Citations

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

Purpose To evaluate return‐to‐sport (RTS) rates and patient‐reported outcome measures (PROMs) following hip arthroscopic labral repair for femoroacetabular impingement in active basketball players with a minimum of 2‐year follow‐up. Methods All patients who were active basketball players and underwent hip arthroscopy with labral repair for femoroacetabular impingement from 2009 to 2022 were identified. Patients were evaluated for postoperative RTS and revision surgery at a minimum 2‐year follow‐up. RTS was defined as resuming basketball participation, at any level. Modified Harris Hip Score (mHHS), Hip Outcome Score‐Activities of Daily Living (HOS‐ADL) and Sport (HOS‐Sport), and surgery satisfaction were also collected. Results Sixty‐seven hips in 54 athletes (29 male, 25 female) with a mean age of 22.2 years (range 13‐39 years) were included. Eighty‐six (86%) were recreational or high school basketball players. There was significant improvement in all PROMs from baseline to a minimum 2‐year follow‐up (all P < .001). After excluding for athletes who did not RTS for nonmedical reasons, 78% of athletes returned to basketball following hip arthroscopy. Including patients who cited nonmedical reasons for not returning, the overall RTS rate was 65%. Athletes who RTS had significantly higher mHHS ( P = .012), HOS‐ADL ( P = .006), and HOS‐Sport ( P = .002), as well as lower visual analog scale pain (2.2 vs 3.4, P = .037) than those who did not RTS. Calculated minimal clinically important difference values were 8.3 for mHHS, 7.2 for HOS‐ADL, and 13.4 for HOS‐Sport. Anchor‐based patient acceptable symptom state calculations yielded thresholds of 83.5 for mHHS, 92.6 for HOS‐ADL, and 79.2 for HOS‐Sport—with 70%, 63%, and 67% of patients achieving these thresholds, respectively. Conclusions Basketball players who undergo hip arthroscopic labral repair for femoroacetabular impingement show significant improvements in PROMs with 78% RTS rate at a minimum 2‐year follow‐up. Although many athletes discontinued basketball for reasons unrelated to the hip, 18% cited hip issues. Basketball players who successfully return to basketball report higher PROMs than nonreturners, and cohort‐specific minimal clinically important difference analysis indicates that most athletes achieve clinically meaningful improvements. Level of Evidence Level IV, therapeutic retrospective case series.

Abstract Rationale Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic progressive pulmonary fibrosis and high mortality. Genetic markers, summarized into a polygenic risk score (PRS), associate with IPF in well-phenotyped research cohorts. Objectives To evaluate the performance of the PRS using real-world data from routinely captured electronic healthcare records. Methods We conducted an observational study evaluating the association of a PRS for IPF with electronic healthcare record diagnosis of IPF as well as lung transplant-free survival in four independent cohorts; the Mass General Brigham Biobank (MGBB), Mayo Clinic Biobank (MCBB), Mayo Clinic Tapestry Cohort (Tapestry), and U.K. Biobank (UKBB). We used multivariable logistic regression and multivariable Cox proportional hazards models adjusting for age, gender, and principal components of ancestry. The cohorts then underwent fixed and random effects meta-analysis. Measurements and Main Results Of 37,709; 44,195; 43,202; and 447,422 participants from MGBB, MCBB, Tapestry and UKBB respectively, 1,015 (2.7%) 2,879 (6.5%), 1,310 (3.0%), and 2,742 (0.6%) participants had an IPF diagnosis. Meta-analysis demonstrated a high-risk PRS associated with IPF diagnosis, OR 2.88 (95%CI 2.41-3.44) compared to all other individuals. A high-risk PRS also associated with the composite endpoint of mortality or lung transplant among those with an IPF diagnosis, HR 1.23(95%CI 1.11-1.35) compared to all other individuals. Conclusions A PRS can identify those at risk for an IPF diagnosis and mortality in biobank-scale data, which may have implications for clinical decisions. Further work is necessary to evaluate the utility of adding genetics in clinical settings.

Emerging evidence links veno-venous extracorporeal membrane oxygenation (VV-ECMO) to right ventricular (RV) dysfunction, but the relative contribution of ECMO versus underlying disease progression remains unclear. We conducted a multicenter, retrospective, propensity-matched study including 408 intubated acute respiratory distress syndrome (ARDS) patients who were admitted between January 2020 and October 2024 in a quaternary referral hospital network within the United States and underwent at least two transthoracic echocardiograms (TTEs) after intubation. Using 1:2 propensity score matching, we adjusted for baseline comorbidities, baseline hemoglobin, lactate, and worst PaO 2 /FiO 2 ratio (P/F). Longitudinal echocardiographic changes were analyzed with a cumulative link mixed model (CLMM), evaluating RV size and function as ordinal outcomes. Within 408 patients (112 received ECMO support), propensity matching identified 55 ECMO and 110 non-ECMO patients with balanced baseline characteristics. Among 469 serial echocardiograms, RV size and function worsened more frequently in ECMO patients. In longitudinal modeling, ECMO use alone was not associated with RV dilation ( p = 0.23) or dysfunction ( p = 0.43). However, longer ECMO duration was associated with RV dilation (OR: 1.04 per day, p = 0.004) and dysfunction (odds ratio [OR]: 1.04 per day, p < 0.001). Higher ECMO circuit flow had a trend toward progressive RV dilation and dysfunction but did not reach statistical significance. These findings highlight the need for vigilant RV monitoring during ECMO support.

Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Background: Smokers with multiple sclerosis (MS) experience worse disease, yet underlying mechanisms remain unknown. Smoking disrupts bile acid and tryptophan metabolism in non-MS populations; both pathways involve host–microbiome co-metabolism and have been linked to MS. Objective: Determine whether smoking perturbs these metabolic pathways in MS and whether such alterations statistically mediate smoking’s effect on MS severity. Methods: We analyzed serum bile acid, tryptophan, and tobacco-related metabolites across four independent MS cohorts ( N = 266) using discovery-replication analyses. Mixed-effects regression assessed replicating associations with current smoking and nicotine exposure. Mediation analyses tested if replicating metabolites were potential mediators between smoking and MS severity. Hypothesis-generating metagenomic analyses explored smoking-associated gut–microbial shifts and metabolite correlations. Results: Current smokers and nicotine-exposed MS subjects had reductions in bile acids and tryptophan metabolites, notably indolepropionate, a neuroprotective, anti-inflammatory gut–microbial metabolite. Lower indolepropionate statistically mediated ~20% of smoking’s adverse effect on MS severity. Metagenomic analyses identified potential smoking-enriched MS-linked taxa, and that indolepropionate broadly co-occurs with microbial networks (e.g. Lachnoclostridium appeared inversely associated with indolepropionate in smokers with MS). Conclusion: Tobacco exposure disrupts host–microbiome tryptophan and bile acid metabolism in persons with multiple sclerosis, with indolepropionate depletion partially mediating disease severity, highlighting a potential mechanistic pathway warranting further investigation in MS smokers.