Citations

BACKGROUND: Imaging is a critical aspect of vestibular schwannoma (VS) management, influencing essentially every aspect of care including diagnosis, surveillance, treatment decision making, and follow-up after either resection or stereotactic radiosurgery. Despite this, treatment protocols are heterogeneous, and frequently based on historical practices, or low-quality evidence. OBJECTIVE: To update evidence-based guidelines for the use of imaging in the clinical management of patients with VS published by the Congress of Neurological Surgeons in 2018. METHODS: Systematic review of the literature published from 1/1/2015 to 5/20/2022 regarding imaging protocols for VS management. Salient questions were identified by a writing group of diverse individuals with topic-specific expertise. Questions were validated by the Congress of Neurological Surgeons Guidelines Committee. Following systematic review, literature tables and summary statements pertinent to the study questions were generated by the writing group, which underwent subsequent evaluation and revision by the task force before formalization. RESULTS: Seven questions were formulated; adequate literature was identified to formulate updated recommendations for 6 of these. Search strategy identified 1143 unique records, of which 109 underwent full-text review, and 57 were included in this study. Most studies provided level III evidence, with rare level II studies noted, yielding level III recommendations. CONCLUSION: The current evidence base for imaging protocols in VS clinical management is broad, diverse, low certainty, and low quality. This in part reflects a heterogeneous disease, although variability in treatment philosophies may also influence local decision making. Key areas for future study include the clinical utility of advanced imaging techniques and head-to-head comparisons of imaging protocols for patients in common initial VS management pathways (eg, observation, resection, or stereotactic radiosurgery). The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/5-role-of-imaging-in-management-of-patients-with-v

Osteoarthritis (OA) is a major global health problem with no disease-modifying therapies. Interleukin-1 (IL-1) is a critical cytokine associated with the pathophysiology of OA and can be inhibited by IL-1 receptor antagonist (IL-1Ra). Here, we tested the delivery of a gene therapeutic encoding the human IL-1Ra to the knee in a phase 1, open-label clinical trial that enrolled nine patients with radiographic knee OA. The IL-1Ra gene was delivered by a self-complementary (sc)–recombinant adeno-associated virus (rAAV) serotype 2.5 (sc-rAAV2.5IL-1Ra) by intra-articular injection into an index knee at one of three doses: low [1 × 10 11 viral genomes (vg)], mid (1 × 10 12 vg), or high (1 × 10 13 vg). The primary outcome was safety. There were no serious adverse events (AEs) related to sc-rAAV2.5IL-1Ra. Two AEs occurred that were possibly related to the vector. Both were effusions with increased pain and resolved with conservative treatment. sc-rAAV2.5IL-1Ra did not cause changes in vital signs, physical findings, or clinical laboratory measures. Less than 1% of the injected dose of sc-rAAV2.5IL-1Ra vg was detected in circulation after 1 day and was cleared within a week. Titers of neutralizing antibodies to AAV2.5 rose in serum and synovial fluid. In all cases, IL-1Ra concentration increased in the synovial fluid, and IL-1Ra concentrations remained elevated after 1 year. Baseline pain and function scores improved during the study. Therefore, we found that intra-articular gene therapy with sc-rAAV2.5IL-1Ra was safe. The sustained increase in local IL-1Ra in human knee joints supports the further clinical examination of this therapy to provide therapeutic benefit in OA.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

LBA1 Background: Standard adjuvant chemotherapy of stage III colon cancer consists of a fluoropyrimidine plus oxaliplatin. In patients (pts) with stage III colon cancer and deficient mismatch repair (dMMR), the benefit of an immune checkpoint inhibitor combined with adjuvant chemotherapy is unknown. The phase III ATOMIC trial (NCT02912559) was conducted to determine whether atezolizumab (atezo), an anti-PD-L1 antibody, can improve pt outcomes when added to adjuvant 5-fluorouracil, leucovorin plus oxaliplatin (mFOLFOX6) in pts with stage III dMMR tumors. Methods: We conducted an NCI-sponsored, multicenter and randomized phase III trial in pts with surgically resected stage III dMMR colon adenocarcinoma (any T, N 1,2 M 0 ). Pts, age > 12 years (yr), were accrued at NCTN sites and the German AIO. Tumor dMMR was determined by local immunohistochemistry and centrally verified. Pts were randomized 1:1 to mFOLFOX6 plus atezo (840 mg IV q2 weeks) for 12 cycles (6 months)[mo] followed by atezo monotherapy for 13 cycles (12 mo total) versus mFOLFOX6 alone for 12 cycles. Randomization stratification factors were N-stage (N 1 /N 1c vs N 2 ), T-stage (T 1 -T 3 vs T 4 ) and site (proximal vs distal). The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival and adverse event (AE) profile (CTCAE, PRO-CTCAE). Primary efficacy analysis was done in the intent-to-treat population; DFS was compared by arm (stratified log-rank test). Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a stratified Cox model; 3-yr DFS was determined by Kaplan-Meier method. Among 700 pts., 165 DFS events with two interim analyses (50% , 75% of events) yielded 90% power to detect HR 0.6 (3-yr DFS 75% vs. 84.2%) assuming exponential survival and 1-sided alpha (0.025). Results: From 9/2017 to 1/2023, 712 pts were randomized (1 pediatric) to either atezo plus mFOLFOX6 (n= 355; atezo arm) or mFOLFOX6 (n= 357). Median pt age was 64 yr. 55.1% were female. Among tumors, 83.8% were proximal, 46.1% were clinical low risk (T 1-3 N 1 ) and 53.9% high risk (T 4 and/or N 2 ). At the second interim analysis, median pt follow-up was 37.2 mo (interquartile range, 24.2 to 55.5) and 124 DFS events were observed. Three-year DFS was 86.4 % (95% CI, 81.8 to 89.9) in the atezo arm and 76.6 % (95% CI, 71.3 to 81.0) in the mFOLFOX6 arm (HR, 0.50; 95% CI, 0.35 to 0.72). Stratified log-rank p-value was <0.0001, crossing the pre-specified efficacy boundary of 0.009. Efficacy for the atezo arm was consistent across subgroups, including pts >70 yr and low- and high-risk groups. Treatment-related > grade 3 AEs occurred in 71.7 % of pts in the atezo arm vs 62.1 % in the mFOLFOX6 arm. Conclusion: The addition of atezolizumab to mFOLFOX6 significantly improved DFS and should be considered the new adjuvant standard of care for patients with dMMR stage III colon cancer. Support: U10CA180821, U10CA180882, U24CA196171; Genentech, a member of the Roche group; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02912559 .

Background: There has been minimal literature evaluating how a prior myocardial infraction (MI) influences outcomes after total knee arthroplasty (TKA). Thus, the purpose of this study was to evaluate how the timing, type, and treatment of MI prior to TKA affect postoperative cardiac complications, general medical complications, and surgical complications. Methods: A retrospective comparative study was conducted using a large insurance database. Patients undergoing primary TKA for osteoarthritis were included. Patients who had experienced MI within 2 years before TKA were identified and were matched 1:4 with patients who had not had such an MI on the basis of demographic variables and comorbidities. Patients who had a prior MI were stratified into 4 groups based on the timing of the MI: 0 to <6 months, 6 to <12 months, 12 to <18 months, and 18 to 24 months before TKA. The rates of postoperative cardiac, general medical, and surgical complications were compared between groups. Subanalyses on the prior MI type, treatment, and location were performed. Results: Prior MI was associated with increased risks of postoperative MI (odds ratio [OR], 3.97 [95% confidence interval (CI), 3.20 to 4.93]), heart failure (OR, 1.45 [95% CI, 1.24 to 1.75]), and 90-day mortality (OR, 2.15 [95% CI, 1.41 to 3.28]). The risk of postoperative MI was highest for those with MI within 6 months before TKA (OR, 6.86 [95% CI, 5.34 to 8.82]). Type-1 MI, ST-elevation MI (STEMI), non-ST-elevation MI (NSTEMI), and anterior and inferior MIs were linked to elevated postoperative MI and/or mortality risks, with timing closer to surgery further amplifying the risk. Percutaneous coronary intervention within 6 months before TKA also increased postoperative risks. Type-2 MI within 6 months before TKA was associated with an increased risk of periprosthetic joint infection compared with controls (OR, 4.23 [95% CI, 1.67 to 10.67]). Conclusions: Patients who had a prior MI, particularly within 6 months before TKA, had significantly elevated risks of postoperative MI, heart failure, and mortality. Outcomes varied by MI type, treatment, and location, with type-1 MIs and STEMIs increasing the postoperative mortality risk. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE The purpose of this study was to evaluate the risks and benefits of removing painful pelvic/iliac screws in spine fusion surgery patients. METHODS A retrospective review identified patients who had traditional iliac and S2-alar-iliac (S2AI) screws removed for pain. The minimum follow-up was 24 months. RESULTS Fifty-two patients (75% women) were included with a mean age of 63 years, BMI of 28, and follow-up of 65 months. Most of the removed screws were S2AI (83%) compared with traditional iliac screws (17%). Forty-three patients (83%) had improvement in their pelvic screw related–pain following removal. Eight patients (15%) experienced lumbosacral mechanical complications following pelvic screw removal including sacral fracture (n = 3, 6%) and/or L4–5 or L5–S1 rod fracture (n = 7, 13%). On multivariable analysis, risk factors for mechanical complications following pelvic screw removal included a longer fusion construct (OR 1.34, p = 0.035), greater postoperative L4–S1 lordosis (OR 1.14, p = 0.04, ideal cutoff > 40°), and lack of bone morphogenetic protein (BMP; OR 0.03, p = 0.02). Ten patients (19%) underwent subsequent SI joint fusion following pelvic screw removal, and higher standing pelvic incidence (OR 1.10, p = 0.03) was the only independent predictor of SI fusion. CONCLUSIONS Removal of painful pelvic screws resulted in a high rate of postoperative pain relief, albeit with a risk of lumbosacral mechanical complications and subsequent SI joint fusion. Patients at risk for lumbosacral mechanical complications following pelvic screw removal included those with longer fusion constructs, more lordosis from L4 to S1 (> 40°), and lack of BMP. Patients at risk for receiving an instrumented SI joint fusion following pelvic screw removal included those with a higher pelvic incidence.

Background: Evaluation of the performance of Cobas ® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip ® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. Results: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO 2 , hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. Conclusions: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

OBJECTIVE Chronic spinal degenerative diseases have been associated with reduced quality of life and dependency on others for personal needs and care. The change between preoperative and postoperative care dependency has yet to be explored in patients with cervical spondylotic myelopathy (CSM). In this retrospective study of a prospectively collected database, the authors evaluated the return to independence in performing self-care following surgical intervention for CSM. METHODS The CSM dataset of the Quality Outcomes Database (QOD) Spine CORe study group was queried. Care dependency was assessed using the personal care component of the Neck Disability Index (NDI) questionnaire, having an ordinal scale from 0 to 5, with 5 representing the inability to independently perform activities of daily living. Numeric rating scale (NRS) scores for arm pain and neck pain were recorded at a 24-months postoperative follow-up. Multivariable logistic regression analyses were performed to identify baseline risk factors for an inability to care for oneself and the symptoms leading to care dependency at 24 months postoperatively. Satisfaction with surgery was measured using the 4-point North American Spine Society (NASS) index. RESULTS Of the 1137 patients with CSM and baseline personal care scores, 167 (14.7%) were care dependent at baseline (NDI personal care score ≥ 3). Patients with care dependency at baseline were predominantly Medicare beneficiaries and had a high school or lower level of education. Long-term follow-up rates for this study were 82.5% for NDI, 84.8% for patient satisfaction with surgery, 82.4% for NRS arm pain, and 81.8% for NRS neck pain. Of the care-dependent patients, more than 80% became independently able to care for themselves by the 24-month follow-up. Patients with resolved care dependency at 24 months had demonstrated lower baseline NDI and NRS neck pain scores (p < 0.01 for both). Neck pain was significantly associated with care dependency at 24 months’ follow-up (p < 0.01). Patients who reported improvement in their ability to care for themselves noted higher postoperative satisfaction (NASS score 1–2) at the 3-month (89.4% vs 80.2%, p < 0.01) and 24-month (88.2% vs 67.4%, p < 0.01) follow-ups. CONCLUSIONS Fifteen percent of patients with CSM depended on others for care preoperatively. After surgery to treat CSM, 81.8% of those who had depended on others for care became independent. Patients with improvements in care dependency noted higher postoperative satisfaction at the 3-month and 24-month follow-ups. Patients with resolved care dependency on long-term follow-up had lower NDI and NRS neck pain scores at baseline. Surgery had a significant impact on patients’ attainment of independence.