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ABSTRACT Background Cardiac amyloidosis (CA) is frequently complicated by atrial fibrillation (AF), yet outcomes after left atrial appendage occlusion (LAAO) in this population remain poorly defined. Methods We conducted a retrospective TriNetX study of adults with AF undergoing LAAO, comparing patients with and without CA after 1:1 propensity matching. Outcomes were assessed using Kaplan–Meier analyses and Cox regression. Results Among 532 matched pairs, mortality and major adverse cardiovascular events were similar between groups, whereas major bleeding was higher in CA (HR 1.90). Conclusions LAAO yields comparable ischemic outcomes in CA, though bleeding risk is increased.

Background Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC. Methods Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once daily, or 150 mg once daily) and then BMS-813160+chemotherapy (gemcitabine+nab-paclitaxel (gem/nabP; 1L PDAC), 5-fluorouracil+leucovorin+irinotecan (FOLFIRI; 1L CRC)), or nivolumab (2/3L MSS CRC). Part 2 included patients with metastatic 1L PDAC or 2L CRC. Patients received BMS-813160 300 mg two times a day+gem/nabP±nivolumab (1L PDAC), BMS-813160 300 mg two times a day or 150 mg once daily+FOLFIRI (2L CRC), or chemotherapy alone. Primary endpoints were safety and pharmacodynamics (Part 1) and efficacy (Part 2). Results In Part 1, 22 of 75 (29%) and 54 of 72 (72%) patients experienced a treatment-related adverse event during monotherapy lead-in and overall, respectively. Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred. In Part 2, patients with 1L PDAC who received BMS-813160 300 mg two times a day+gem/nabP+nivolumab achieved an overall response rate (ORR) of 37% (13/35); the median duration of response (DOR) was 45 weeks (95% CI 26.1 to not evaluable). ORRs with BMS-813160 300 mg two times a day+gem/nabP and gem/nabP alone were 26% (9/35) and 28% (9/32), respectively; median DORs were 121 and 31 weeks, respectively. Progression-free survival rates at 24 weeks were 56% (BMS-813160 300 mg two times a day+gem/nabP+nivolumab), 56% (BMS-813160 300 mg two times a day+gem/nabP), and 50% (gem/nabP). ORRs in 2L CRC were 19% (6/32; BMS-813160 300 mg two times a day+FOLFIRI), 13% (4/32; BMS-813160 150 mg once daily+FOLFIRI), and 27% (7/26; FOLFIRI). Conclusions In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated. Trial registration number NCT03184870 .

OBJECTIVE The objective of this study was to describe the long-term efficacy of single-fraction stereotactic radiosurgery (SRS) for the primary treatment of sporadic vestibular schwannoma. METHODS Adult (≥ 18 years of age) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients met inclusion criteria, the majority (n = 566, 76%) of whom had tumors extending into the cerebellopontine angle at SRS. The median patient age at SRS was 62 years, half (50%) of the patients were women, and 744 (99%) exhibited House-Brackmann grade I facial nerve function at SRS. A total of 42 patients experienced radiosurgical failure and underwent salvage treatment; the median duration of follow-up for the patients who did not undergo salvage treatment was 7.0 years. Overall tumor control rates (95% CI, number still at risk) at 1, 3, 5, 10, and 15 years after SRS were 100% (100%–100%, 718), 98% (97%–99%, 589), 96% (94%–97%, 464), 92% (90%–95%, 258), and 91% (89%–94%, 125), respectively. Patient age (hazard ratio [HR] for a 10-year increase of 0.92, 95% CI 0.71–1.19; p = 0.5), presence of a macrocystic tumor (HR 0.59, 95% CI 0.14–2.46; p = 0.5), and treated tumor volume (HR for a 1-cm 3 increase of 1.02, 95% CI 0.88–1.18; p = 0.8) were not significantly associated with the risk of salvage. Three distinct post-SRS tumor behavior patterns were observed, with 13% of patients demonstrating tumor pseudoprogression, all but 4 of whom demonstrated pseudoprogression by year 5 post-SRS. CONCLUSIONS SRS demonstrates durable tumor control through 15 years of follow-up in most patients (91%); however, a minority are found to still experience SRS failure even beyond 10 years of surveillance. Although occurring in only a minority of patients, tumor pseudoprogression can be evident out to 5 years or longer post-SRS.

OBJECTIVE Wait-and-scan surveillance is now commonly employed for initial management of small- and medium-sized vestibular schwannomas. Although small differences in tumor size are unlikely to impact outcomes significantly, treatment with either radiosurgery or microsurgery is usually recommended following radiological detection of tumor growth. The objective of the current study was to identify potential inflection points in vestibular schwannoma tumor size, where the risks of treatment with single-fraction stereotactic radiosurgery (SRS) accelerate to inform timing of intervention. METHODS Adult (≥ 18 years old) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients with a median age at SRS of 62 years were studied, the majority (n = 566 [76%]) of whom had tumors extending into the cerebellopontine angle (CPA) at SRS. The optimal tumor size cut point to predict SRS failure and need for salvage treatment was 4 mm or more of CPA extension (c-index 0.59, HR 3.60, p = 0.01). The optimal tumor size cut point to predict the outcome of facial nerve paresis was 13 mm or more of CPA extension, resulting in a c-index of 0.63 (HR 2.88, p = 0.01). Among patients with at least 3 months of surveillance before SRS, those with a tumor growth rate ≥ 2.5 mm/year were more likely to undergo salvage treatment than those with a growth rate < 2.5 mm/year, although this difference did not achieve statistical significance (HR 1.82, p = 0.18). CONCLUSIONS The risk of SRS failure requiring salvage treatment and the risk of post-SRS facial nerve paralysis increase at sizes of approximately 4 and 13 mm extension into the CPA, respectively, providing a size threshold anchor to help guide treatment decision-making regarding timing of SRS. Furthermore, rapid tumor growth during the initial wait-and-scan period may be associated with an increased risk of radiosurgical failure, which may influence choice of treatment.

OBJECTIVE Core outcome sets (COSs) are needed to promote data consistency across studies as well as data synthesis and comparability. The aim of the current study was to use a modified Delphi process to develop a COS for lateral femoral cutaneous neuropathy (LFCN), hereafter COS-LFCN. METHODS A 5-stage approach was used to develop the COS-LFCN: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. This study followed the Core Outcome Set - STAndards for Development, (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 25 participants, all neurological surgeons, representing 14 countries. The final COS-LFCN consisted of 41 factors and outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS for LFCN and provided definitions, methods of implementation, and time points for assessment. The COS-LFCN should serve as the minimum data to be collected in all future neurosurgical studies on LFCN. Incorporation of this COS will help improve consistency in reporting, data synthesis and comparability, and minimize outcome reporting bias.

OBJECTIVE The aim of this study was to determine predictors of the minimum clinically important difference (MCID) in the Neck Disability Index (NDI) following cervical spinal deformity surgery. METHODS A retrospective review was performed of a prospective, multicenter adult cervical spinal deformity database. All patients had baseline and 1-year NDI scores. Patients met MCID with an improvement of NDI by 7 points between baseline and 1 year, as previously established. Baseline demographics, comorbidities, and both baseline and 1-year spinopelvic parameters were evaluated for statistical significance in a univariate logistic regression analysis. Significant variables, in addition to baseline NDI, were analyzed in a multivariable logistic regression model by backward selection with Akaike information criterion minimization. RESULTS A total of 122 patients were included with a median age of 62 (IQR 56, 69) years; 62% of patients were female. Of the 122 patients, 72 (59%) achieved NDI MCID at 1 year. Predictors of achieving MCID on univariate analysis included a lower Charlson Comorbidity Index (CCI) total score (OR 0.70, p = 0.03), depression as a comorbidity (OR 2.9, p = 0.02), lower C2 tilt at the 1-year follow-up (OR 0.92, p = 0.02), and a greater difference between 1-year postoperative C2–7 sagittal vertical axis (SVA) and preoperative C2–7 SVA (OR 0.98, p = 0.0495). On multivariable logistic regression analysis, predictors of achieving MCID included a lower CCI (OR 0.62, p = 0.03), depression as a comorbidity (OR 3.1, p = 0.059), a greater change in C2–7 SVA at the 1-year follow-up compared with baseline (OR 0.97, p = 0.055), and baseline NDI (OR 1.02, p = 0.24) with an area under the curve of 0.74. CONCLUSIONS The best-fit multivariable model included higher baseline NDI, a greater change in C2–7 SVA, patient-reported baseline depression, and lower CCI as important factors in predicting NDI MCID.

OBJECTIVE This study aimed to determine minimum clinically important difference (MCID) values for dysphagia using the Eating Assessment Tool-10 (EAT-10) in patients undergoing anterior cervical surgery, focusing on early dissatisfaction and later satisfaction thresholds to guide clinical decisions. METHODS Data were prospectively collected from patients undergoing anterior cervical surgery across three institutions from 2016 to 2024. Dysphagia severity was assessed preoperatively and at various postoperative stages up to 1 year using EAT-10. The inverse probability of treatment weighting was used to control for confounding variables. The retrospective study of patient data employed two analytical phases: the first phase examined the relationship between dissatisfaction at 3 months (indicated by a North American Spine Society satisfaction score > 2) and changes in EAT-10 scores from baseline to peak (i.e., worst) postoperative scores; the second phase focused on recovery, comparing changes in EAT-10 scores from peak postoperative scores to 12 months against satisfaction (score < 2) at 12 months. RESULTS The mean ± SD baseline EAT-10 score for the 1463 patients included in the study was 1.5 ± 4.7 and the mean peak score was 5.2 ± 7.4. The patients underwent anterior cervical discectomy and fusion (90%), arthroplasty (6%), or corpectomy (4%); a hybrid procedure was used in 1%. The phase 1 analysis indicated that a 4-point increase in EAT-10 score was a threshold for significant postoperative dissatisfaction in those without baseline dysphagia, with much higher thresholds observed in patients with any baseline dysphagia. In phase 2, among patients with baseline EAT-10 scores < 3 who experienced an increase to EAT-10 score ≥ 8 postoperatively, a subsequent decrease of 9 points by 12 months was necessary to report satisfaction. For patients with baseline scores 3–8 whose postoperative scores rose to ≥ 8, a subsequent decrease of 15 points was necessary for satisfaction. Patients with initial scores of ≥ 8 who did not improve to < 3 immediately after surgery required further reductions of 2–11 points to reach satisfaction. CONCLUSIONS The MCID thresholds from this study provide crucial benchmarks for assessing dysphagia changes after anterior cervical surgery, allowing tailored interventions. Patients with baseline dysphagia are less likely to experience early dissatisfaction, and high peak scores negatively impact long-term satisfaction. These findings emphasize the importance of proactive dysphagia management to enhance patient outcomes.

Abstract Background The STOMP2 trial sought to determine whether the implantable autologous cell therapy AVB-114 is an effective add-on therapy for patients with persistent Crohn’s perianal fistulas. The trial design incorporated wait-list controlled (WLC) elements, allowing eligible control group subjects who completed the 9 mo primary endpoint visit in Part 1 to request AVB-114 treatment in Part 2 and strengthen the evaluation of AVB-114’s safety and effectiveness. Methods Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional Crohn’s disease therapy. Subjects at 14 U.S. sites were randomized 1:1 to either standard of care (SoC; fistula optimization including seton placement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 9 mo, defined as no collections &gt;2cm on MRI, visual closure of the external opening, and no drainage of fluid despite gentle finger compression. A logistic regression time from exposure model through 9 mo utilized complete Part 1 data and all available Part 2 data to estimate combined AVB-114 effectiveness. Results Part 1 combined remission (using Non-Responder Imputation) was 8.3% (2/24) for SoC and 45.8% (11/24) for AVB-114 (38% difference, 95% CI 11 – 60%, post-hoc p-value of 0.0078). Twenty SoC subjects were treated with AVB-114 in Part 2. Four of the 9 Part 2 subjects with 9 mo combined remission data available were in combined fistula remission (44.4%). No subjects failed 9 mo radiological remission (first component of the primary endpoint), thus clinical remission (composite of the latter two components) was equivalent to combined remission. AVB-114 clinical remission in Part 1 and Part 2 to-date were similar, and when combined provided narrower estimates with the same coverage (Figure 1). Mean (SD) 9 mo perianal disease activity index (PDAI) scores for SoC, Part 1 AVB-114, and Part 2 AVB-114 were 5.0 (2.6), 4.1 (2.9), and 3.8 (3.5), respectively. Lower 9 mo scores and decreases from baseline were independently associated with an increased probability of clinical remission. Two serious treatment-emergent adverse events (TEAEs; pseudopolyposis and proctalgia) occurred, with the latter attributed to AVB-114. Non-serious product related TEAE were predominantly related to postoperative perianal pain. Two grade 2 (moderate) AEs of cellulitis and abdominal wall abscess were attributed to adipose tissue collection. Conclusion Both the randomized and combined (all-treated) analyses demonstrated substantial AVB-114 effectiveness through 9 mo in this challenging patient population. AEs were anticipated, and generally mild and infrequent. Conflict of interest: Schwartz, David: 1) Abbvie: consultant 2) Janssen: Consultant 3) Takeda: Consultant 4) Avbios- consultant 5) Olympus- consultant Dozois, Eric: TBD Ehman, Eric: TBD Faubion, William: TBD Hudesman, David: Consultant: Avalo, Abbvie, Abivax, Biocon, BMS, CorEvitas, Eli Lilly, Johnson and Johnson, Pfizer, Prometheus, Sanofi, Takeda, Fresenius Kabi Research Support: Pfizer and Johnson and Johnson Espen, Benjamin: employee of Avobis Bio LLC Pabla, Baldeep: Astellas, J & J - Advisory Board Prometheus - Speaker Eli Lilly - Speaker Papadakis, Konstantinos: TBD

Background. Acute cellular rejection (ACR) remains a major cause of morbidity after heart transplantation despite advances in immunosuppression. Whole genome transcriptomic profiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive, longitudinal biomarker assessments capable of capturing the temporal dynamics of rejection biology remain scarce. Methods. RNA sequencing of peripheral blood from heart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assess gene-based prediction of ACR. Results. A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning–based classifier, DYNLL1 and SERF2 were identified as ACR predictive genes, and achieved a cross-validated area under the receiver operating characteristic curve of 0.63. Conclusions. Peripheral blood transcriptomics identify dynamic temporal responses in ACR including T- and B-cell pathways with potential ACR predictive genes that warrant further investigation.