Citations

Abstract Primary angiitis of the central nervous system is an extremely rare diagnosis, with an incidence of 2.4 cases per 1,000,000 person-years. The exact cause of PACNS remains unknown, and typically cases present with a long prodrome. It is a diagnosis of exclusion, and various infectious, autoimmune, and malignant processes must be excluded prior to final diagnosis. Given the rarity of this condition, there is often a delay in diagnosis that can range from 6 to 23 months. It is imperative that all clinical providers be aware of this diagnosis when managing patients who present with insidious and non-specific neurological symptoms. We present a case of PACNS that responded well to a therapeutic regimen of high-dose steroids and cyclophosphamide.

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.

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient and sustainable fashion. Objectives: 1) Define the current status of IS; 2) Define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and 3) Develop a robust and broad research agenda incorporating IS methodology into the programs. Evidence Review: ADQI XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on 1) IS definitions and methods applicable to AKI and acute kidney care; 2) IS literature in AKI and acute kidney care; 3) Innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; 4) IS methods in resource-limited settings; and 5) Recommendations to identify and evaluate EBPs that are ready for implementation or de-implementation. Prior to the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the two-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. Conclusions and Relevance: We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/de-implementation of EBPs in clinical care.

Abstract Frailty influences treatment outcomes in older patients with multiple myeloma (MM), yet existing frailty tools capture limited geriatric domains and are incompletely studied in the context of contemporary therapies. We prospectively evaluated patient-reported comprehensive geriatric assessment (CGA) domains and their associations with treatment toxicity and patient-reported outcomes (PRO) in older adults with MM. Patients aged ≥60 years with newly diagnosed or relapsed/refractory MM initiating a new therapy completed electronic CGA and PRO questionnaires at baseline and 4 months. Outcomes included clinician- and patient-reported treatment toxicity, treatment adaptations, health care use, and health-related quality of life (HRQOL). A cumulative deficit frailty index (FI) was derived from CGA and HRQOL domains. Among 90 patients (mean age, 72 years), geriatric impairments were common, particularly physical function domains. High-grade nonhematologic toxicities were significantly associated with older age, comorbidities, patient-reported functional limitations, and anxiety. Toxicity rates on the PRO version of the Common Terminology Criteria for Adverse Events (CTCAE) were higher than on CTCAE, highlighting a discordance between physician- and patient-reported treatment toxicity. Frailty was present in 22% and associated with worse baseline HRQOL and increased high-grade nonhematologic toxicity but not treatment adaptations or health care use. Average CGA and HRQOL scores remained stable over 4 months, although individual trajectories varied. Patient-reported geriatric impairments are prevalent in older adults with MM and strongly associated with nonhematologic toxicities even in the contemporary treatment era. Physician-reported CTCAE may not fully reflect patients' symptom burden. Heterogeneity in individual geriatric trajectories during treatment emphasize the need for longitudinal assessment. This study was registered at www.clinicaltrials.gov as NCT05918185.

Abstract Measurable residual disease (MRD) is a powerful prognostic tool in multiple myeloma, but predictors of achieving MRD negativity after autologous stem cell transplantation (ASCT) are not well defined. We studied 814 patients who achieved at least a very good partial response after ASCT between January 2016 and January 2023 and underwent MRD assessment by next-generation flow cytometry. Overall, 387 (48%) achieved MRD negativity after ASCT. The presence of t(11;14) (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.4–3.2; P&lt; .01) and pretransplant response less than complete remission (OR, 2.1; 95% CI, 1.2-3.7; P&lt; .01) independently predicted MRD positivity. Patients who were MRD positive had inferior progression-free survival (PFS; hazard ratio [HR], 1.99; 95% CI, 1.53-2.58; P&lt; .001) and overall survival (HR, 1.62; 95% CI, 1.10-2.28; P = .009). Despite lower MRD-negative rate, 5-year PFS was similar among t(11;14) MRD positive (58%) and patients who were MRD negative (63%; P = .12). In patients who were MRD negative, the 5-year PFS was 73% in those without ≥2 HRCA compared with 55% in those with ≥2 HRCA (HR 1.9, 95% CI 1.2–3.3; P = .01). In the MRD-positive cohort, 5-year PFS was 53% in patients without ≥2 HRCA vs 17% in those with ≥2 HRCA (HR, 2.4; 95% CI, 1.6-3.6; P&lt; .01). In addition, higher residual clonal plasma cell burden within MRD-positive disease was associated with inferior PFS (HR, 2.4; 95% CI, 1.2-6.9; P = .002). This study highlights that the presence of t(11;14) independently predicts MRD positivity after ASCT, although it does not significantly affect prognosis in this subgroup.

Solitary plasmacytomas (SPs) are rare localized tumors of clonal plasma cells, either in the bone (solitary bone plasmacytoma) or in soft tissue/extraosseous (extramedullary) with either no or with minimal bone marrow (BM) infiltration (<10% clonal plasma cells by immunohistochemistry) and no evidence of systemic involvement or myeloma defining events. Approximately 50% of SPs will progress to symptomatic myeloma within 5 years after initial definitive local radiotherapy. Increased availability of improved diagnostic and monitoring tools has increased the sensitivity of detection of additional lesions and marrow involvement and has implications for the follow-up strategy after treatment. Thus, the definitions and requirements for the diagnosis and follow-up of SPs are evolving. The diagnosis of SP requires the careful exclusion of multiple myeloma (MM) that would require systemic therapy, by using all the available methods to detect systemic disease (advanced imaging, sensitive BM assessment methods, blood and urine tests). Local radiotherapy remains the mainstay of therapy, and despite the availability of innovative drugs for MM, the clinical benefit of systemic therapy currently remains poorly defined. The International Myeloma Working Group provides here updated recommendations for the diagnosis, evaluation, treatment, and response assessment of patients with SPs, incorporating recent data and advances in diagnostic tools.

Background The current classification of pulmonary hypertension (PH), based largely on expert opinion, has limitations in prognostication and guiding therapies. We hypothesize that novel PH clusters that predict survival will reveal mechanistic phenotypes associated with biomarkers of vascular health across all PH groups. Methods We first identify novel PH clinical clusters by performing unsupervised clustering analysis on the CC‐PH (Cleveland Clinic PH) registry (N=1529). We develop classification models to predict the new PH clusters and then apply them to the multicenter PVDOMICS (Pulmonary Vascular Diseases Phenomics) cohort (N=853) for validation. We compare transplantation‐free survival across the new PH clusters. We quantify metabolites of the arginine‐nitric oxide pathway and D‐dimer levels and calculate global arginine bioavailability (arginine/[ornithine+citrulline]) to assess endothelial function and activation in the new clusters and link these biomarkers to clinical outcomes. Results Clustering analysis identify 3 clear clusters in CC ‐ PH that are validated in PVDOMICS and outperform conventional classifications in predicting transplantation‐free survival. The phenotype associated with the worst survival is characterized by reduced lung diffusion capacity, decreased arginine bioavailability and nitrate levels, and elevated D‐dimer levels, consistent with loss of pulmonary microcirculation and endothelial dysfunction. Conclusions We identify new informative PH phenotypes associated with mortality and defined by biomarkers of endothelial function and activation. Loss of endothelial health and pronounced pulmonary vascular rarefication contribute more substantially to mortality across the spectrum of PH than right heart function. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02980887.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Abstract Introduction Underwater endoscopic mucosal resection (uEMR) technique has gained popularity for removal of large non-pedunculated colorectal polyps (LNPCPs) due to high en-bloc resection rates and lower recurrence rates. However, there is no information regarding outcomes of uEMR for giant colorectal polyps. Therefore, we aimed to evaluate the outcomes of uEMR for giant colorectal polyps across multiple centers in North America. Methods We conducted a multicenter retrospective study of adults with giant colorectal polyps undergoing uEMR between January 2019 and November 2025. Giant colorectal polyps were defined as LNPCPs ≥40 mm. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were severe adverse events (SAEs) and predictors of technical success, recurrence, and SAEs. Results A total of 137 polyps, with mean polyp size 47.6 mm were included. Majority of the lesions were located in right colon (61%, n = 83) with the most common histopathology being high-grade dysplasia (HGD) (31.4%, n = 43). Technical success was achieved in 90.5% (n = 124) with en-bloc resection rate of 11.7% (n = 16). Polyp fibrosis (OR: 0.08) and HGD (OR: 0.15) were independent predictors of inability to achieve technical success. Of 92 (67.1%) patients with follow-up, recurrent polyp was present in 8.7% (n = 8). SAEs were noted in 9.5%, consisting of delayed bleeding (9.5%, n = 13), while no delayed perforation or post polypectomy syndrome was noted. Discussion Our study demonstrates that uEMR is technically feasible for the removal of giant colorectal polyps with an acceptable safety profile and recurrence rate.

ABSTRACT Background Implementation of remote robotic‐assisted surgery (rRAS) has the potential to significantly improve access to high‐quality surgical care for patients worldwide. Advances in robotic systems and telecommunications now enable highly reliable, low latency, and cybersecure connectivity. These technological developments, together with the broader adoption of telemedicine, have driven an increasing interest in the implementation of rRAS. Methods The Clinical Robotic Surgery Association (CRSA) convened a conference to develop international clinical recommendations for rRAS using the Danish Model of Consensus. The society identified five key issue categories and invited a panel of experts to address specific questions for each. Panel members and a jury of 10 unbiased, non‐expert in rRAS professionals participated in a day‐long conference on November 19, 2025 (Los Angeles, USA). During the conference, participants presented, discussed, and reached consensus on specific guidelines relevant to each category. Immediately after the conference, the jury reviewed and approved the recommended guidelines. Results Multiple recommendations were approved for each of the following categories: Operating Models, Roles and Responsibilities (2 recommendations), Clinical Pathway (2 recommendations), Emergency Management (8 recommendations), Technical Considerations (5 recommendations), and Medico‐legal and Ethical Considerations (4 recommendations). Conclusions There was consensus that with recent advances in telecommunication and robotic technologies, rRAS can be offered safely and effectively if the identified safeguards are realized. Adoption of rRAS is expected to continue advancing rapidly.