Citations

Abstract The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post–CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy (22 patients; overall response rate [ORR], 40%), pirtobrutinib (17 patients; ORR, 36%), and bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (<3 vs 3-6 vs >6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.

Objectives To examine associations between multimorbidity, the social determinants of health (SDoHs) and rheumatoid arthritis (RA) flare and remission. Methods All patients aged ≥18 years in Olmsted County, Minnesota, with incident RA in 1999–2014 were identified. Using a list of 55 chronic medical conditions, multimorbidity was defined as the presence of ≥2 conditions and substantial multimorbidity as ≥5 conditions. The Area Deprivation Index and Social Vulnerability Index (SVI) were used as proxies for adverse SDoH burden. Flare and remission were defined using Outcome Measures in Rheumatoid Arthritis Clinical Trials definitions. Mixed effects models were used to assess associations between flare/remission and multimorbidity, adverse SDoH burden and other patient characteristics. Results This study included 659 patients with incident RA. Multimorbidity and substantial multimorbidity predicted 29% (OR:1.29, 95% CI:1.04 to 1.59) and 26% (OR:1.26, 95% CI:1.03 to 1.53) higher odds of flare, respectively. Both were associated with 34% (OR:0.66, 95% CI:0.49 to 0.90) and 33% (OR:0.67, 95% CI:0.51 to 0.90) lower odds of remission, respectively. SVI predicted 8% lower odds of remission for every 0.1 increase above 0.3 (OR:0.92, 95% CI:0.85 to 0.99). Flare was also associated with female sex, smoking, younger age and shorter disease duration, but not seropositivity. Remission was also associated with male sex, never smoking, older age and longer disease duration, but not seropositivity. Conclusions Multimorbidity predicts higher odds of RA flare and lower odds of remission. Adverse SDoH burden predicts lower odds of remission. These findings have the potential to inform disease prognostication and clinician interventions.

The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel’s recommendations for overall management of both favorable histology WT and anaplastic WT.

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term “adenocarcinoma” should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with “glandular differentiation” because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Menstrual irregularities and abnormal uterine bleeding have been increasingly reported following severe acute respiratory syndrome coronavirus 2 infection, likely due to viral-induced endocrine disruption and immune dysregulation. A woman in her late 30s, with previously regular menses, developed persistent abnormal uterine bleeding after recovering from coronavirus disease 2019. Lab work-up over the next 2 years demonstrated high follicle-stimulating hormone, low anti-Müllerian hormone, low estrogen, and borderline antinuclear antibody titers. A pelvic ultrasound showed low antral follicle count, and she had challenges with fertility preservation. The patient was suspected of having an exaggerated immune reaction to severe acute respiratory syndrome coronavirus 2 infection with her strong family history of autoimmune disease and borderline antinuclear antibody, which may have led to an autoimmune-induced premature ovarian insufficiency. This case highlights the need to recognize post-viral menstrual irregularities and endocrine dysfunction as a potential consequence of coronavirus disease 2019. Clinicians should consider postinfectious endocrine disturbances in patients with new-onset abnormal uterine bleeding or infertility and evaluate for immune-mediated mechanisms when appropriate. Further research is needed to elucidate the long-term impact of coronavirus disease 2019 on reproductive health.

Abstract Postoperative pain control after total knee arthroplasty (TKA) remains challenging, particularly in patients utilizing chronic opioids preoperatively. Our study aimed to evaluate the effect of regional nerve blockade on perioperative pain control outcomes after TKA in patients using or not using chronic preoperative opioids. A retrospective review of our institutional database identified 434 chronic opioid patients defined as documented ongoing use greater than 3 months prior to contemporary TKA. Patients were 1:1 matched to nonopioid users based upon age, sex, body mass index, and regional block type (single-shot adductor canal block [ACB, 29%], 3-day ACB catheter [31%], or no block [41%]). All patients underwent primary TKA using periarticular injections and contemporary multimodal pain management. Immediate and 90-day postoperative outcomes, including Knee Osteoarthritis Outcome Score, Junior (KOOS, Jr), were compared via univariate analysis among the matched cohort and regional block type among chronic opioid patients. Chronic opioid patients demonstrated higher inpatient opioid use than controls (90 vs. 65 oral morphine equivalents [OMEs], respectively, p < 0.01), but no significant differences existed in length of stay (LOS), discharge pain scores, 90-day readmission or KOOS, Jr (all p ≥ 0.05). When comparing chronic opioid patients according to block type, those receiving no block had the highest LOS (1.6 days, p < 0.01), discharge pain score (5.0, p < 0.01), and inpatient opioid use (80 OMEs, p < 0.01) compared with either ACB. The subgroup receiving an ACB catheter demonstrated a significantly higher 90-day readmission rate (9%, p < 0.05). Patients utilizing chronic opioids preoperatively require more opioids in the immediate postoperative period after TKA compared with nonopioid users despite contemporary modalities. Nonetheless, the use of any type of ACB provides improved pain control in these patients.

INTRODUCTION: Treatment of celiac disease (CeD) requires a strict gluten-free diet (GFD). Adherence is difficult to assess and influenced by many factors. Identification of potential gluten exposures is essential, but no validated screening measures exist in pediatrics. The aim of this study was to develop and validate a measure screening for gluten exposure risk in pediatric patients with CeD. METHODS: The Gluten Exposure Risk Assessment (GERA) was developed in 3 phases. First, items were generated and refined by a modified Delphi process. Next, psychometrics, factor structure, and validity were examined in a sample of caregivers of pediatric patients younger than 18 years with CeD at 12 pediatric celiac centers. Finally, the final measure was tested on an independent sample population using confirmatory factor analysis and test-retest data. RESULTS: A total of 134 items were generated representing up to 6 domains, with 36 items selected for initial testing. Based on psychometrics and confirmatory factor analysis data from 484 caregivers, the final measure included a total of a single screening question and 9 validated items representing 2 domains (Home, Outside). Repeat testing on a separate sample (N = 369) confirmed factor structure and validity of the final measure (Comparative Fit Index = 0.96, Tucker–Lewis index = 0.95, root mean square error of approximation = 0.06). DISCUSSION: The GERA is a valid screening measure, completed by caregivers, for assessment of gluten exposure in children and adolescents with CeD following a GFD. GERA is a useful tool for evaluating the potential of risk of gluten exposure and potential need for intervention.

Clonus is a disabling symptom of upper motor neuron dysfunction in patients with multiple sclerosis (MS). We report immediate termination of mechanically evoked clonus by epidural lumbosacral spinal cord stimulation (ES) in a 58-year-old man with secondary progressive MS. This observation was captured during training using video and skin surface electromyography of soleus muscle activity. ES immediately reduced mechanically evoked clonus duration and cycle count compared to trials without stimulation, as determined by a Kruskal–Wallis test ( p < 0.05, n = 2–3 trials), and reverted to baseline status when stimulation was off.