Citations

ABSTRACT Background Minimal‐invasive surgery (MIS) was proven beneficial in Crohn's Disease (CD). Intracorporeal anastomosis (ICA) represents a further improvement as it is associated with decreased complications and shorter hospitalization. Extracorporeal anastomosis (ECA) is preferred to ICA as it allows haptic feedback of the bowel and mesentery, which is historically required for bowel resection in CD to minimize recurrences. We compared ICA and ECA in terms of recurrences and complications. Methods All patients between 2016 and 2022 with Crohn's disease who underwent a MIS ileocecectomy were identified and divided into ICA and ECA groups. Exclusion criteria were open surgery, end ileostomies, follow‐up < 1 month, and ileocecectomy not due to CD. Results 107 patients were included in the ICA group (44.9% male, mean age of 40.2 [±16.6] years), while 270 patients were in the ECA group (46.7% male, mean age of 41.9 [±17.3] years). The rate of endoscopic recurrences with a Rutgeerts score > 2, clinical recurrence, and surgical recurrence were not statistically different between the two cohorts. On the multivariable analysis for endoscopic and clinical recurrences, the ICA/ECA approach was not significant. The ECA group revealed a higher overall complication rate (30.4% versus 15.9%, p = 0.004). The median length of stay was significantly reduced in the ICA group ( p < 0.001). Conclusion ICA seems to be safe in ileocecectomies for CD. The complication rate and length of stay were reduced while not affecting the endoscopic, clinical, and surgical recurrence rates. MIS technology provides enhanced visualization and haptic feedback, which could be used as surrogates for the tactile evaluation intra‐operatively.

OBJECTIVE The aim of this study was to elucidate the long-term morbidity associated with untreated cerebral cavernous malformation (CCM). METHODS From a prospectively maintained database of patients with CCM, we assessed functional outcome as measured using the modified Rankin Scale (mRS) score at baseline and the last untreated follow-up evaluation. Disability was defined as an mRS score ≥ 3. Kaplan-Meier curves were used to assess the time to disability, and Cox proportional hazards models were used to determine risk factors for disability. Furthermore, the predictive performance of a previously published nomogram for morbidity in CCM was assessed. RESULTS The cohort consisted of 332 patients (58.4% female, mean age at diagnosis 44.5 years), with 19.8% having the familial form and 28.0% having a CCM located in the brainstem. Of 48 patients who presented with symptomatic hemorrhage (SH) and who did not undergo surgery or have a prospective SH, 27.1% had an mRS score ≥ 3 at diagnosis. By 1 year and 5 years, this improved to 6.2% and 4.7%, respectively. Over a mean follow-up duration of 6.6 years, 103 of 332 patients (31.0%) had one prospective SH and 48 (14.5%) had multiple prospective SHs. Patients with brainstem-located CCM had an 18.8% 5-year and 35.4% 10-year risk of disability compared with 4.1% and 7.5%, respectively, in patients with a nonbrainstem location (p < 0.0001). Multivariate analysis showed that a brainstem location, history of self-reported psychiatric disorder, and ≥ 2 SHs were predictive of disability at the last follow-up. External validation of a published nomogram demonstrated high specificity but limited sensitivity for predicting disability, with an area under the receiver operating curve of 0.687 for mRS scores ≥ 2 and 0.783 for mRS scores ≥ 3. CONCLUSIONS Most patients improved after a first hemorrhage, with the most improvement occurring in year 1. Disability increased with each SH. Disability was associated with 2 or more SHs, a brainstem location, and a self-reported psychiatric diagnosis. Ten-year disability risk with a nonbrainstem CCM location was < 8%.

OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy has become a popular tool in the neurosurgical armamentarium for managing tremor in patients with essential tremor (ET) and Parkinson’s disease (PD). METHODS Given the recent exponential growth in the use of this technology, the American Society for Stereotactic and Functional Neurosurgery, which acts as the joint section representing the field of stereotactic and functional neurosurgery on behalf of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, provides an update on treatment indications and the efficacy and safety of MRgFUS for the treatment of tremor. RESULTS In ET, the efficacy of MRgFUS thalamotomy is supported by several open-label and 1 prospective, double-blind, sham-controlled randomized clinical trial (RCT) that showed a 47% improvement in hand tremor in the short term. Follow-up studies demonstrated that the benefits of MRgFUS for ET are sustained in the long term. Studies investigating the effects of bilateral staged MRgFUS thalamotomy in patients with ET have shown that tremor improvement on the second side was as significant as that observed after the first procedure. The efficacy of MRgFUS thalamotomy for PD tremor is supported by a systematic meta-analysis that consisted predominantly of smaller, nonrandomized studies; 1 RCT; and 1 prospective cohort study. Despite a significant short-term improvement in PD tremor, the long-term effects of this therapy remain unknown. Common early adverse effects of MRgFUS thalamotomy include gait disturbance and paresthesias. These, however, tend to subside over time. Other reported side effects are dysarthria, ataxia, taste disturbance, motor deficits, and speech difficulty. CONCLUSIONS MRgFUS thalamotomy is a safe, effective, and durable intervention for refractory ET in appropriately selected patients. The procedure appears to be safe and effective for PD tremor, although the long-term durability of the technique remains a concern. Early experience with bilateral staged lesions for ET suggests the procedure to be safe and effective.

Background/Objective: Dietary, supplement, and activity exposures have only been studied in spondyloarthritis (SpA) with retrospective studies. We aimed to determine the association of diet, supplements, and physical activity with incident SpA. Patients and Methods: We performed a case-control study in the Mayo Clinic Biobank from 2009 through 2015, matching criteria-confirmed incident SpA cases to controls 1:5 on age, sex, recruitment year, and location. Questionnaires assessed 16 dietary, 29 supplement, and leisure-time/work activity exposures. Logistic regression models calculated adjusted odds ratios (aOR) with 95% CIs of SpA for each exposure, adjusting for covariates. Sensitivity analyses were conducted within HLA-B27-positive patients, and those with baseline questionnaires completed 5+ years before index. Results: We identified 73 cases of incident SpA matched with 365 controls (mean age: 60, 70% females). No dietary or activity exposures were associated with SpA overall. However, among HLA-B27-positive individuals, non-diet soft drink consumption was associated with increased risk of SpA (aOR: 4.82, 95% CI: 1.29-18.1), whereas caffeinated coffee was associated with decreased risk (aOR: 0.20, 95% CI: 0.04-0.89). Zinc was associated with increased risk of SpA (aOR: 4.16, 95% CI: 1.19-14.6), as were B vitamins in the HLA-B27-positive subgroup (aOR: 4.21, 95% CI: 1.04-17.1). In the 5-year sensitivity analysis, low leisure-time physical activity plus high work physical activity was associated with increased risk of SpA (relative excess risk due to interaction: 0.50, 95% CI: 0.03-0.98). Conclusions: Due to small sample size and multiple comparisons, the risk factors we identified (non-diet soft drinks, B vitamins, and zinc) should be considered hypothesis-generating and warrant further investigation.

Abstract Increased absolute lymphocyte count (ALC) may predict risk of treatment-related mortality and atypical neurologic events among patients receiving chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory multiple myeloma. In this study, we analyzed the clinical outcomes of patients receiving ciltacabtagene autoleucel (cilta-cel) at the Colorado Blood Cancer Institute, from September 2023 to January 2025. Baseline data were collected pre/post-CAR T-cell therapy. Patients were stratified into preintervention (treated September 2023 to July 2024) and intervention (treated August 2024 to January 2025; those with ALC &gt;5 × 103/μL received 3 days of dexamethasone prophylaxis on first identification of elevated ALC). In the preintervention group, 9 of 30 patients had peak ALC &gt;5 × 103/μL; 5 of 9 (55.6%) experienced atypical neurologic events and all 5 died (cilta-cel therapy-related complications). In the intervention group, 7 of 23 patients had peak ALC &gt;5 × 103/μL and received dexamethasone; 1 of 7 had an atypical neurologic event; and 1 death occured (infectious complication, 9 months posttreatment). Dexamethasone prophylaxis in patients with ALC of &gt;5 × 103/μL resulted in rapid ALC reduction. Overall survival (OS) was significantly lower in preintervention patients with ALC of &gt;5 × 103/μL vs intervention patients with ALC of &gt;5 × 103/μL and patients with ALC of ≤5 × 103/μL (P = .0013). ALC &gt;5 × 103/μL (vs ALC ≤ 5 × 103/μL) was significantly associated with atypical neurologic events (odds ratio, 6.8; P = .0157) and lower OS (hazard ratio, 6.2; P = .0106). In conclusion, ALC &gt;5 × 103/μL after cilta-cel treatment predicted severe early neurologic events and high mortality risk. Dexamethasone prophylaxis demonstrated promise for risk mitigation.

Abstract Use of brentuximab vedotin (BV) and PD-1 monoclonal antibodies (mAbs) before autologous stem cell transplantation (ASCT) could impact the benefit of post-ASCT BV maintenance in relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL). We identified 1091 patients with R/R cHL who underwent ASCT between 2010-2022. In total, 244 (22%) received a PD-1 mAb and 443 (41%) received BV before ASCT, while 305 (28%) received BV maintenance. We performed 1:1 propensity score matching to assess the efficacy of BV maintenance in different patient subgroups. Among 608 matched patients, the 3-year progression-free survival (PFS) and overall survival were 73% (95% confidence interval [CI], 70-78) and 95% (95%CI, 93-97), respectively. BV maintenance was associated with improved PFS for patients with no exposure to novel agents, especially those with 2+ modified AETHERA risk factors (0-1 factors: hazard ratio (HR), 0.51; 95%CI, 0.24-1.09; P =.083; 2+ factors: HR, 0.40; 95%CI, 0.25-0.65; P&lt; .001). In contrast, BV maintenance was not associated with a significant PFS benefit for any patient subgroup who received novel agents before ASCT (BV-treated, 0-1: HR, 1.43; 95%CI, 0.53-3.81; P =.48; 2+: HR, 0.79; 95%CI, 0.34-1.82; P =.58; PD-1-treated, 0-1 [P&gt;.99], 2+: HR, 0.25; 95%CI, 0.03-2.14; P =.21). In particular, we observed excellent outcomes for patients undergoing ASCT in a complete response after one line of PD-1-based salvage treatment with no significant benefit for BV maintenance observed (2-year PFS 100% vs 95%; P&gt;.99). The benefit of BV maintenance appears to be attenuated for patients receiving novel agents with salvage therapy. Omission of BV maintenance should be considered for patients anticipated to have excellent outcomes.

Abstract Frontline therapy for systemic amyloid light chain (AL) amyloidosis has evolved significantly with the approval of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone, which has significantly improved rates of both hematologic and organ responses. Despite these advances, many patients eventually relapse, and there remains no established standard salvage regimen or optimal timing. In this review, we examine optimal timing of salvage regimens and currently available therapeutic options after daratumumab failure, including next-generation proteosome inhibitors or immunomodulatory drugs, autologous stem cell transplant, BCL-2 inhibitors, and emerging immunotherapeutic agents such as chimeric antigen receptor T-cell therapy and bispecific antibodies.

Abstract Idecabtagene vicleucel (ide-cel) is a chimeric antigen receptor (CAR) T-cell therapy approved for relapsed and refractory multiple myeloma (RRMM). Out-of-specification (OOS) CAR T cells not meeting criteria for commercial release are considered an investigational product; the expanded access protocol (EAP) allows release of OOS product for administration. The manufacturing analysis of capability, reliability, and timely delivery of ide-cel in the United States over &gt;3 years since its approval included patients with RRMM who underwent leukapheresis for ide-cel treatment after ≥2 prior lines of therapy between 23 February 2021 and 1 November 2024. Additionally, the BB2121-EAP-001 study evaluated safety and efficacy of OOS ide-cel and included patients who had undergone leukapheresis for commercial ide-cel treatment not meeting commercial release specifications, most commonly due to high CD137 activation or low-infused dose. Primary end point was safety. Secondary end points were overall response rate (ORR) and complete response rate (CRR). At data cutoff (1 November 2024), the manufacturing success rate of ide-cel improved from 95.3% in 2021 to 96.8% in 2024. Turnaround time also improved from 31 days in 2021 to 24 days in 2024. In BB2121-EAP-001, 68 (72.3%) patients experienced ≥1 cytokine release syndrome event (mostly grade 1/2) and 15 (16.0%) had neurological toxicities (2 grade 3, 13 grade 1/2). ORR was 75.4% (95% confidence interval [CI], 63.1-85.2), and CRR was 35.4% (95% CI, 23.9-48.2). The manufacturing success of ide-cel is reliable and consistently high, and when OOS ide-cel products emerged, they demonstrated consistent clinical efficacy and safety. The BB2121-EAP-001 study was registered at www.clinicaltrials.gov as NCT04771078.