Search Results (1,109)

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more complex models incorporating biomarkers (e.g., NT-proBNP, sST2), imaging, and artificial intelligence techniques. In acute HF, models like EHMRG and STRATIFY aid early triage, while in chronic HF, tools like SHFM and BCN Bio-HF support long-term management decisions. Despite their utility, most models are limited by poor generalizability, reliance on static inputs, lack of integration into electronic health records, and underuse in clinical practice. Novel approaches involving machine learning, multi-omics profiling, and remote monitoring hold promise for dynamic and individualized risk assessment. However, these innovations face challenges regarding interpretability, validation, and ethical implementation. For prognostic models to transition from theoretical promise to practical impact, they must be continuously updated, externally validated, and seamlessly embedded into clinical workflows. This review emphasizes the potential of prognostic models to transform HF care but cautions against uncritical adoption without robust evidence and practical integration. In the evolving landscape of HF management, prognostic models represent a hopeful avenue, provided their limitations are acknowledged and addressed through interdisciplinary collaboration and patient-centered innovation. Full article

Background: Peripancreatic collections (PPCs) are a frequent and severe complication of acute and chronic pancreatitis, as well as pancreatic surgery, often requiring interventions to treat and prevent infection, gastric obstruction, and other complications. Endoscopic ultrasound (EUS)-guided drainage has emerged as a minimally invasive alternative to surgical and percutaneous approaches, offering reduced morbidity and shorter recovery times. However, the effectiveness of EUS-guided drainage in post-surgical PPCs remains underexplored. Methods: This retrospective, single-center study evaluated the technical and clinical outcomes of EUS-guided drainage in patients with PPCs between October 2021 and December 2024. Patients were categorized as having post-pancreatitis or post-surgical PPCs. Technical success, clinical success, complications, recurrence rates, and the need for reintervention were assessed. Results: A total of 50 patients underwent EUS-guided drainage, including 42 (84%) with post-pancreatitis PPCs and 8 (16%) with post-surgical PPCs. The overall technical success rate was 100%, with clinical success achieved in 96% of cases. Lumen-apposing metal stents (LAMSs) were used in 84% of patients, including 7.1% as a dual-gate salvage strategy after the failure of double-pigtail drainage. The complication rate was 24%, with infection being the most common (16%). The recurrence rate was 25%, with no significant difference between post-pancreatitis and post-surgical cases. Patients with walled-off necrosis had a significantly higher reintervention rate (35%) than those with pseudocysts (18%; p = 0.042). Conclusions: EUS-guided drainage is a highly effective and safe intervention for PPCs, including complex post-surgical cases. The 100% technical success rate reinforces its reliability, even in anatomically altered post-surgical collections. While recurrence rates remain a consideration, EUS-guided drainage offers a minimally invasive alternative to surgery, with comparable outcomes in both post-pancreatitis and post-surgical patients. Future multi-center studies should focus on optimizing treatment strategies and reducing recurrence in high-risk populations. Full article

Aims/Background: Polypharmacy, or the concurrent intake of five or more medications, is a significant issue in clinical practice, particularly in multimorbid elderly individuals. Despite its importance for patient safety, medical education often lacks systematic training in recognising and managing polypharmacy within the framework of patient-centred care. We investigated the impact of a structured learning intervention introducing polypharmacy as a chronic condition, assessing whether it enhances medical students’ diagnostic competence, confidence, and interprofessional collaboration. Methods: A prospective cohort study was conducted with 50 final-year medical students who received a three-phase educational intervention. Phase 1 was interactive workshops on the principles of polypharmacy, its dangers, and diagnostic tools. Phase 2 involved simulated patient consultations and medication review exercises with pharmacists. Phase 3 involved reflection through debriefing sessions, reflective diaries, and standardised patient feedback. Student knowledge, confidence, and attitudes towards polypharmacy management were assessed using pre- and post-intervention questionnaires. Quantitative data were analysed through paired t-tests, and qualitative data were analysed thematically from reflective diaries. Results: Students demonstrated considerable improvement after the intervention in identifying symptoms of polypharmacy, suggesting deprescribing strategies, and working in multidisciplinary teams. Confidence in prioritising polypharmacy as a primary diagnostic problem increased from 32% to 86% (p < 0.01), and knowledge of diagnostic tools increased from 3.1 ± 0.6 to 4.7 ± 0.3 (p < 0.01). Standardised patients felt communication and patient-centredness had improved, with satisfaction scores increasing from 3.5 ± 0.8 to 4.8 ± 0.4 (p < 0.01). Reflective diaries indicated a shift towards more holistic thinking regarding medication burden. The small sample size limits the generalisability of the results. Conclusions: Teaching polypharmacy as a chronic condition in medical school enhances diagnostic competence, interprofessional teamwork, and patient safety. Education is a structured way of integrating the management of polypharmacy into routine clinical practice. This model provides valuable insights for designing medical curricula. Future research must assess the impact of such training on patient outcomes and clinical decision-making in the long term. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Background: Urinary tract trauma encompasses injuries to the kidneys, ureters, urinary bladder, and urethra and can result from both external and iatrogenic causes. We aimed to evaluate the epidemiology, clinical characteristics, and in-hospital outcomes of urinary tract trauma in Germany. Methods: We analyzed data from the GeRmAn Nationwide inpatient Data (GRAND) registry, provided by the Research Data Center of the Federal Bureau of Statistics, from 2005 to 2023. We included patients admitted to the hospital with kidney, ureteral, urinary bladder, or urethral trauma. We assessed baseline characteristics, perioperative outcomes, surgical interventions, in-hospital all-cause mortality, and trends. Results: We identified 239,657 patients with urinary tract trauma: 109,376 with kidney, 34,330 with ureteral, 57,886 with bladder, and 38,065 with urethral trauma. While the incidence of kidney trauma declined, the incidence of ureteral, bladder, and urethral trauma steadily increased over time. Kidney trauma was the most common trauma, affecting younger males (median age of 47 years), and was associated with in-hospital all-cause mortality of 2.4% and transfusion rates of 15%. Ureteral stenting was necessary in 9.3% and nephrectomy in 2.6% of all patients with kidney trauma. Moreover, ureteral, bladder, and urethral trauma predominantly affected older, multimorbid patients, leading to higher rates of transfusion (22–25%), intensive care unit admission (12–15%), and mortality (3.2–6.4%). Ureteral anastomosis was necessary in 14% of all ureteral injuries. Bladder repair was required in 53% of all patients with bladder injury, while 1% of these patients required cystectomy. Accordingly, urethral reconstruction was performed in 7.2% of all patients with urethral trauma. Conclusions: These findings highlight the evolving landscape of urinary tract trauma and underscore the need for tailored management strategies and preventive measures. Full article

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article

Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical data now demonstrate its ability to reduce cancer incidence, enhance immunotherapy outcomes, delay multimorbidity, and reverse biological age markers. Landmark trials such as UKPDS, CAMERA, and the ongoing TAME study illustrate its broad clinical impact on metabolic health, cardiovascular risk, and age-related disease trajectories. In oncology, trials such as MA.32 and METTEN evaluate its influence on progression-free survival and tumor response, highlighting its evolving role in cancer therapy. This review critically synthesizes the molecular underpinnings of metformin’s polypharmacology, examines results from pivotal clinical trials, and compares its effectiveness with emerging gerotherapeutics and senolytics. We explore future directions, including optimized dosing, biomarker-driven personalization, rational combination therapies, and regulatory pathways, to expand indications for aging and oncology. Metformin stands poised to play a pivotal role in precision strategies that target the shared roots of aging and cancer, offering scalable global benefits across health systems. Full article

Kidney transplant recipients face a substantial burden of premature mortality and morbidity, primarily due to persistent inflammation, cardiovascular risk, and nutritional deficiencies. Traditional nutritional interventions in this population have either focused on supplementing individual nutrients—often with limited efficacy—or required comprehensive dietary overhauls that compromise patient adherence. In this narrative review, we explore the rationale for dietary nut enrichment as a feasible, multi-nutrient strategy tailored to the needs of kidney transplant recipients. Nuts, including peanuts and tree nuts with no added salt, sugar, or oil, are rich in beneficial fats, proteins, vitamins, minerals, and bioactive compounds. We summarize the multiple post-transplant challenges—including obesity, sarcopenia, dyslipidemia, hypertension, immunological dysfunction, and chronic inflammation—and discuss how nut consumption may mitigate these issues through mechanisms involving improved micro-nutrient intake (e.g., magnesium, potassium, selenium), lipid profile modulation, endothelial function, immune support, and gut microbiota health. Additionally, we highlight the scarcity of randomized controlled trials in high-risk populations such as kidney transplant recipients and make the case for studying this group as a model for investigating the clinical efficacy of nuts as a nutritional intervention. We also consider practical aspects for future clinical trials, including the choice of study population, intervention design, duration, nut type, dosage, and primary outcome measures such as systemic inflammation. Finally, potential risks such as nut allergies and oxalate or mycotoxin exposure are addressed. Altogether, this review proposes dietary nut enrichment as a promising, simple, and sustainable multi-nutrient approach to support cardiometabolic and immune health in kidney transplant recipients, warranting formal investigation in clinical trials. Full article

Background/objective: Tailoring involves adapting research findings and evidence to suit specific contexts and audiences. This study examines how international stroke guidelines can be tailored to address gait issues after a stroke. Methods: A three-phase consensus method approach was used. A 10-member health experts panel extracted recommendations from three national clinical guidelines in the first phase. In the second phase, 362 physiotherapists completed an online questionnaire to assess the feasibility of adopting the extracted recommendations. In the third phase, a 15-physical therapist consensus workshop was convened to clarify factors that might affect the tailoring process of the extracted recommendations of gait disorder rehabilitation. Results: In phase one, 21 recommendations reached consensus. In the second phase, 362 stroke physiotherapists rated the applicability of these recommendations: 14 rated high, 7 rated low, and none were rejected. The third phase, a nominal group meeting (NGM), explored four themes related to tailoring. The first theme, “organizational factors”, includes elements such as clinical setting, culture, and regulations. The second theme, “individual clinician factors”, assesses aspects like clinical experience, expertise, abilities, knowledge, and attitudes toward tailoring. The third theme, “patient factors”, addresses issues related to multimorbidity, comorbidities, patient engagement, and shared decision-making. The final theme, “other factors”, examines the impact of research design on tailoring. Conclusions: Tailoring international clinical guidelines involves multiple factors. This situation brings home the importance of a systematic strategy for tailoring that incorporates various assessment criteria to enhance the use of clinical evidence. Future research should investigate additional implementation theories to enhance the translation of evidence into practice. Full article

Background: People with cystic fibrosis (pwCF) frequently suffer from chronic lung infections, with Pseudomonas aeruginosa being the predominant pathogen contributing to disease progression and morbidity. The increasing prevalence of multi-drug-resistant (MDR) P. aeruginosa has diminished treatment options. Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics due to their unique membrane-targeting mechanisms. OMN51, a novel bioengineered AMP derived from capitellacin, was evaluated for antimicrobial activity against P. aeruginosa in sputum samples from pwCF. This study aimed to compare the bactericidal effects of OMN51 with those of a range of conventional antibiotics known to have activity against P. aeruginosa clinical isolates derived from pwCF. Methods:P. aeruginosa clinical isolates were obtained from fifty-six unique sputum cultures of pwCF at a tertiary-university-affiliated hospital. Minimum inhibitory concentrations (MICs) of OMN51 and comparator antibiotics were determined using broth microdilution. Antimicrobial susceptibility was evaluated using the Kirby–Bauer disc diffusion method. Results: OMN51 demonstrated in vitro bactericidal activity across all P. aeruginosa isolates, including MDR strains. MIC values for OMN51 ranged from 4 to 16 µg/mL, with no observed resistance or cross-resistance. Comparative analysis revealed the superior efficacy of OMN51 compared with conventional antibiotics. Conclusions: OMN51 exhibits robust in vitro activity against MDR P. aeruginosa, supporting its candidacy as a therapeutic agent for MDR P. aeruginosa- associated infections. Further studies are warranted to assess pharmacokinetics and in vivo safety and efficacy. OMN51 represents a first-in-class, membrane-targeting therapeutic showing promise against MDR P. aeruginosa. Full article

Background: Apathy predicts functional and cognitive decline in community-dwelling older adults. However, the behavioral correlates of apathy, which could promote cognitive decline have not been described. Our objective was to investigate the associations of apathy with leisure and social engagement. Methods: N = 538 older adults enrolled in the Central Control of Mobility in Aging study. We used the GDS3A, a 3-item subscale of the Geriatric Depression Scale, to define apathy and the frequency of participation in cognitive, physical, and social leisure activities. Linear regression models were conducted to assess the association between apathy and its behavioral correlates: social engagement and leisure activity participation. Covariates included age, gender, education level, multimorbidity, and dysphoria. Results: Apathy was present in 29.7% of participants and was significantly associated with less frequent participation in physical activity days per week (−1.688. p = 0.003) but not cognitive (−1.094, p = 0.252) or social (−0.654, p = 0.103) leisure activities. Apathy was also associated with a decreased social behavior composite score (−0.055, p < 0.001), Social Network Index (−0.478, p = 0.003), and Medical Outcomes Study Social Support scores (−0.26, p = 0.001). Conclusions: Our findings suggest that apathy presents with reduced participation in physical leisure activities and reduced social engagement, which may provide a way for clinicians and caregivers to identify apathy in the future. Full article

Aging is a multifaceted biological process characterized by a progressive decline in cellular function and physiological resilience, increasing the risk of multiple chronic conditions. Chronic lung diseases frequently manifest within the aging population and are closely intertwined with systemic dysfunctions across cardiovascular, musculoskeletal, and neurological systems. In this review, we explore the biological mechanisms linking aging, multiple chronic conditions patterns, and chronic lung disease, with a particular focus on inflammaging and cellular aging. We also highlight shared pathological pathways such as oxidative stress, mitochondrial dysfunction, and the dysregulation of repair processes that underlie both natural aging and the accelerated aging seen in chronic lung disease. Additionally, we discuss the systemic impact of multiple chronic conditions on patient outcomes, including increased frailty, diminished physical capacity, cognitive impairment, and elevated mortality risk. This review advocates for a comprehensive, patient-centered approach that combines early detection, personalized pharmacological therapies targeting inflammatory and senescent pathways, and non-pharmacological interventions such as pulmonary rehabilitation, exercise, and dietary optimization. Emerging therapeutics, including senolytics and anti-inflammatory agents, present promising avenues for mitigating age-related lung decline and managing multiple chronic conditions. Full article

Heart failure (HF) is a global health burden characterized by high morbidity and mortality, necessitating advancements in diagnostic and therapeutic approaches. Molecular diagnostics, encompassing genomics, transcriptomics, proteomics, metabolomics, and epigenetics, offer unprecedented insights into HF pathogenesis, aiding early diagnosis, risk stratification, and personalized management. This state-of-the-art review critically examines recent developments in molecular diagnostics in HF, evaluates their translational potential, and highlights key challenges in clinical implementation. Emerging tools such as liquid biopsy, multi-omics integration, and artificial intelligence (AI)-driven platforms are explored. We propose strategies to enhance clinical translation, equity in access, and utility in guiding treatment, thereby advancing precision cardiovascular medicine Full article

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality, prompting significant interest in individualized prevention and treatment strategies. This review synthesizes recent advances in genomic and precision medicine approaches relevant to ASCVD, with a focus on genetic risk scores, lipid metabolism genes, and emerging gene editing techniques. A structured literature search was conducted across PubMed, Scopus, and Web of Science databases to identify key publications from the last decade addressing genomic mechanisms, therapeutic targets, and computational tools in ASCVD. Notable findings include the identification of causal genetic variants such as PCSK9 and LDLR, the development of polygenic risk scores for early prediction, and the use of deep learning algorithms for integrative multi-omics analysis. In addition, we highlight current and future therapeutic applications including PCSK9 inhibitors, RNA-based therapies, and CRISPR-based genome editing. Collectively, these advances underscore the promise of precision medicine in tailoring ASCVD prevention and treatment to individual genetic and molecular profiles. Full article