Citations

Pediatric heart failure is a heterogeneous, high-risk clinical syndrome that differs fundamentally from adult heart failure in its etiologies, pathophysiology, and therapeutic responses. Although its absolute prevalence is lower, children experience disproportionate morbidity and mortality, with up to 40% of patients with symptomatic cardiomyopathy progressing to death or transplantation within 2 years of diagnosis. Congenital heart disease, cardiomyopathies, and genetic or metabolic disorders dominate the etiologic spectrum, while developmental differences in myocardial signaling, neurohormonal activation, and ventricular remodeling limit direct extrapolation of adult guideline-directed medical therapy. Evidence supporting pharmacologic treatment remains limited, and most therapies are symptom-modifying rather than outcome-modifying, particularly in single-ventricle physiology. Advances in mechanical circulatory support and heart transplantation have substantially improved survival, yet pose unique anatomic, physiological, and ethical challenges in children. This review synthesizes contemporary evidence across medical, device-based, and transplant therapies, highlights lesion- and age-specific considerations, and identifies critical research gaps needed to advance outcomes in pediatric heart failure.

Hypertension remains the leading modifiable risk factor for cardiovascular morbidity and mortality worldwide, yet blood pressure control rates remain suboptimal despite the availability of effective therapies. Contemporary guidelines increasingly recommend early use of combination therapy, recognizing that most patients require multiple agents to achieve target blood pressure. Widaplik, a recently Food and Drug Administration-approved fixed-dose, single-pill triple combination of telmisartan, amlodipine, and indapamide, represents the first triple therapy approved for initial treatment of hypertension in adults likely to need multidrug therapy. This review summarizes the pharmacologic rationale for low-dose triple therapy, highlighting complementary mechanisms targeting the renin-angiotensin-aldosterone system, vascular resistance, and sodium retention. We examine evidence from pivotal phase 3 trials demonstrating rapid, sustained blood pressure reductions, higher control rates compared with dual therapy, and favorable tolerability. We also discuss safety considerations, practical limitations, and gaps in evidence, including long-term cardiovascular outcomes. Widaplik represents a paradigm shift toward simplified, early combination therapy aimed at improving hypertension control and reducing cardiovascular risk.

Coronary microvascular dysfunction (CMD) is increasingly recognized as a central mechanism underlying myocardial ischemia, heart failure with preserved ejection fraction, and adverse cardiovascular outcomes in patients with and without obstructive coronary artery disease. The coronary microcirculation plays a critical role in regulating myocardial perfusion through tightly coordinated myogenic, metabolic, and endothelial pathways. Disruption of these mechanisms results in impaired vasodilatory capacity, abnormal coronary flow reserve, and microvascular ischemia. This review summarizes the anatomy and physiology of coronary microcirculation and examines the pathophysiologic mechanisms driving CMD, including endothelial dysfunction, structural remodeling, inflammation, and neurohormonal dysregulation. Contemporary diagnostic strategies are reviewed, with emphasis on invasive coronary function testing and advanced noninvasive imaging modalities such as positron emission tomography and cardiac magnetic resonance imaging. The clinical implications of CMD across diverse disease states, including ischemia with nonobstructive coronary arteries, heart failure, and cardiomyopathies, are discussed. Finally, current therapeutic approaches, prognostic considerations, and emerging research directions aimed at improving diagnosis and targeted treatment of CMD are highlighted.

Coronary artery spasm (CAS) is a dynamic vasomotor disorder characterized by transient, intense constriction of epicardial coronary arteries, leading to myocardial ischemia in patients with and without obstructive coronary artery disease. CAS plays a central role in vasospastic angina, ischemia with nonobstructive coronary arteries and myocardial infarction with nonobstructive coronary arteries, malignant arrhythmias, and sudden cardiac death. Its pathophysiology is multifactorial, involving endothelial dysfunction, vascular smooth muscle hyperreactivity, inflammation, oxidative stress, autonomic imbalance, and genetic susceptibility, with notable ethnic and sex-related differences. Diagnosis relies on integration of clinical features, electrocardiographic changes, and invasive coronary provocation testing using acetylcholine or ergonovine, supported by advanced imaging and functional assessment when microvascular involvement is suspected. Management is centered on calcium channel blockers and nitrates, aggressive risk factor modification, particularly smoking cessation, and individualized strategies for refractory or high-risk patients. Improved recognition and standardized diagnostic pathways are essential to optimize outcomes and reduce life-threatening complications associated with CAS.

Shock is a life-threatening state of circulatory failure characterized by inadequate tissue oxygen delivery and cellular hypoxia. Lactate has emerged as a central biomarker in the diagnosis, risk stratification, and management of shock, yet its interpretation is complex and context dependent. Although traditionally viewed as a marker of anaerobic metabolism and tissue hypoperfusion, hyperlactatemia in distributive shock, particularly sepsis, frequently reflects multifactorial mechanisms, including increased aerobic glycolysis, adrenergic stimulation, mitochondrial dysfunction, and impaired hepatic clearance. This review examines the pathophysiology and classification of shock, the biochemical basis of lactate production and clearance, and the prognostic significance of both static lactate levels and lactate kinetics. We synthesize evidence supporting lactate as a robust prognostic marker while highlighting limitations of lactate-targeted resuscitation strategies. Emerging data favor multimodal approaches integrating lactate trends with complementary perfusion markers such as capillary refill time and central venous oxygen saturation. Lactate should be interpreted as one component of a comprehensive physiological assessment rather than an isolated therapeutic target.

Background/Objective: Diabetic nephropathy (DN), a key microvascular complication of type 2 diabetes (T2DM), drives significant morbidity, mortality, and healthcare costs. Vitamin D deficiency has been linked to renal dysfunction, but its role in DN remains unclear. This study assessed the association between vitamin D status and DN versus T2DM without nephropathy. Methods: This cross-sectional hospital-based study included 399 participants (299 DN, 100 T2DM without nephropathy) at a tertiary endocrine clinic. Demographic, clinical, and biochemical data, including serum 25(OH)D, were collected. Chi-square and Mann–Whitney compared categorical and continuous variables, respectively, and multinomial logistic regression assessed the association between vitamin D status and DN (p < 0.05). Results: Patients with DN were older (58.2 ± 7.95 vs. 51.4 ± 9.94 years, p < 0.001), had more advanced CKD (stages 2–3b: 84.6% vs. 20.0%, p < 0.001), and higher albuminuria (moderate: 80.3% vs. 19.0%; severe: 18.4% vs. 0%, p < 0.001). They also showed poorer glycemic control, elevated urea and creatinine, lower serum albumin, dyslipidemia, elevated liver enzymes, and higher uric acid (all p < 0.05). Vitamin D deficiency was more prevalent in DN (37.7% vs. 8.0%, p < 0.001). Unadjusted multinomial regression indicated that T2DM patients without nephropathy had a 91% lower risk of vitamin D deficiency (RRR 0.09; 95% CI 0.04–0.19, p < 0.001) and an 87% lower risk of insufficiency (RRR 0.13; 95% CI 0.05–0.26, p < 0.001) compared with DN patients. After adjusting for age, HbA1c, creatinine, duration of diabetes and eGFR, the reduced risk of deficiency remained significant (RRR 0.04; 95% CI 0.01–0.16, p < 0.001), while the association with insufficiency was no longer significant (p = 0.310). Conclusions: This study shows a significant association between vitamin D deficiency and diabetic nephropathy, though its cross-sectional design precludes causal inference. Reverse causality and residual confounding cannot be excluded. Patients with DN had poorer glycemic control, dyslipidemia, and renal function, along with more frequent vitamin D deficiency. Routine vitamin D monitoring may support early detection and risk stratification in T2DM.

Background: Inflammatory bowel disease (IBD) is associated with systemic inflammation and potential cardiovascular complications. This meta-analysis evaluates long-term cardiovascular risks in IBD. Methods: Electronic databases were searched for studies examining cardiovascular, cerebrovascular, and thromboembolic risks in IBD. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Fifty-three studies comprising 1,406,773 patients were analyzed. IBD was linked to increased risk of ischemic heart disease (aHR 1.25; p = 0.001) myocardial infarction (aHR 1.25; p = 0.01), acute coronary syndrome (aHR 1.43; p < 0.00001), heart failure (aHR 1.24; p < 0.00001), atrial fibrillation (aHR 1.20; p < 0.00001), and stroke (aHR 1.13; p < 0.00001). Elevated risks were also observed for peripheral arterial disease (aHR 1.41; p < 0.00001), diabetes mellitus (aHR 1.40; p < 0.00001), venous thromboembolism (aHR 1.98; p < 0.00001), deep vein thrombosis (aHR 2.85; p = 0.0004), and pulmonary embolism (aHR 1.98; p = 0.03). Importantly, IBD was associated with increased cardiovascular (aHR 1.14; p = 0.03) and all-cause mortality (aHR 1.53; p < 0.00001). Conclusions: IBD patients face higher risk for adverse cardiovascular outcomes, thromboembolic disease, and mortality, necessitating early cardiovascular risk assessment and targeted interventions in this population.

Background: The use of spinal cord stimulation (SCS) for managing severe refractory chronic pain has expanded considerably due to positive statistical evidence regarding its use; however, the statistical robustness of the underlying randomized controlled trials (RCTs) requires further scrutiny. One such tool that can be used for this purpose is the fragility index, which quantifies how many individual outcome events must be altered for an outcome to lose statistical significance. Thus the index can be used quantitatively to assess the stability and robustness of an RCT’s conclusions, with higher values indicating increased trial stability. This study assesses the fragility of pain outcomes across RCTs investigating SCS for chronic pain to better understand the quality and robustness of evidence. Methods: A systematic search was conducted for RCTs assessing SCS for any chronic pain indication. The primary outcome was an evaluation of the trial-specific fragility index for the prespecified pain primary outcomes of RCTs. Secondary outcomes included an evaluation of fragility for (1) specified indications for SCS therapy, (2) reported pain outcomes appearing in three or more RCTs, (3) the presence/absence of a conflict of interest, and (4) comparisons of SCS to conservative management or different SCS waveform modalities. Results: A total of 30 RCTs were included. The median (interquartile range [IQR]) fragility index across the primary outcome of all trials was 5.45 (3.00 to 11.45). There was no statistical difference between the (1) types of outcomes (dichotomous vs. continuous; P = 0.710), (2) primary versus secondary pain outcomes ( P = 0.771), or (3) presence versus absence of trial conflict of interest ( P = 0.753). Indications with a median (IQR) fragility score greater than three included persistent spinal pain syndrome type 2 with a score of 8.00 (2.80 to 12.60), painful diabetic neuropathy with a score of 6.00 (3.00 to 11.80), complex regional pain syndrome with a score of 7.20 (4.62 to 81.50), mixed etiologies with a score of 9.00 (3.00 to 38.00), and other etiologies with a score of 3.00 (1.00 to 8.55). Conclusions: This study suggests that the majority of RCTs investigating primary pain outcomes after SCS therapy are robust with relatively high fragility scores. Reporting the fragility of outcomes in trials can provide a more comprehensive assessment of trial robustness and can further aid clinicians in interpreting trial results and making informed treatment decisions.

Abstract Introduction There is wide variation in male fertility preservation practices. While physician preference accounts for some of this diversity, practice patterns often reflect multiple extrinsic factors including patient demographics, equipment availability, laboratory protocols, and state law. Objective We sought to characterize national trends in sperm retrieval and storage across reproductive urology practices in the United States. Methods An anonymous 34-item survey characterizing provider demographics, practice settings, fertility preservation procedures, andrology laboratory practices, and cryopreservation expenses was designed. Practicing reproductive urologists were identified using information available through professional societies. Our survey was constructed using the Qualtrics platform and distributed electronically between October 2024 and May 2025. Results 39 responses were received by urologists practicing across 21 states (response rate: 21%, n=189). A majority (74%, n=29) of survey responders practiced at academic medical centers, with others practicing at non-academic hospitals (8%, n=3) and private practices (13%, n=5). The most common indications for fertility preservation reported included oncologic care (42%), gamete storage for planned ART (31%), transgender care (18%), pre-vasectomy sperm banking (10%), and pre-deployment banking for military personnel (5%). Nearly all providers performed microsurgical sperm retrievals (97%, n=38, Figure) and oncologic testicular sperm extractions (85%, n=33) when indicated. More than half of providers offered conventional testicular sperm extractions (72%, n=28), microsurgical epididymal sperm aspirations (59%, n=23), testicular sperm aspirations (56%, n=22), penile vibratory stimulation (54%, n=21), or percutaneous epididymal sperm aspirations (52%, n=20). Fewer providers offered post-mortem sperm retrieval (49%, n=19), pre-pubertal testicular tissue cryopreservation (36%, n=14), or electroejaculation (31%, n=12). Most respondents (62%, n=24) had access to an on-site andrology laboratory. Semen analyses were evaluated using manual (53%, n=20), computer-assisted (11%, n=4), or combinatorial methods (26%, n=10). Though many (37%, n=14) providers were uncertain about institutional costs for semen specimen processing, a plurality of respondents (40%, n=15) reported fees ranging from $100-500 with the remainder (23%, n=9) reporting fees exceeding $500. Respondents most frequently reported semen storage fees ranging between $100-300 per year (39%, n=15), while approximately a third (31%, n=12) estimated these costs to range between $300-600 per year. However, 18% (n=7) of respondents reported higher costs for specimen storage and 13% (n=5) were uncertain about the expense of this service. Conclusions This multi-institutional, geographically diverse survey reveals significant variation in reproductive urology practice patterns and cost associated with semen analyses and storage. Future studies will explore differences in practice patterns to better understand the factors influencing this variation and their effect on male reproductive healthcare. In the absence of society guidelines, reproductive urologists must collaborate, share best practices, and maintain price transparency to ensure sperm retrieval remains accessible and affordable. Disclosure No

Abstract Introduction Fertility preservation is an essential component to cancer survivorship. One third of male survivors experience infertility following gonadotoxic treatments, and expeditious preservation prior to therapy is recommended by oncology guidelines. However, this can be challenging given time constraints, lab expertise, and financial considerations. Objective We describe national practice patterns and identify barriers and facilitators regarding inpatient male fertility preservation. Methods An anonymous 34-item Qualtrics survey was sent to reproductive Urologists in the United States. Email addresses were obtained from public membership databases. Respondents were queried across several domains, including provider demographics, specific inpatient cryopreservation scenarios, and fertility preservation procedures. Results Thirty-nine (21%, n=39/189) responses were received. The majority of respondents were fellowship-trained reproductive urologists 89.7% (35). The majority (97.4%) of respondents offer microdissection testicular sperm extraction (mTESE) for fertility preservation, and many offer conventional TESE (71.8%), traditional ejaculated sperm cryopreservation (71.8%), or microsurgical epididymal sperm aspiration (59%). Only 30.8% of respondents offer electroejaculation. Respondents rate non-urology provider awareness of male cancer fertility preservation options at 5.05/10 on a Likert scale. Many (65%) respondents provide formal materials or education to nonurology providers to address this deficit. On average, respondents reported 2.6 inpatient oncofertility preservation consults per month (range 0-25, median=1). Most (60%) of respondents reported that &lt;25% of these patients ultimately complete inpatient preservation. Financial burdens (97%), logistical hurdles (97%), limited awareness (97%), and concern for delay of oncologic care (92%) were identified as the most common barriers for patients precluding fertility preservation. In addition, 85% of respondents also listed difficulty coordinating with other specialists as a barrier. On free-text queries, respondents identified facilitators of fertility preservation as automatically triggered consults, use of an urgent cryopreservation pager, formal fertility preservation pathway within the order set, and utilization of an inpatient coordinator as facilitators that aid in achieving timely fertility preservation prior to gonadotoxic therapies. Conclusions Despite all reproductive urologists offering cryopreservation services and education regarding the urgency and priority of inpatient fertility preservation, less than a quarter of patients complete this process during hospitalization prior to initiation of treatment. This remains the consequence of numerous patient, provider, and facility level barriers, even in systems with robust referral processes. Inpatient fertility preservation remains an underutilized and often missed opportunity. Multidisciplinary interventions are needed to address ongoing barriers. Disclosure No