely severe clinical phenotype that requires tailored intervention strategies. Full article

Background/Objectives: Patients with pre-existing heart failure (HF) represent a clinically vulnerable population with increased susceptibility to adverse outcomes during acute systemic illnesses, including coronavirus disease 2019 (COVID-19). Systemic inflammation is increasingly recognized as a central pathophysiological mechanism linking cardiovascular vulnerability with infection-related organ dysfunction. However, the prognostic role of inflammatory biomarkers in hospitalized COVID-19 patients with pre-existing HF remains incompletely defined. This study aimed to evaluate the association between inflammatory biomarkers and clinical outcomes in this high-risk population. Methods: This retrospective single-center cohort study included 395 consecutive adult patients hospitalized with confirmed COVID-19 between March 2020 and December 2024 at a tertiary referral center. Pre-existing HF was documented in 143 patients (36.2%). Inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin, and D-dimer, were measured at admission. The primary outcomes were development of sepsis and in-hospital mortality. Multivariable logistic regression models were constructed to identify independent predictors of adverse outcomes after adjustment for demographic characteristics, comorbidities, disease severity, and cardiac biomarkers. Results: Patients with pre-existing HF had significantly higher in-hospital mortality compared with those without HF (11.9% vs. 4.8%, p = 0.016) and showed a trend toward increased intensive care unit admission. HF patients exhibited higher admission IL-6 levels, indicating enhanced inflammatory activation. In univariable analysis, HF was associated with mortality (OR 2.67, 95% CI 1.22–5.83, p = 0.014). After multivariable adjustment, the association between HF and mortality was attenuated, whereas IL-6 remained an independent predictor of mortality (adjusted OR 1.38, 95% CI 1.04–1.82, p = 0.021). Elevated IL-6 and procalcitonin levels were also independently associated with sepsis development. Conclusions: Pre-existing heart failure identifies a population at increased risk of adverse outcomes in hospitalized COVID-19 patients, and this excess risk appears to be partly mediated by systemic inflammatory activation. Interleukin-6 emerged as a key biomarker linking cardiovascular vulnerability, immune dysregulation, and clinical deterioration. These findings support the potential role of inflammation-based risk stratification to improve prognostic assessment and guide personalized management in high-risk patients with underlying cardiovascular disease. Full article

Background: Non-cardiac comorbidities (NCCs) are highly prevalent among patients hospitalized for acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on their distribution across HF phenotypes and association with in-hospital outcomes remain limited. Methods: We prospectively enrolled adults hospitalized with acute HF at a tertiary centre in South Africa between February and November 2023. Ten NCCs were assessed and patients were categorized according to comorbidity burden. The primary outcomes were all-cause in-hospital mortality and length of stay. Multivariable regression and sensitivity analyses were performed to identify predictors of outcomes. Results: Of the 406 patients (mean age 54.9 ± 15.8 years; 51% women), HF with reduced ejection fraction (HFrEF) accounted for 63%, HF with mildly reduced ejection fraction (HFmrEF) for 15%, and HF with preserved ejection fraction (HFpEF) for 21%. The most common NCCs were diabetes (47%), chronic kidney disease (CKD) (46%), obesity (45%), and anaemia (33%). Two-thirds had ≥2 NCCs. The median hospital stay was 8 days (IQR: 5–12) and in-hospital mortality was 3.4% (p > 0.05 across NCC groups). Higher heart rate predicted longer hospitalization, while renin angiotensin system inhibitor (RASi) therapy was associated with shorter stay. Lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score (adjusted odds ratio [aOR] 1.009; 95% confidence interval [CI]: 1.003–1.015) and higher log-transformed NT-proBNP were independently associated with increased in-hospital mortality (aOR 1.85; 95% CI: 1.07–3.50; p = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. Conclusions: Non-cardiac comorbidities are common in acute HF in SSA, and functional status and clinical markers were the strongest predictors of length of stay and in-hospital mortality. Full article