Citations

Abstract BACKGROUND Open surgery has traditionally been preferred for the management of bifurcation middle cerebral artery (MCA) aneurysms. Flow diverting stents present a novel endovascular strategy for aneurysm treatment. OBJECTIVE To add to the limited literature describing the outcomes and complications in the use of flow diverters for the treatment of these complex aneurysms. METHODS This is a multicenter retrospective review of MCA bifurcation aneurysms undergoing flow diversion. We assessed post-treatment radiological outcomes and both thromboembolic and hemorrhagic complications. RESULTS We reviewed the outcomes of 54 aneurysms treated with flow diversion. Four (7.4%) of the aneurysms had a history of rupture (3 remote and 1 acute). Fourteen (25.9%) of the aneurysms already underwent either open surgery or coiling prior to flow diversion. A total of 36 out of the 45 aneurysms (80%) with available follow-up data had adequate aneurysm occlusion with a median follow-up time of 12 mo. There were no hemorrhagic complications but 16.7% (9/54) had thromboembolic complications. CONCLUSION Flow diverting stents may be a viable option for the endovascular treatment of complex bifurcation MCA aneurysms. However, compared to published series on the open surgical treatment of this subset of aneurysms, flow diversion has inferior outcomes and are associated with a higher rate of complications.

PURPOSE COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC). METHODS This phase Ib study ( NCT03170960 ) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety. RESULTS A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs. CONCLUSION The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.

Abstract The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2-year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than were SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate (ORR) and complete response rate were 83% and 54% in ZUMA-1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit vs non–CAR T-cell salvage regimens for patients with refractory LBCL.

Abstract Succi, PJ, Dinyer, TK, Byrd, MT, Voskuil, CC, and Bergstrom, HC. Application of V̇ o 2 to the critical power model to derive the critical V̇ o 2 . J Strength Cond Res 36(12): 3374–3380, 2022—The purposes of this study were to (a) determine whether the critical power (CP) model could be applied to V̇ o 2 to estimate the critical V̇ o 2 (CV̇ o 2 ) and (b) to compare the CV̇ o 2 with the V̇ o 2 at CP (V̇ o 2 CP), the ventilatory threshold (VT), respiratory compensation point (RCP), and the CV̇ o 2 without the V̇ o 2 slow component (CV̇ o 2 slow). Nine subjects performed a graded exercise test to exhaustion to determine V̇ o 2 peak, VT, and RCP. The subjects performed 4 randomized, constant power output work bouts to exhaustion. The time to exhaustion (T Lim ), the total work (W Lim ), and the total volume of oxygen consumed with (TV̇ o 2 ) and without the slow component (TV̇ o 2 slow) were recorded during each trial. The linear regressions of the TV̇ o 2 vs. T Lim , TV̇ o 2 slow vs. T Lim , and W Lim vs. T Lim relationship were performed to derive the CV̇ o 2 , CV̇ o 2 slow, and CP, respectively. A 1-way repeated-measures analysis of variance ( p ≤ 0.05) with follow-up Sidak-Bonferroni corrected pairwise comparisons indicated that CV̇ o 2 (42.49 ± 3.22 ml·kg −1 ·min −1 ) was greater than VT (30.80 ± 4.66 ml·kg −1 ·min −1 ; p < 0.001), RCP (36.74 ± 4.49 ml·kg −1 ·min −1 ; p = 0.001), V̇ o 2 CP (36.76 ± 4.31 ml·kg −1 ·min −1 ; p < 0.001), and CV̇ o 2 slow (38.26 ± 2.43 ml·kg −1 ·min −1 ; p < 0.001). However, CV̇ o 2 slow was not different than V̇ o 2 CP ( p = 0.140) or RCP ( p = 0.235). Thus, the CP model can be applied to V̇ o 2 to derive the CV̇ o 2 and theoretically is the highest metabolic steady state that can be maintained for an extended period without fatigue. Furthermore, the ability of the CV̇ o 2 to quantify the metabolic cost of exercise and the inefficiency associated with the V̇ o 2 slow component may provide a valuable tool for researchers and coaches to examine endurance exercise.

Background: Spine injuries are common in collegiate wrestlers and can lead to reinjury, persistent pain, and time lost from participation. Purpose: To describe the epidemiology of spine injuries in National Collegiate Athletic Association (NCAA) wrestlers between academic years 2009 to 2010 and 2013 to 2014. Study Design: Descriptive epidemiology study. Methods: The incidence and characteristics of spine injuries were identified utilizing the NCAA–Injury Surveillance Program database. Spine injuries were assessed for injury type, injury mechanism, time of season, event type, recurrence, participation restriction, and time lost from participation. Rates of injury were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Injury rate ratios (IRRs) were calculated for event type and time of season, and results with 95% confidence intervals that did not include 1.0 were considered statistically significant. Results: There were an estimated 2040 spine injuries reported in the database over the 4-year period, resulting in an injury rate of 0.71 per 1000 AEs. Spine injuries were over twice as likely to occur in competitions as in practices (IRR, 2.02; 95% confidence interval, 1.10-3.69). More injuries occurred in both the preseason (0.94 per 1000 AEs) and the postseason (1.12 per 1000 AEs) compared with the regular season (0.55 per 1000 AEs). Contact injuries (42%) were the most common mechanism of injury, and brachial plexus injury (20%) was the most common diagnosis. Only 1.3% of injuries required surgery, and athletes most commonly returned to sport within 24 hours (33%) or within 6 days (25%). Conclusion: This investigation found an overall injury rate of 0.71 per 1000 AEs in wrestling athletes between academic years 2009 to 2010 and 2013 to 2014. The majority of these injuries were new, and athletes most commonly returned to sport within 24 hours. The injury rate was highest in competition, and both the preseason and the postseason showed a higher injury rate than that in season. Efforts to improve injury prevention and management should be informed by these findings.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow‐up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1‐year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1‐year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1‐point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5‐0.79) in the validation set. Independent predictors of death or transplant during follow‐up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1‐point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant‐free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.

4-Aminopyridine is a potential therapeutic option for a subgroup of patients with KCNA2 -encephalopathy and gain-of-function variants.

BACKGROUND Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS This was a retrospective, case–control, single institution, multi-center study. Univariate analysis was used. RESULTS Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Abstract Background and Aims To report results from VISIBLE 2, a randomised, double-blind, placebo-controlled, phase 3 trial evaluating a new subcutaneous [SC] vedolizumab formulation as maintenance treatment in adults with moderately to severely active Crohn’s disease [CD]. Methods Following open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2, Week 6 clinical responders (≥70-point decrease in CD Activity Index [CDAI] score from baseline) were randomised 2:1 to receive double-blind maintenance vedolizumab 108 mg SC or placebo every 2 weeks until Week 50. Assessments at Week 52 included clinical remission [primary endpoint; CDAI ≤150], enhanced clinical response [≥100-point decrease in CDAI from baseline], corticosteroid-free clinical remission among patients using a corticosteroid at baseline, clinical remission in anti-tumour necrosis factor [anti-TNF]-naïve patients, and safety. Results Following vedolizumab intravenous induction, 275 patients were randomised to vedolizumab SC and 135 to placebo maintenance. At Week 52, 48.0% of patients receiving vedolizumab SC versus 34.3% receiving placebo were in clinical remission [p = 0.008]. Enhanced clinical response at Week 52 was achieved by 52.0% versus 44.8% of patients receiving vedolizumab SC versus placebo, respectively [p = 0.167]. At Week 52, 45.3% and 18.2% of patients receiving vedolizumab SC and placebo, respectively, were in corticosteroid-free clinical remission, and 48.6% of anti-TNF-naïve patients receiving vedolizumab SC and 42.9% receiving placebo were in clinical remission. Injection site reaction was the only new safety finding observed for vedolizumab SC [2.9%]. Conclusions Vedolizumab SC is an effective and safe maintenance therapy in patients with CD who responded to two infusions of vedolizumab intravenous induction therapy.