Citations

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is commonly encountered in older individuals. MGUS, by definition, is a benign finding where an expanded population of clonal plasma and B-cells produces a monoclonal antibody that is a biologically inactive. Even in patients with overt plasma cell neoplasms such as multiple myeloma, the monoclonal antibody is often a marker of disease burden but not pathogenic except in light chain cast nephropathy. However, there is a growing recognition that, in rare cases, clonal cells and/or monoclonal gammopathy not meeting criteria for hematologic malignancy can be pathogenic drivers of disease. These MGUS syndromes have been termed monoclonal gammopathies of clinical significance (MGCS), a larger umbrella under which sits the monoclonal gammopathies of renal significance (MGRS). In this review, we focus on MGCS entities beyond standard MGRS and provide a mechanism-based classification centered on the pathogenic nature of the paraprotein rather than on clonal disease burden. We highlight MGCS entities of relevance to nephrologists, including POEMS syndrome, TEMPI syndrome, monoclonal gammopathy-associated systemic capillary leak syndrome, and hematologic autoantibody-mediated disorders. Awareness and recognition of these rare processes are ultimately essential for accurate diagnosis and patient management.

Objective: To evaluate factors associated with the conversion of robotic-assisted partial nephrectomy (RAPN) to open partial nephrectomy (OPN) and radical nephrectomy (RN). Methods: We retrospectively reviewed 775 consecutive RAPNs from a single surgeon. Perioperative factors were evaluated for association with RAPN conversion such as Mayo Adhesive Probability (MAP) score, length of stay (LOS), and operative time (OT). A logistic regression model was utilized to evaluate factors associated with conversion and reported as odds ratio (OR) with 95% confidence intervals. Continuous and categorical variables were analyzed through the Wilcoxon rank-sum and chi-square tests. Results: Thirty-two (4.1%) patients had a conversion including 19 (2.5%) to OPN and 13 (1.7%) to RN. OPN conversions were related to bleeding ( n = 7), inability to dissect perinephric fat ( n = 4), liver retraction ( n = 1), and failure to secure renal hilum/progress ( n = 7). In contrast, conversions to RN were due to tumor involvement of the renal vein ( n = 3) or ureter ( n = 5) and inability to achieve negative margins ( n = 5). Patients in the conversion cohort were more likely to have larger tumor size (3.7 vs 2.8 cm; p < 0.001) and higher MAP score (3.0 vs 2.0; p = 0.04). Median LOS was higher in the conversion group (3.0 vs 2.0 days; p = 0.003). Conversions were associated with postoperative complications (28.1% vs 13.7%; p = 0.023). After adjusting tumor size in our regression model, longer OT and dissection time were statistically higher in the conversion group (OR = 2.19 [1.50–3.21]; p < 0.001 and OR = 2.67 [1.82–3.94]; p < 0.001, respectively). Conclusions: Larger tumor size and higher MAP score were associated with conversions during RAPN. Conversions were associated with higher LOS, longer OT, and postoperative complications.

Abstract Background Right ventricular apical (RVA) pacing often leads to interventricular dyssynchrony and pacing-induced cardiomyopathy. Conduction system pacing (CSP), particularly Left Bundle Branch Area Pacing, provides a physiologic alternative. In Limited Resource Countries (LRCs) like Thailand, Cardiac Resynchronization Therapy (CRT) under-penetration persists due to high costs and a shortage of operators skilled in coronary venous anatomy. Objective To share the experience and provide clinical update of CSP as a sustainable, cost-effective physiological pacing strategy to improve access to advanced arrhythmia management in resource-constrained environments. Methods This review explores the implementation of minimalist protocols and CSP-based CRT. Scalability strategies include specialized training programs, device reprocessing, and the establishment of regional longitudinal registries to bridge infrastructure gaps. Results CSP-based CRT can reduce device costs by nearly 50% compared with traditional triple-lead systems. This modality effectively mitigates the hemodynamic risks of RVA pacing while bypassing the technical and financial barriers of conventional CRT. Discussion Despite its advantages, CSP adoption requires overcoming infrastructure challenges, specifically the lack of automated remote monitoring. Optimizing clinical outcomes in LRCs necessitates standardized training, robust data collection, and innovative resource management to ensure equitable access to life-saving technology.

ABSTRACT Anti‐Spike monoclonal antibodies (mAbs) progressively lost efficacy during the COVID‐19 pandemic due to the emergence and predominance of resistant SARS‐CoV‐2 variants. By contrast, high‐titre COVID‐19 convalescent plasma (CCP) collected from vaccinated donors recently recovered from infection provides a polyclonal source of antibodies that remains effective in clearing SARS‐CoV‐2 in immunosuppressed patients, unable to mount an adequate immune response against the virus. We conducted a systematic review and individual participant data meta‐analysis to examine the effect of CCP in immunocompromised patients persistently positive for SARS‐CoV‐2 viraemia following mAb therapy, and to evaluate possible biological factors associated with a favourable outcome. Electronic databases were searched for studies published from January 2020 to January 2026. All studies including eligible cases were considered in the systematic review. Unpublished cases were also collected from investigators of the selected studies. The protocol was registered at PROSPERO (CRD420251142891). Forty‐seven cases (30 cases from 12 published studies and 17 unpublished cases) were included. In 33 out of 47 patients (70.2%) with a mAb‐resistant infection, SARS‐CoV‐2 clearance occurred following CCP transfusion, with a mean of 2.7 CCP units administered. In logistic regression, total CCP volume transfused was positively associated with SARS‐CoV‐2 clearance. In conclusion, CCP transfusion was associated with SARS‐CoV‐2 clearance in persistently positive immunocompromised patients following failure of anti‐Spike mAb therapy.

Abstract Normal scapulothoracic function relies on a delicate balance among several periscapular muscles and is essential for shoulder motion. Disturbance in this balance can lead to abnormal motion, which can impair shoulder function, leading to pain and discomfort. A thorough scapular examination requires an accurate physical assessment and the ability to identify pathologies, such as muscle paralysis (e.g., trapezius or serratus anterior) and hyperactivity (e.g., pectoralis minor). Overall, a comprehensive approach to the physical examination is critical in accurately diagnosing and effectively treating shoulder and scapular pathologies. The purpose of this technical note is to provide a concise, standardized methodology for performing a comprehensive scapular examination, focusing on key clinical tests, anatomical landmarks, and motion patterns.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are associated with immune-related adverse events, including ICI–associated acute kidney injury (ICI-AKI). ICI-AKI presents diagnostic and management challenges and can influence decisions regarding immunosuppression and ICI rechallenge, with important implications for both kidney and cancer outcomes. An international, multidisciplinary panel convened at the 34th Acute Disease Quality Initiative (ADQI) consensus conference in September 2024. Systematic literature searches of PubMed were conducted to identify studies on the epidemiology, mechanisms, diagnosis, management, rechallenge, and outcomes of ICI-AKI. The meeting followed the established ADQI process and used a modified Delphi method to achieve consensus. Evidence was reviewed and appraised by workgroups, and consensus statements were developed through structured discussion and voting. Observational data suggest that AKI occurs in up to 20% of patients receiving ICIs, with ICI-AKI accounting for approximately 2%–5% of cases. Acute tubulointerstitial nephritis is the most common lesion, observed in 80%–90% of biopsies, although glomerular diseases are increasingly recognized. No clinical features reliably distinguish ICI-AKI from other causes of AKI, and kidney biopsy remains the diagnostic gold standard. Emerging urinary, circulating, and imaging biomarkers show promise but are not yet ready for routine clinical use. Early glucocorticoid initiation (within 3 days of ICI-AKI diagnosis versus >3 days after diagnosis) is associated with higher rates of kidney recovery, although optimal dosing and duration remain uncertain. Recurrent ICI-AKI occurs in fewer than 20% of patients undergoing ICI rechallenge. Management of high-risk populations, including kidney transplant recipients and patients with autoimmune disease or advanced CKD, requires individualized, multidisciplinary decision-making. ICI-AKI is an important and potentially reversible complication of cancer immunotherapy; these consensus statements provide a framework for diagnosis and management, support cautious ICI rechallenge in selected patients, and identify priorities for future research.

ABSTRACT Cutaneous manifestations of chronic lymphocytic leukemia (CLL) are heterogeneous and may result from leukemic infiltration, secondary malignancies, infectious complications, or reactive inflammatory processes. Reactive angioendotheliomatosis (RAE) is a rare vascular proliferation that has only infrequently been reported in association with hematologic malignancies. We describe a 58‐year‐old man with high‐risk relapsed/refractory CLL harboring TP53 mutation and del(17p) who developed rapidly enlarging, fungating cutaneous lesions involving the right thumb, upper arm, and additional sites despite multiple prior therapies, including fludarabine, cyclophosphamide, rituximab, ibrutinib, and venetoclax. Histopathologic evaluation demonstrated dermal vascular proliferation with endothelial marker positivity (CD31, CD34, ERG, and vimentin), consistent with RAE and without evidence of leukemic infiltration. The lesions were refractory to local supportive measures but showed marked regression following treatment with CD19‐directed chimeric antigen receptor (CAR) T‐cell therapy using lisocabtagene maraleucel. Notably, cutaneous remission despite persistent measurable residual disease and eventual systemic relapse requiring allogeneic hematopoietic cell transplantation. This discordance suggests that regression of RAE may be mediated through immune modulation and alteration of inflammatory or angiogenic pathways rather than direct elimination of cutaneous leukemia. To our knowledge, this is among the first reports describing resolution of paraneoplastic RAE following CAR T‐cell therapy in CLL, and it highlights the broader immunomodulatory effects of cellular immunotherapy beyond direct antitumor activity. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission

Abstract Objectives This study used both researcher and patient perspectives to identify high-priority research questions related to clinical reasoning. Methods This study integrates findings from two previously published research prioritization exercises aimed at advancing the science of diagnostic safety, focusing on questions relevant to clinical reasoning. In Study 1 (April 2019), 97 researchers submitted 177 unique research questions that could be useful “to reduce patient harm in the diagnosis process”. In Study 2 (November 2019), 41 patients/caregivers/advocates submitted 84 unique research questions on the same topic. In an in-person meeting, a subset of these participants identified 81 of these questions as high-priority (51 from Study 1; 30 from Study 2). For the current study, five investigators identified questions that focused on clinical reasoning, first independently and then by consensus. They then categorized the clinical reasoning questions into inductively identified themes. Results Twenty-nine of the 81 high-priority research questions addressed clinical reasoning and were categorized into 5 themes: understanding clinical reasoning and cognition (12 questions), decision support/technology (6 questions), team-based decision making (5 questions), how to learn from cases/scenarios (3 questions), and patient engagement (3 questions). Questions addressed a range of basic/foundational science and clinical applications, and involved individuals, teams, and/or systems. Conclusions Identification of high-priority clinical reasoning research questions can help medical educators, clinicians, researchers, and funders catalyze research and discovery of interventions to improve clinical reasoning and ultimately improve patient outcomes.

Background:The development of symptoms or left ventricular dysfunction in severe aortic stenosis (AS) is associated with high morbidity and mortality. While elective transcatheter aortic valve replacement (TAVR) is supported by robust randomized evidence, data on TAVR performed in non-elective settings (urgent, emergent, or salvage) remain limited and heterogeneous. In these settings, outcomes may be influenced more by baseline clinical severity than by procedural factors. This study aimed to systematically evaluate the safety and effectiveness of non-elective TAVR and to compare the associated outcomes with those of elective TAVR.Methods:This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered with PROSPERO. The PubMed, Embase, and Scopus databases were searched for studies published after 2002 evaluating urgent, emergent, or salvage TAVR in adult patients with severe AS. Eligible studies were required to include elective TAVR as a comparator. Outcomes included mortality and major procedural complications. Prespecified era-based analyses and sensitivity analyses excluding studies at critical risk of bias were performed. Risk of bias was assessed using the ROBINS-I tool.Results:A total of 17 observational studies published between 2015 and 2025 were included, comprising 215,141 patients. Compared with elective patients, those undergoing non-elective TAVR had more advanced heart failure, higher NYHA class, greater comorbidity burden, and higher surgical risk scores, whereas baseline echocardiographic severity of AS was similar. Pooled outcomes for non-elective TAVR showed in-hospital, 30-day, and 1-year mortality rates of 5.1%, 12.4%, and 26.7%, respectively. Non-elective TAVR was associated with higher mortality at all time points compared with elective procedures; meanwhile, rates of stroke, vascular complications, and permanent pacemaker implantation were similar, while major bleeding and acute kidney injury were more frequent. Era-based analyses showed a stable relative mortality risk over time.Conclusions:Although non-elective TAVR is associated with worse outcomes than elective procedures, these differences appear to be largely driven by baseline clinical severity rather than by the transcatheter intervention. In unstable patients with severe AS, non-elective TAVR remains the most effective definitive treatment option compared with balloon aortic valvuloplasty or conservative management.The PROSPERO Registration:CRD420251239620, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251239620.

ABSTRACT This study aims to identify and characterize fenestrations in the aortic and pulmonary valves using an endoscopic approach and compare their prevalence and morphology in adult and fetal hearts. The research explores whether these fenestrations are congenital or acquired and their potential clinical implications. We analyzed 41 adult human hearts (mean age: 74.25 years; range: 62–92) and 97 fetal human hearts (mean gestational age: 26 weeks; range: 12–40). Specimens were preserved in alcohol‐phenol‐formaldehyde and examined using a Stryker 5 mm 0 degree endoscope to visualize valve structures in situ, followed by post‐endoscopic dissection. Two independent investigators assessed the specimens for fenestration prevalence, distribution, and morphology, categorized into ovoid, filamentous, and fenestrated types. Fenestrations were absent in all fetal hearts. Fenestrations were identified in 75.61% of adult hearts (31/41), with 74 fenestrations observed in total. Of these, 41 were in the pulmonary valve and 33 in the aortic valve. Ovoid fenestrations predominated in both valves (aortic: 76.3%, pulmonary: 85%), with significant distribution along leaflet edges, particularly in the left coronary and semilunar leaflets. No correlation with age or sex was found. The findings from this study suggest that valve fenestrations are more likely to be acquired postnatally, rather than representing congenital anomalies. The complete absence of fenestrations in all fetal heart specimens, contrasted with their high prevalence in adult hearts, supports this hypothesis. While our results do not directly prove a causal relationship, they align with prior literature proposing that biomechanical factors, such as cumulative leaflet stress, turbulent flow, and repeated coaptation, may contribute to the formation of fenestrations over time. These insights into the prevalence, morphology and leaflet distribution of fenestrations provide a valuable foundation for future research investigating their etiology, clinical significance, and potential role in valve dysfunction.