Citations

Abstract Objective Epilepsy duration is a modifiable risk factor in the outcome of definitive epilepsy surgery; however, an analogous effect in palliative procedures has not been shown. We reviewed the Pediatric Epilepsy Surgery Database data for an association between epilepsy duration and seizure reduction in palliative procedures. Methods Patients enrolled between January 2018 and April 2025 who underwent their first epilepsy surgery with palliative intent with 6 months of follow‐up were included. Procedures included neuromodulation, corpus callosotomy, hemispherotomy, lesionectomy, and lobectomy where surgical intent was not seizure freedom. Outcomes of seizure freedom, 90% seizure reduction, and 50% seizure reduction were considered at 6–12 months and >12 months from surgery. Duration from epilepsy onset to surgery was compared for patients above and below each outcome threshold at each time point. Logistic regression analysis for the association between epilepsy duration and seizure reduction adjusted for potential confounders including procedure type, etiology, and other clinical factors. Logistic regression analysis was performed on the overall cohort and subgroups of patients with each procedure. Results A total of 588 patients were included. Initial univariate analysis suggested that epilepsy duration at time of surgery was significantly associated with seizure freedom and 90% seizure reduction at both 6–12 months and >12 months. After adjusting for confounders, only seizure freedom at >12 months was significantly associated with duration of epilepsy. When individual procedures were considered, only lobectomy was sensitive to duration of epilepsy in multivariate analysis, with significant impacts on >50% and >90% seizure reduction at >12 months. Lesional epilepsy predicted seizure freedom at >12 months. Neuromodulation and corpus callosotomy were less likely to achieve seizure reduction than other procedures. Significance We did not find an association between early epilepsy surgery and seizure reduction. This reflects the heterogeneity of our population, including different types of surgical procedures and lesional and nonlesional epilepsies.

Long-established prostate cancer cell lines provide limited insight into how contemporary early prostate cancer evolves into drug-resistant and neuroendocrine-like refractory disease. Patient-derived three-dimensional (3D) ex vivo models may better preserve this transition. Here, we found that 8 of 10 magnetic resonance imaging-guided biopsy specimens from patients with early-stage prostate cancer generated sustained 3D tumor spheroid cultures. After 12 weeks of enzalutamide selection, only one patient-derived culture acquired a resistant phenotype with treatment-emergent neuroendocrine prostate cancer (t-NEPC)-like features, including increased chromogranin A (CgA) and synaptophysin (SYP); reduced androgen receptor (AR), prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA); and conversion from compact spheroids into irregular resistant aggregates. During this transition, WD repeat and SOCS box-containing protein 1 (WSB1) increased, whereas PSMA progressively decreased. WSB1 silencing restored PSMA, AR, and PSA expression and reduced neuroendocrine-associated features. A similar WSB1 dependency was observed in enzalutamide-resistant LNCaP cells, the castration-resistant prostate cancer model 22Rv1, and the neuroendocrine/small-cell prostate cancer model NCI-H660. Mechanistically, WSB1 functioned as a SOCS box-dependent E3 ubiquitin ligase adaptor that promoted PSMA ubiquitination and degradation. SOCS box deletion or T380A mutation impaired this process, while Aurora kinase A (AURKA) inhibition reduced WSB1-dependent PSMA ubiquitination. WSB1 depletion, AURKA inhibition with alisertib, and combined AURKA inhibition with EZH2 suppression reduced resistant aggregate growth and increased apoptosis-associated markers in patient-derived enzalutamide-resistant neuroendocrine-like spheroids and related models. These findings nominate the AURKA–WSB1–PSMA axis as a therapeutic vulnerability in refractory prostate cancer.

Summary Iron deficiency (ID) is often overlooked in patients with haematological malignancies due to other potential aetiologies. Daratumumab, an anti‐cluster of differentiation 38 (anti‐CD38) monoclonal antibody, is commonly used for treating multiple myeloma (MM) in the upfront and relapsed/refractory settings. Although anaemia is a common haematological toxicity associated with daratumumab, the contribution of ID in MM patients has not been systematically investigated. We conducted a retrospective case–control study to evaluate the prevalence of ID in newly diagnosed MM (NDMM) patients. Cases were patients receiving daratumumab, ixazomib, lenalidomide and dexamethasone (Dara‐IRD, n = 55). We compared this group with an age‐ and sex‐matched cohort of patients with NDMM who received bortezomib, lenalidomide and dexamethasone (VRD, n = 20) as induction therapy. At 1‐year, nearly 50% of Dara‐IRD‐treated patients met the criteria for ID (ferritin <30 mcg/L) compared with none of the VRD‐treated controls. All Dara‐IRD‐treated patients had a decrease in ferritin at 1‐year from baseline compared with only 45% of VRD‐treated patients. These findings identify a marked clinical signal of ID among NDMM patients receiving daratumumab‐based treatment. Although the study design does not establish causality or exclude regimen‐related confounding, it highlights the need for increased awareness of the importance of monitoring iron status in MM patients treated with daratumumab‐containing regimens.

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