Citations

Background Mechanical thrombectomy (MT) is established as an effective treatment for large vessel occlusion strokes, but its efficacy and safety for medium vessel occlusions (MeVOs) remain less clear. This study examines the impact of periprocedural embolization to a new vascular territory (ENT) on clinical outcomes in patients with MeVO stroke treated with MT. Methods A multicenter, retrospective analysis was conducted using the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry, including 2122 patients with MeVO stroke w­ho underwent MT between September 2017 and July 2023. ENT was defined as filling defects in previously unaffected territories, excluding embolization near the original occlusion, observed on final angiographic runs after retrieval of the primary thrombus. The associations between ENT, procedural variables, and 90-day clinical outcomes were evaluated, including functional independence (modified Rankin Scale (mRS) scores of 0–2), excellent outcomes (mRS 0–1), mortality, and hemorrhagic complications. Results ENT occurred in 2.9% (63/2122) of patients. Longer onset-to-arterial puncture time (adjusted OR 1.03; 95% CI 1.01 to 1.05; P=0.002) and a greater number of passes (adjusted OR 1.15; 95% CI 1.01 to 1.32; P=0.032) were associated with increased ENT risk, while excellent recanalization (thrombolysis in cerebral infarction (TICI) scale score 2c–3) was associated with reduced ENT risk (adjusted OR 0.41; 95% CI 0.23 to 0.72; P=0.002). ENT was not associated with poorer functional independence, mortality, or hemorrhagic complications. Conclusions ENT during MT for MeVO stroke occurs infrequently and does not significantly affect the clinical outcomes. These findings suggest ENT risk should not deter clinicians from performing MT in patients with MeVO. Further prospective studies are needed to validate these results.

Summary of Background Data: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). Objective: To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. Methods: Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. Results: In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. Conclusion: After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.

Objectives While extracorporeal shockwave therapy (ESWT) may be an efficacious adjunctive treatment option for musculoskeletal injuries, current research is limited by significant heterogeneity within treatment protocols. This study aims to establish international expert consensus recommendations on ESWT terminology, parameters, procedural considerations, contraindications and side effects in the application of ESWT to sports injuries. Methods A systematic literature search was performed on the use of ESWT for musculoskeletal and sports medicine injuries to identify potential panellists, followed by the development of a steering committee-led questionnaire. A three-stage, modified Delphi questionnaire was provided to a panel of 41 international clinical and research experts across 13 countries. Panellists had the opportunity to suggest edits to existing statements or recommend additional statements in Round 1. Consensus was defined as≥75% agreement. Results All 41 panellists completed Rounds 1, 2 and 3. Consensus was reached on 69/118 statements (58.5%), including recommendations on terminology and fundamental concepts, indications for use, procedural aspects for tendinopathy and bone pathologies, treatment correlations with imaging, periprocedural and postprocedural considerations, absolute and relative contraindications and potential side effects. Of the 49 statements that did not reach consensus, 17/49 (34.7%) were related to procedural aspects of bone pathology. Conclusion This international panel presents recommendations on ESWT terminology, indications and treatment considerations to guide ESWT use and decision-making by sports medicine clinicians. While our panel supported the use of ESWT in the treatment of bone pathologies, certain procedural aspects of ESWT specific to these injuries did not reach consensus and require further investigation.

OBJECTIVE The global need for neurosurgical care is significant and often unmet. Building partnerships between high-income countries (HICs) and lower-middle-income countries (LMICs) can help bridge the gap. Six features of sustainable global surgical partnerships have been identified; however, their application in neurosurgery has not been studied. The authors analyzed how the 6 pillars of sustainability are applied to neurosurgical partnerships established by the Neurosurgery Outreach Foundation (NOF) with hospitals in LMICs in Asia. METHODS NOF is an all-volunteer, nonprofit US foundation with the mission to advance neurosurgical care in underserved communities through education, service, and support. The authors examined the NOF programs and identified the characteristics associated with the 6 pillars of sustainability, which are community engagement, multidisciplinary collaboration, education and training, outcome measurement, multisource funding, and bilateral authorship. The authors discuss how these pillars contribute to the establishment of sustainable partnerships. RESULTS From 2010 to 2024, NOF has established partnerships at 4 sites: Cebu, Manila, and Davao, the Philippines; and Ulaanbaatar, Mongolia. Partnerships were established with tertiary or quaternary government hospitals to develop neurosurgical programs tailored to the needs of each site and remained sustained and active. Educational surgical missions were in-person outreach activities conducted annually or biennially and were supplemented with online or remote collaboration. The 5 pillars of sustainable partnerships present at all sites include community engagement, multidisciplinary collaboration, education and training, outcome measurement, and multisource funding. The sixth pillar, bilateral authorship, was present at University of the Philippines–Philippine General Hospital in Manila. CONCLUSIONS Using the 6 pillars of sustainable global partnerships, neurosurgical partnerships can be developed and maintained by all-volunteer nonprofit organizations such as NOF. Incorporating these pillars during the planning and executing of global neurosurgical partnerships are essential for long-term success.

Transcatheter aortic valve replacement (TAVR) was introduced in 2002 and has become integral in the management of aortic stenosis. As an alternative to surgical aortic valve replacement, it relies heavily on safe access to the aortic annulus for implantation of a valve prosthesis. Throughout its development and in current practice, the transfemoral (TF) arterial route for retrograde valve delivery has been the primary approach. However, this route is not appropriate for all patients, which has led to the development of multiple alternate access options. This review discusses the development of access for TAVR, followed by a thorough discussion of TF access. The commercially available products, preprocedural planning, closure techniques, and procedural complications are all discussed. We also describe the various alternate access routes with particular emphasis on the most recently developed route, transcaval access (TCv), with focus on procedural indications, technical considerations, and comparative outcomes. As TAVR technology, indications, and availability all expand, the knowledge and implementation of safe access are of utmost importance.

Abstract The intracluster correlation coefficient (ICC) measures the correlation of observations within clusters and is a key parameter for power and sample size calculations for cluster randomized trials (CRTs). To facilitate the design of future CRTs within the National Cancer Institute Community Oncology Research Program (NCORP), all studies from the NCORP website were reviewed to identify completed CRTs. ICCs for primary and secondary outcomes (when available) were ascertained from these trials and summarized in this article as a resource for future trial development. Although ICCs are relatively small for many outcome cluster combinations, that is not always the case, so consideration should always be given to the specific outcome of interest, trial design, and type of cluster when estimating an ICC to facilitate trial development.

Importance Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D). Objective To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network. Design, Setting, and Participants This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non–GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals’ risks during exposure and nonexposure periods for each drug. The cohort design used propensity score–adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model. Exposures GLP-1RA and non–GLP-1RAs. Main Outcomes and Measures NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific. Results The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum’s deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non–GLP-1RAs using the sensitive NAION definition—empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P &amp;lt; .001). Conclusions and Relevance Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.

537 Background: Translocation renal cell carcinoma (tRCC) is a rare renal cell carcinoma subtype found in about 1-4% of adult patients with RCC and 40% of pediatric RCC cases. Management of advanced tRCC has been guided by clear cell RCC therapy and retrospective reviews which include tRCC cohorts. Novel therapeutic strategies are needed to improve outcomes. This study assessed an individualized neoantigen vaccine with nivolumab plus cabozantinib in a patient with metastatic TFE3-tRCC. Methods: Patient was consented (IRB# 20-011945) for a single-patient investigational new drug (IND#27755). In-house neoantigen prediction bioinformatics pipeline (REAL-neo v2.0) was performed to identify and prioritize neoantigen candidates. Patient underwent lymphodepletion with cyclophosphamide followed by vaccine administration on days 1, 4, 8, 11, 20, 40, week 12, and week 20. Patient was also treated with concurrent nivolumab 480 mg every 4 weeks and cabozantinib 40 mg daily. Objective response rate (ORR) and progression-free survival (PFS) were measured. Results: Patient was diagnosed with TFE3-tRCC and underwent nephrectomy prior to developing metastatic disease. He was treated with multiple liver surgeries, ablations, and radiation therapy without systemic therapy. This controlled his disease for 7 years before he required systemic therapy with ipilimumab plus nivolumab. After 4 cycles, imaging showed progression and was started on cabozantinib which controlled his disease for 1 year. Patient was consented for the neoantigen vaccine. Cycle 1 was administered in April 2022. Three liver lesions and 1 periportal lymph node were monitored. After 4 months of therapy, imaging showed partial response with 34% decrease in sum of target lesions. In June 2023, partial response was ongoing with a 57.4% decrease. A 2 nd vaccine series was administered in June 2023 and had stable disease until progression in June 2024 when patient held his cabozantinib for at least 4 weeks. Neoantigen combination therapy achieved a progression-free survival of 26 months and was well tolerated without significant vaccine-related adverse events. Conclusions: Individualized neoantigen vaccine plus nivolumab and cabozantinib achieved a durable partial response with prolonged progression-free survival. A randomized clinical trial is warranted to further evaluate the efficacy of this combination therapy.

ABSTRACTBackgroundThe factors contributing to sustained ventricular arrhythmias (VAs) >30 days after left ventricular assist device (LVAD) implantation are not well‐established.ObjectivesThis study aimed to predict the factors associated with late sustained VAs after LVAD implantation and develop a predictive score to identify patients with an increased risk of late sustained VAs after the procedure.MethodsWe performed a retrospective cohort study on a training cohort of 623 patients and a validation cohort of 157 patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2000, to December 30, 2020. Late sustained VAs were defined as ventricular tachycardia (VT) and ventricular fibrillation (VF) occurring >30 days after the LVAD procedure. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.ResultsA total of 780 patients were included in our study. Late sustained VAs occurred in 30% (n = 232) of the patients. The significant factors associated with late sustained VAs after LVAD were the history of VAs prior to LVAD (34.1% vs. 23.0%, p < 0.01), implantable cardiac defibrillator (ICD) (87.9% vs. 77.6%, p < 0.01) or cardiac resynchronization therapy (CRT) in situ (43.5% vs. 33.6%, p = 0.008), VT ablation prior to LVAD (5.2% vs. 1.8%, p = 0.010), use of amiodarone (49.1% vs. 38.7%, p = 0.007), use of mexiletine (15.5% vs. 5.7%, p < 0.01), and higher left ventricular end‐diastolic diameter (LVEDD) on echocardiography prior to LVAD implantation (71.4 vs. 68.7 mm, p = 0.002). During follow‐up, the patients who developed late sustained VAs after LVAD had lower survival than those who did not (HR = 1.96, 95% CI:156–2.4, p < 0.001). The average time from LVAD to orthotopic heart transplant was longer among late sustained VAs patients (23 vs. 14 months, p < 0.01). The “VIN” risk score was created to identify four risk groups: low (scores 0), intermediate (score 1), high (score 2), and very high (score 3). The rates of late VA's in the training cohort at 1 year were 9.5%, 14%, 18%, and 25% which was almost similar to the risk of late VA's at validation cohort 10%, 12%, 20%, and 63%, respectively.ConclusionsLate sustained VAs occurred in 30% of the patients who received LVAD and were associated with lower survival. The VIN risk score was developed and validated to stratify patients into low, intermediate, high, and very high risk of late sustained VAs.