Search Results (39)

Background/Objectives: The corneal endothelium maintains corneal transparency through its barrier function and active pumping mechanism that regulates stromal hydration. Limited regenerative capacity makes these cells vulnerable to progressive cell loss. Although local ocular factors are well known, recent data suggest that numerous systemic diseases may contribute to endothelial dysfunction and reduce endothelial reserve before the onset of clinically apparent corneal pathology. The purpose of this narrative review is to synthesize current evidence on the impact of systemic diseases on corneal endothelial health and to highlight the underlying mechanisms and clinical implications. Methods: A narrative literature review was conducted using the PubMed, MEDLINE, and Google Scholar databases for articles published between January 2000 and December 2025. Observational studies, case series, and review articles that evaluated structural or functional changes in the corneal endothelium in association with systemic diseases were included. Results: Reviewed literature shows that several categories of systemic diseases are associated with signs of corneal endothelial stress. These changes include decreased endothelial cell density, increased cell size variability, reduced hexagonality, and, in some cases, increased central corneal thickness. Metabolic, cardiovascular, renal, autoimmune, and hypoxic conditions, as well as extracellular matrix disorders and aging, show consistent associations with these changes. Conclusions: Systemic diseases can compromise corneal endothelial integrity and reduce functional reserve even in the absence of clinically evident corneal pathology. Recognition of these associations underscores the importance of evaluating the patient’s systemic context, including a detailed medical history and corneal endothelial analysis, particularly before intraocular surgery. Full article

The transjugular intrahepatic portosystemic shunt (TIPS) is a cornerstone intervention for complications of portal hypertension, including variceal bleeding and refractory ascites. As the population with cirrhosis ages, clinicians increasingly face the question of whether and how to perform TIPS safely in older adults. We reviewed observational cohorts, registry analyses, and systematic reviews/meta-analyses. Existing evidence does not support chronological age as an absolute contraindication; however, multiple studies suggest that advanced age is associated with higher rates of post-TIPS hepatic encephalopathy (HE), early mortality, and readmissions. These findings underscore the need to shift from a binary “eligible vs. ineligible” paradigm to a structured, actionable framework that addresses modifiable risks and anticipates age-related vulnerabilities. Recent clinical practice guidance emphasizes comprehensive pre-TIPS assessment and vigilant post-procedure care, with specific attention to HE risk factors (e.g., prior HE, hyponatremia, renal dysfunction, sarcopenia) and cardiopulmonary reserve. In this narrative review, we propose an elderly-focused clinical pathway built around a four-domain assessment (Liver–Brain–Body–Heart/Kidney) and a traffic-light risk tiering system to guide patient selection, procedural strategy, follow-up scheduling, and triggered management of HE, cardiac decompensation, and renal dysfunction. This pathway aims to preserve the benefits of portal decompression while reducing preventable complications and improving outcomes that are meaningful to older patients, including functional status and quality of life. This narrative review emphasizes that outcomes after TIPS in older adults are determined not by chronological age alone but by multidomain physiological reserve. The proposed pathway informs patient selection, procedural planning, and early post-discharge monitoring in older adults. Full article

The aging of the population and the increasing prevalence of multimorbidity contribute to the widespread use of polypharmacotherapy, which in turn elevates the risk of adverse drug reactions and clinically significant drug–drug interactions. One of the key yet frequently underestimated issues in clinical practice is the prescribing cascade, which occurs when an adverse drug reaction is misinterpreted as a new medical condition, leading to the initiation of an additional medication. This phenomenon is particularly relevant in the older population, in whom altered pharmacokinetics and pharmacodynamics, together with reduced organ reserve, increase susceptibility to adverse drug events, including nephrotoxicity (renal impairment is used throughout the review as a clinically relevant example of organ-specific harm resulting from prescribing cascades, rather than as the sole focus of the analysis). This article discusses the mechanisms and clinical consequences of the prescribing cascade—with particular emphasis on renal function deterioration—as well as strategies for its prevention in the geriatric population. Analysis of the literature indicates that prescribing cascades remain insufficiently recognized in clinical practice, despite the availability of pharmacotherapy assessment tools such as The American Geriatrics Society (AGS) Beers Criteria and the STOPP/START criteria. Documented prescribing cascades have been shown to contribute to deterioration in health status and quality of life, an increased frequency of hospitalizations, and a greater burden on healthcare systems. Particularly concerning are cascades involving cardiovascular, neurological, and analgesic medications, which may induce or exacerbate renal injury, ultimately leading to chronic kidney disease and organ failure. Prescribing cascades represent a significant yet frequently underestimated threat to the efficacy and safety of pharmacotherapy in older adults. Their consequences may extend beyond reduced quality of life and increased treatment costs to include serious complications such as the development of renal failure. Enhancing clinicians’ awareness, conducting systematic medication reviews, and employing validated assessment tools are essential for the identification and prevention of prescribing cascades, thereby reducing the risk of renal injury and improving clinical outcomes. Full article

Background/Objectives: Renal cell carcinoma (RCC) care has been reshaped by immune checkpoint inhibitors (ICIs), now used across adjuvant and metastatic settings as PD-1/PD-L1 blockade alone, combined with anti-CTLA-4 agents, or in combination with vascular endothelial growth factor (VEGF)-targeting tyrosine kinase inhibitors (TKIs). As survival improves and systemic therapy courses extend, survivorship priorities—including fertility preservation, reproductive endocrine health, contraception, and pregnancy counselling—become increasingly relevant, even though RCC-specific oncofertility evidence remains sparse. This review examines the biological rationale and clinical considerations underpinning reproductive counselling for women of reproductive age exposed to ICIs (alone or with TKIs) in RCC. Methods: A narrative review was conducted in accordance with the SANRA framework, integrating targeted PubMed/MEDLINE searches up to 20 February 2026 and consultation of regulatory product labels to synthesize mechanistic, clinical, and safety data relevant to fertility, endocrine function, contraception, pregnancy, and breastfeeding in RCC. Results: We delineate the contemporary RCC treatment landscape to identify feasible timepoints for fertility preservation discussions and propose a pragmatic, implementation-oriented counselling framework that distinguishes evidence-secure recommendations (pregnancy avoidance during therapy, endocrine monitoring, agent-specific washout) from extrapolative domains (long-term ovarian reserve effects and post-ICI periconception safety beyond label intervals). Conclusions: By integrating a ‘multi-hit’ biological rationale, treatment context, and available human data, this review highlights RCC-specific research priorities while supporting transparent, evidence-aligned, and multidisciplinary counselling for both fertility preservation and pregnancy safety in the ICI era. Full article

Background: Renal function deterioration during hospitalization for acute heart failure (AHF) is common and is traditionally classified as acute kidney injury (AKI) or worsening renal function (WRF) based on changes in serum creatinine (Cr). However, Cr-based definitions may inadequately reflect the complex cardiorenal interactions occurring in AHF. Purpose: This narrative review summarizes and compares definitions of AKI and WRF used in AHF, evaluates their prognostic significance, and explores whether renal function deterioration should be interpreted as a marker of cardiorenal disease severity rather than isolated kidney injury. Methods: A narrative review of randomized trials, observational studies, post hoc analyses, and meta-analyses was conducted, focusing on Cr-based and nephrology-derived AKI definitions (RIFLE, AKIN, KDIGO), timing and baseline selection, congestion status, and the role of biomarkers and imaging in clinical interpretation. Results: The most widely used definition of WRF is an absolute increase in serum Cr ≥ 0.3 mg/dL. Multiple studies demonstrate that such changes frequently occur during effective decongestion and are not independently associated with adverse outcomes in the absence of residual congestion. In contrast, persistent congestion, impaired diuretic response, reduced renal reserve, and advanced cardiorenal comorbidity consistently predict worse prognosis. Nephrology-derived AKI definitions identify higher-risk patients but incompletely account for the hemodynamic and therapeutic context of AHF. Conclusions: In AHF, AKI and WRF often act as markers of underlying cardiorenal disease severity rather than direct indicators of irreversible kidney injury. Interpretation of renal function deterioration should be contextual, integrating congestion status, perfusion, renal reserve, and dynamic response to therapy. Achieving effective and complete decongestion remains the primary therapeutic objective in AHF, even in the presence of transient Cr increases. Full article

Background: Ageing profoundly alters endocrine regulation and nutrient metabolism, predisposing older adults to thyroid dysfunction. Iodine, an essential micronutrient, lies at the center of this vulnerability due to its narrow physiological range and multiple interactions with nutrition, medications, renal function, and, presumably, gut microbiota. Objective: This narrative review integrates evidence on how ageing modifies iodine–thyroid homeostasis, emphasizing the roles of dietary intake, pharmacologic exposures, microbiota composition, and age-related metabolic alterations that influence iodine handling and thyroid hormone economy. Main Findings: Physiological ageing reduces renal iodine clearance, thyroidal reserve, and peripheral hormone conversion, while chronic inflammation and multimorbidity increase susceptibility to both iodine deficiency and excess. Polypharmacy, including amiodarone, lithium, and proton pump inhibitors, further destabilizes thyroid function. Age-related dysbiosis may impair micronutrient absorption and immune tolerance, linking gut ecology to thyroid autoimmunity. The gut microbiota may influence thyroid function through immune and metabolic pathways, although current evidence in older adults remains limited. Together, these factors shift the balance between iodine intake and utilization, heightening the risk of subclinical or overt hypothyroidism in older adults. Conclusions: Overall, variations in iodine intake emerge as one of the main determinants of thyroid dysfunction in ageing with nutritional, pharmacologic, and other modifiers primarily influencing iodine-related thyroid vulnerability. The adoption of age-adjusted thyroid reference ranges and preventive monitoring can reduce overtreatment and improve metabolic resilience in later life. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

Background: Orthotopic heart transplantation (OHT) remains the gold standard for end-stage heart failure, yet individualized risk assessment for postoperative mortality remains challenging. We aimed to develop and interpret random forest-based models for predicting 30-day and 1-year mortality and to examine whether the key predictors differ between the 30-day and 1-year models. Methods: We analyzed 581 patients who underwent OHT between 2012 and 2024. The 30-day and 1-year mortality rates were 9.9% and 17.6%, respectively. Eighty-seven preoperative and forty-eight postoperative variables were considered as input features for model development. Random forest models were trained and validated using five-fold cross-validation, and explainability was assessed using SHapley Additive exPlanations (SHAP). Results: Using preoperative features only, the random forest models achieved AUCs of 0.62 (95% CI, 0.48–0.75) for 30-day and 0.67 (95% CI, 0.56–0.78) for 1-year mortality. SHAP analysis revealed that early mortality predictions were primarily driven by features reflecting acute physiological stress—hepatic dysfunction, inflammation, and hemodynamic instability—whereas long-term predictions were increasingly influenced by renal function, metabolic reserve, and frailty. Incorporating postoperative features improved performance (AUC 0.98 [95% CI, 0.97–0.99] and 0.86 [95% CI, 0.80–0.92], respectively), with model predictions dominated by the severity and persistence of organ dysfunction: short-term risk driven by hepatic injury, hemodynamic compromise, and critical illness, and long-term risk by sustained hepatic and renal impairment, metabolic resilience, and duration of circulatory support. Conclusions: Random forest models integrating preoperative and immediate postoperative data could predict short- and mid-term mortality after OHT. SHAP analysis demonstrated temporal shifts in the most important predictors, supporting the role of dynamic, data-driven risk assessment in transplant care. Full article

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m²), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO₂ < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates. Full article

Acute kidney injury (AKI) occurs commonly in hospitalized patients, especially patients in intensive care units (ICUs). Medications are among the major causative factors of AKI. This narrative review addressed and updated different aspects of anti-infective-associated AKI, including amphotericin B, cidofovir, foscarnet, polymyxins, vancomycin, and aminoglycosides. There is no standard definition or operational criteria to describe anti-infective-associated AKI. Characteristically, it usually occurs during the first two weeks of treatment and is typically dose dependent. Functional resolution occurs, but kidney injury can affect renal functional reserve and increase susceptibility to future AKI events. A variety of pathophysiological mechanisms impacting glomerular, tubular, and interstitial components of the kidney are usually responsible for the development of AKI from anti-infective medications. Oxidative stress and inflammation play a pivotal role in the pathogenesis of antibiotic-related AKI. Numerous patient-related, medication-related, and co-administered-related scenarios have been demonstrated as risk factors for anti-infective-induced AKI. Apart from traditional indexes of kidney function (serum creatinine and urine output), novel biomarkers of kidney function (e.g., serum cystatin C) and damage (e.g., urinary kidney-injury molecule-1 and neutrophil gelatinase-associated lipocalin) have been noticed in recent clinical studies with promising findings. The efficiency of preventive strategies against anti-infective-associated AKI in most cases appears to be variable, relative, and modest. Close and regular monitoring of kidney function parameters is crucial during treatment with nephrotoxic antibiotics. Currently, there is no definitive treatment modalities for the management of AKI with anti-infectives. Therefore, supportive care is the mainstay of treatment. Full article

Background: Sarcopenia and metabolic deterioration are major health concerns in adults aged ≥ 75 years with type 2 diabetes (T2DM), a population characterized by anabolic resistance, reduced dietary intake, and limited renal reserve. Optimizing protein nutrition may support muscle maintenance in this high-risk group, but clinical evidence for individualized high-protein guidance in the oldest-old population remains limited. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in adults aged ≥ 75 years with T2DM and whether serum amino acid (AA) and hormonal profiles reflect these changes. Methods: In this 18-month, single-arm, prospective intervention study, 44 community-dwelling adults aged ≥ 75 years with T2DM received individualized, dietitian-led nutritional guidance targeting a protein intake of approximately 1.4 g/kg ideal body weight (IBW)/day. Assessments at baseline and every 6 months included body composition, muscle strength, renal function, and fasting serum amino acid and hormonal profiles. Longitudinal changes were analyzed using paired t-tests and linear mixed-effects models. This trial was registered in the UMIN Clinical Trials Registry (UMIN000044687). Results: Skeletal muscle index and grip strength showed significant improvements at specific time points during follow-up (both p < 0.05), while gait speed improved at 6 months. Renal function remained clinically stable (eGFRcreat slope: +0.18 mL/min/1.73 m²/year; eGFRcys slope: −2.97 mL/min/1.73 m²/year), with no significant increase in CKD stage. Changes in glucagon correlated positively and C-peptide negatively with changes in skeletal muscle index, whereas glucagon was inversely associated with grip strength. Serum fibroblast growth factor 21 (FGF21) levels decreased over time, suggesting metabolic adaptation to the intervention. Conclusions: Individualized high-protein nutritional guidance for 18 months improved sarcopenia-related parameters, including skeletal muscle index and grip strength, without clinically significant deterioration of renal function in adults aged ≥ 75 years with T2DM. These findings support the feasibility and safety of protein-focused dietary counseling as a strategy to preserve muscle health in advanced age. Full article

Malnutrition afflicts millions of the world’s children and predisposes to death from diarrhea and infectious diseases. Children with severe acute malnutrition (SAM) are at highest risk. Our review of the endocrinology and metabolomics of SAM implicates critical roles for white adipose tissue and its regulatory hormones and growth factors in the adaptation to nutritional deprivation and the restoration of metabolic homeostasis: white adipose provides substrates and energy for hepatic glucose production and cardiopulmonary and central nervous system function, and products of fat metabolism inhibit muscle glucose uptake and utilization and spare muscle protein. Collectively, these effects maintain glucose availability for the brain, red blood cells, and renal medulla and conserve muscle mass. White adipose tissue also secretes leptin, which facilitates the immune response and may protect against mortality from infection. Euglycemia and survival in SAM are thereby prioritized over linear growth, which is suppressed owing to inhibition of insulin-like growth factor 1 production and action. Diversion of energy from growth serves to maintain essential bodily functions in critically ill malnourished children, who have limited energy reserves. Thus, short-term reductions in growth rate have adaptive benefits in SAM. Under favorable conditions, clinical and metabolic recovery are accompanied by catch-up growth, which can mitigate, and in many cases reverse, the stunting of growth in childhood. Nevertheless, clinical recovery can be complicated by preferential accrual of central fat and a relative deficiency of lean/skeletal mass, with potential long-term complications including insulin resistance, glucose intolerance, and metabolic syndrome. Full article

Cardiogenic shock (CS) in the setting of severe aortic stenosis (AS) presents a critical and high-risk scenario with limited therapeutic options and poor prognosis. Transcatheter aortic valve implantation (TAVI), initially reserved for inoperable or high-risk surgical candidates, is increasingly being considered in patients with CS due to improvements in device technology, operator experience, and supportive care. This review synthesizes current evidence from large registries, observational studies, and meta-analyses that support the feasibility, safety, and potential survival benefit of urgent or emergent TAVI in selected CS patients. Procedural success is high, and early intervention appears to confer improved short-term and mid-term outcomes compared to balloon aortic valvuloplasty or medical therapy alone. Critical factors influencing prognosis include lactate levels, left ventricular ejection fraction, renal function, and timing of intervention. The absence of formal guidelines, logistical constraints, and ethical concerns complicate decision-making in this unstable population. A multidisciplinary Heart Team/Shock Team approach is essential to identify appropriate candidates, manage procedural risk, and guide post-intervention care. Further studies and the development of TAVI-specific risk models in CS are anticipated to refine patient selection and therapeutic strategies. TAVI may represent a transformative option for stabilizing hemodynamics and improving outcomes in this otherwise high-mortality group. Full article

Background/Objectives: The course of treatment for renal artery stenosis following renal transplantation depends on the severity of the condition. Mild cases are typically managed medically, while more significant stenosis with flow limitation and graft dysfunction requires percutaneous intervention. Surgical treatment is generally reserved as a last resort. This study aimed to evaluate the outcomes of interventional radiology in managing renal artery stenosis at our transplant center. Methods: The electronic medical records of patients who underwent renal transplantation at our center between January 2020 and December 2024 were reviewed to identify cases of renal artery stenosis and their subsequent management through interventional radiology. Sociodemographic and clinical data were collected for both recipients and donors. Data analysis was performed using SPSS version 26. Results: Out of the total 368 patients who received renal allograft at our center from January 2020 to December 2024, 25 patients were confirmed with duplex ultrasound to have renal artery stenosis. The majority of affected patients were African American, had Class I Obesity and presented with cardiovascular co-morbidities. The mean time from transplant to the diagnosis of RAS was 4.25 (SD ± 3.81) months. The mean serum creatinine level at presentation was 2.54 (SD ± 1.21 mg/dL). All 25 patients underwent digital subtraction angiography, and 24 patients were confirmed to have renal artery stenosis requiring further intervention. The creatinine levels at one week, three months and one year post-intervention were 2.12 (SD ± 1.00), 1.83 (SD ± 0.63) and 2.15 (SD ± 1.68) mg/dL, respectively. Conclusions: Percutaneous interventional treatment for renal artery stenosis is associated with improvements in hemodynamic parameters and the stabilization of allograft function. Follow-up is needed to monitor for the potential occurrence of restenosis. Full article

Subclinical chronic kidney disease (sCKD) predisposes one to acute kidney injury (AKI) and chronic kidney disease (CKD). Reduced kidney functional reserve (KFR) detects sCKD in preclinical studies and predicts AKI after cardiac surgery. We evaluated renal protection in a rat model of kidney injury where ischaemia–reperfusion injury (IRI) was induced after sCKD. Dual treatment boosting nicotinamide adenine dinucleotide (NAD) by nicotinamide riboside (NR) combined with the mitochondria-targeted antioxidant SkQR1 protected the KFR and reduced structural kidney damage, including markers of vascular integrity and the relative blood volume (rBV). The dual treatment upregulated Sirt1 and Nrf2, increased the nuclear localisation of the mitochondrial biogenesis regulator PGC-1α and the mitochondrial protein marker COX4, and upregulated the antioxidant gene NOQ1. These observations suggest mitochondrial protection and modulation of the cellular redox state provided long-term structural and functional protection against kidney injury superimposed on background sCKD. Full article