Citations

ABSTRACT Point-of-care ultrasonography (POCUS) has rapidly evolved from a niche technology to an indispensable tool across medical specialties, including nephrology. This evolution is driven by advancements in technology and the visionary efforts of clinicians in emergency medicine and beyond. Recognizing its potential, medical schools are increasingly integrating POCUS into training curricula, emphasizing its role in enhancing diagnostic accuracy and patient care. Despite these advancements, barriers such as limited faculty expertise and ‘lack of’ standardized guidelines hinder widespread adoption and regulation. The International Alliance for POCUS in Nephrology (IAPN), through this position statement, aims to guide nephrologists in harnessing the diagnostic power of POCUS responsibly and effectively. By outlining core competencies, recommending training modalities and advocating for robust quality assurance measures, we envision a future where POCUS enhances nephrology practice globally, ensuring optimal patient outcomes through informed, evidence-based decision-making. International collaboration and education are essential to overcome current challenges and realize the full potential of POCUS in nephrology and beyond.

AbstractSmoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high‐risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high‐risk SMM patients remains an important clinical need. In this study, we present the 3‐dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20‐2‐20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20‐2‐20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.

ABSTRACT Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Context.— Mesothelioma is an uncommon tumor that can be difficult to diagnose. Objective.— To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma. Data Sources.— Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks. Conclusions.— There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.

PURPOSE KRAS is the most commonly mutated driver oncogene in non–small cell lung cancer (NSCLC). Sotorasib and adagrasib, KRAS G12C inhibitors, have been granted accelerated US approval; however, hepatotoxicity is a common side effect with higher rates in patients treated with sotorasib proximal to checkpoint inhibitor (CPI) therapy. The aim of this study was to assess the feasibility and safety of adagrasib after discontinuation of sotorasib because of treatment-related grade 3 hepatotoxicity through real-world and clinical cases. METHODS Medical records from five patients treated in real-world settings were retrospectively reviewed. Patients had locally advanced or metastatic KRAS G12C -mutated NSCLC and received adagrasib after sotorasib in the absence of extracranial disease progression. Additional data were collected for 12 patients with KRAS G12C -mutated NSCLC enrolled in a phase Ib cohort of the KRYSTAL-1 study and previously treated with sotorasib. The end points associated with both drugs included timing and severity of hepatotoxicity, best overall response, and duration of therapy. RESULTS All patients were treated with CPIs followed by sotorasib (initiated 0-64 days after CPI). All five real-world patients experienced hepatotoxicity with sotorasib that led to treatment discontinuation, whereas none experienced treatment-related hepatotoxicity with subsequent adagrasib treatment. Three patients from KRYSTAL-1 transitioned from sotorasib to adagrasib because of hepatotoxicity; one experienced grade 3 ALT elevation on adagrasib that resolved with therapy interruption and dose reduction. CONCLUSION Adagrasib may have a distinct hepatotoxicity profile from sotorasib and is more easily combined with CPIs either sequentially or concurrently. These differences may be used to inform clinical decisions regarding an initial KRAS G12C inhibitor for patients who recently discontinued a CPI or experience hepatotoxicity on sotorasib.

Abstract Patient‐reported quality‐of‐life (QoL) and carer impacts are not reported after leucine‐rich glioma‐inactivated 1‐antibody encephalitis (LGI1‐Ab‐E). From 60 patients, 85% (51 out of 60) showed one abnormal score across QoL assessments and 11 multimodal validated questionnaires. Compared to the premorbid state, QoL significantly deteriorated ( p < 0.001) and, at a median of 41 months, fatigue was its most important predictor ( p = 0.025). In total, 51% (26 out of 51) of carers reported significant burden. An abbreviated five‐item battery explained most variance in QoL. Wide‐ranging impacts post‐LGI1‐Ab‐E include decreased QoL and high caregiver strain. We identify a rapid method to capture QoL in routine clinic or clinical trial settings.

Abstract Recent advances in the field of immuno‐oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high‐throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi‐marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Background: Sodium-glucose co-transport-2 (SGLT2) inhibitors have been shown to reduce clinical events and improve health status (symptoms, function, and quality of life) in patients with HF across the range of EF. Baseline kidney dysfunction is common in HF, complicates HF management, and is strongly linked to worse health status. Aim: The study objective was to assess whether the treatment effects of dapagliflozin on health status vary based on baseline eGFR. Methods: Patient-level data were pooled from the DEFINE-HF (N = 263 participants with EF < 40%) and PRESERVED-HF trials (N = 324 participants with EF > 45%). Both were double-blind, randomized trials of dapagliflozin vs. placebo, enrolling participants with NYHA class II or higher and elevated natriuretic peptides. The primary endpoint for this analysis was Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CCS) at 12 weeks. Interaction of dapagliflozin effects on KCCQ-CCS by baseline eGFR (mL/min/1.73m 2 ) was assessed as categorical (i.e., eGFR <60 vs. > 60) and continuous variables. Results: Across both trials there were 583 (99.3%) participants with available baseline eGFR. The median (25 th , 75 th ) eGFR was 59 (46,77). Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference, +5.0 points, 95% Confidence Interval [CI] 2.6-7.5; p-value <0.001), and this was consistent in participants with an eGFR > 60 (+6.0 points, 95% CI 2.4-9.7; p=0.001) and <60 (+4.1 points, 95% CI 0.5-7.7; p=0.025) (p-interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS were robust across eGFR when modeled continuously (p-interaction = 0.46) ( Figure ). There was no heterogeneity of treatment effects when analyzing other KCCQ domains based on eGFR categorically or continuously (all p-interaction = NS). Conclusion: Treatment with dapagliflozin for 12 weeks led to significant and consistent improvements in health-related quality of life in patients with HF across a wide range of eGFRs.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.