Citations

Abstract Background Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD. Methods Participants with IBD (ulcerative colitis [UC], Crohn’s disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months. Results Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively). Conclusions The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.

Abstract Background We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn’s disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content. Methods Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested. Results Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = −0.39 [95% confidence interval {CI}: −0.61, −0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P < .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = −.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = −.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13). Conclusions Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.

Abstract Electroconvulsive therapy (ECT) is an effective treatment for severe depression, especially in treatment-resistant cases. However, its potential cognitive side effects necessitate careful dosing to balance therapeutic benefits and cognitive stability. Recent advances in electric field (E-field) modeling offer promising avenues to optimize ECT dosing. This review synthesizes current knowledge on E-field modeling in ECT and explores its clinical applications. It examines the variability in E-field strengths and distributions induced by ECT and their impact on clinical outcomes. Additionally, the relationship between E-field strengths, neuroplasticity, and therapeutic efficacy is discussed. Translational studies of E-field-informed ECT are highlighted, emphasizing individualized optimal amplitude dosing and potential clinical applications. This review provides useful insights into how E-field modeling can improve the effectiveness of ECT while minimizing adverse effects, helping guide future research and clinical practice.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS Sixty-one studies form the evidence base. RECOMMENDATIONS Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration–approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care. Additional information is available at www.asco.org/gynecologic-cancer-guidelines . This guideline has been endorsed by the Society of Gynecologic Oncology.

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Abstract Background Risankizumab (RZB), a high-affinity humanised IgG1 monoclonal antibody targeting interleukin-23 p19, has shown sustained efficacy and an acceptable safety profile for patients (pts) with ulcerative colitis (UC).1 This interim analysis reports efficacy data at week (wk) 0 and wk 96, as well as safety data of the COMMAND (NCT03398135) open-label extension (OLE). Methods The COMMAND OLE enrolled pts who completed 52-wks maintenance dosing in the COMMAND substudies or entered directly from the induction study.1 All pts received RZB180 subcutaneous (SC) starting at OLE wk 0, except pts who had prior rescue therapy (single RZB 1200 mg intravenous [IV] dose then RZB360 Q8w) who continued RZB360 in the OLE. The OLE was not designed to compare RZB180 and RZB360 groups. The data cut-off date for this interim analysis was as of June 30, 2024. Efficacy endpoints assessed were clinical remission (CR) per AMS, clinical response per AMS, endoscopic improvement, endoscopic remission, and corticosteroid-free CR per Partial AMS up to wk 96. Data are reported as observed prior to RZB rescue therapy during OLE. The safety analysis also includes pts who directly entered the OLE from induction; presented as events/100 pt years (E/100 PY). Results Of the pts who entered the OLE (RZB180, N = 701; RZB360, N = 302), approximately 40% of pts had the opportunity to reach OLE wk 96 as of the cut-off date. At OLE wk 0 and 96, a similar proportion of patients in the RZB180 group achieved clinical and endoscopic outcomes (Figure 1A). In the RZB360 group, the percent of pts achieving clinical and endoscopic endpoints increased from OLE wk 0 through OLE wk 96 (Figure 1B). Similar rates of serious AEs, severe AEs, and AEs leading to discontinuation of study drug were reported in the RZB180 group and the RZB360 group with no new safety risks identified (Table 1). Conclusion In this interim analysis of the OLE, a sustained benefit was observed with long-term RZB treatment up to 96 wks. The long-term safety profile for RZB remains consistent and supports the long-term use. References 1. Louis E et al. JAMA 2024;332(11):881-897

Purpose To compare the surgical outcomes of anterior cruciate ligament (ACL) reconstruction using hamstring autograft (HA) plus lateral extra‐articular tenodesis (LET), isolated all‐soft tissue quadriceps autograft (QA), and isolated HA. Methods A retrospective review was performed comparing high‐risk patients undergoing ACL reconstruction with isolated HA, isolated QA, or HA + LET from August 2013 to January 2023. High‐risk patients, as determined by high‐grade pivot shift or generalized ligament laxity, with at least a 2‐year follow‐up, were included. Lysholm and International Knee Documentation Committee scores were compared at 3, 6, 12, and 24 months postoperatively. Retear rate, postoperative pivot‐shift grade, return to sport, and complications were recorded. Results In total, 159 patients (56 HA, 47 HA + LET, and 56 QA) were included. At 6 months postoperatively, the HA International Knee Documentation Committee score was significantly lower than that of the HA + LET and QA groups ( P < .0001). Similarly, the Lysholm score was significantly lower in the HA cohort at 6 months, 1 year, and 2 years postoperatively ( P < .0001‐.02). There was no difference in the rate of achieving the minimally important clinical difference between the cohorts for either of these outcome scores. The retear rate was significantly higher in the HA group (17.9%) compared to the HA + LET (4.3%) and QA (1.8%) cohorts ( P = .01). The rate of postoperative pivot shift of grade 2 or more was also higher in the isolated HA group ( P = .04). Conclusions The use of an all‐soft tissue QA or HA + LET for ACL reconstruction resulted in a lower retear rate and postoperative pivot‐shift grade compared to an isolated HA graft in high‐risk patients at 2 years postoperatively. There was no difference in the rate of achieving the minimal clinically important difference between the cohorts. The QA and HA + LET reconstruction options may improve stability and decrease the failure rate compared with HA reconstruction alone. Level of Evidence Level III, retrospective cohort study.

Cases: Two patients with spontaneous loss of thumb interphalangeal joint extension were referred after history, electrodiagnostic, and/or magnetic resonance imaging (MRI) findings were felt to demonstrate a posterior interosseous nerve (PIN) palsy. Subsequent physical examination and additional directed studies suggested an alternative explanation: rupture of the extensor pollicis longus (EPL) tendon, subsequently confirmed at surgery. An extensor indicis proprius to EPL transfer restored thumb function. Conclusion: Electrodiagnostic and MRI changes consistent with diffuse PIN palsy may occur in the setting of EPL rupture. An accurate diagnosis of EPL dysfunction requires careful physical examination and confirmatory imaging. Further study of this previously unreported phenomenon is required.