Citations

Objective To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

ABSTRACTObjectivesTo achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face.Materials and MethodsDelphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9‐point Likert scale (1 = strongly disagree; 9 = strongly agree) and optionally provided comments. The consensus meeting was supplemented by the results of a systematic review of the literature (from 2000 to 2023).ResultsTwo rounds of Delphi survey were completed by 34 participants across four countries. Represented specialties were dermatology, facial plastic surgery, plastic surgery, and oculoplastic surgery. The initial 105 statements from round 1 expanded to 112 in round 2, with 96 statements achieving consensus. These included possible adverse events (11 statements); absolute and relative contraindications to treatment (5 statements); preoperative care and antimicrobial prophylaxis precautions (16 statements); intraoperative precautions (17 statements); postoperative care (21 statements); monitoring for and management of infection (16 statements); management of pigmentation changes (6 statements); and management of scarring and incipient scarring (4 statements).ConclusionAn international consensus statement was developed for the prevention and management of complications associated with fully ablative laser resurfacing of the face. While expert practices vary, key factors for optimizing outcomes include careful patient selection, counseling, and meticulous pre‐ and postoperative care. Further research will improve our understanding of this treatment technique.

BACKGROUND: Surgical intervention remains an important option in the management of vestibular schwannoma (VSs). Development of a systematic approach to choose the most appropriate route for this intervention, based on existing published evidence, is an important goal. OBJECTIVE: To review the literature published since the 2018 Congress of Neurological Surgeons Guideline on surgical intervention for patients with sporadic VSs and use this information to update that set of recommendations. METHODS: The literature in the PubMed and MEDLINE databases from January 2015 through May 20, 2022, was searched for manuscripts pertaining to surgical intervention for VSs. Those manuscripts meeting inclusion criteria were then analyzed for creation of recommendations in response to a set of updated questions. RESULTS: The resultant findings included a considerable amount of data that did not alter the recommendations form the 2018 publication on this topic. Thus, recommendations stating hearing preservation surgery through the middle fossa or retrosigmoid approach may be considered in individuals with good preoperative hearing as an alternative to simple observation remain. In addition, if microsurgical resection is necessary after stereotactic radiosurgery, it is recommended that patients be counseled that there is an increased likelihood of a subtotal resection and decreased facial nerve function. In some questions, insufficient data were present to create an answer and that is stated. CONCLUSION: This guideline demonstrates surgical intervention for VSs and represents a range of options, and the choice of the intervention depends on the specific aspects of the lesion and the individual that harbors them. Objective refinement of those choices will require thoughtful research design by investigations that wish to address those items for which we still have insufficient information. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/7-surgical-resection-treatment-of-patients-with-ve-2

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

BACKGROUND: Given the increasing prevalence and shifting disease demographic of vestibular schwannoma toward smaller tumors in people with less advanced symptoms, increasing emphasis has been placed on functional hearing preservation. OBJECTIVE: To provide an update to the 2018 CNS Guideline on hearing preservation outcomes in patients with sporadic vestibular schwannoma. METHODS: Systematic review and clinical practice guideline summarizing data pertaining to hearing preservation outcomes within the first 10 years after contemporary stereotactic radiation, microsurgery, or observation with serial imaging. The analysis incorporates studies included in the 2018 guideline and additional literature published up to May 20, 2022, providing a comprehensive up-to-date review of published clinical outcome data over time. RESULTS: Pooled estimated rates of serviceable hearing preservation are presented for observation, radiosurgery, and microsurgery for adults with sporadic vestibular schwannoma who have documented serviceable hearing in the ipsilateral ear at the time of diagnosis. Overall estimated rates of maintaining serviceable hearing are 78% at 2 years, 59% at 5 years, and 47% at 10 years during observation; 71% at 2 years, 59% at 5 years, and 38% at 10 years after radiosurgery; and 48% at 2 years, 40% at 5 years, and 32% at 10 years after microsurgery. In addition, features portending hearing outcome among management modalities are reported to guide accurate patient counseling. CONCLUSION: Regardless of treatment modality, fewer than half of patients with sporadic vestibular schwannoma who present with serviceable hearing will maintain useful hearing by 10 years. Across all studies, microsurgery and radiosurgery seem to accelerate this decline over the natural history, although further research is needed given limitations of available evidence. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/4-hearing-preservation-outcomes-in-patients-with-s

BACKGROUND: Intraoperative neuromonitoring (IONM) has become vital in the management of vestibular schwannoma (VS) with the paradigm shift from tumor eradication to functional preservation. Several facial nerve (FN) monitoring strategies have been explored over the past few decades ranging from free-running electromyography, direct nerve stimulation, continuous nerve stimulation, facial motor evoked potentials, blink reflex, and others. Hearing preservation surgery is guided primarily by far-field auditory brainstem response and real-time cochlear nerve action potentials. Given the heterogeneity in tumor and patient factors, it remains very difficult to accurately predict cranial nerve outcomes, regardless of the monitoring strategy. OBJECTIVE: To critically appraise literature regarding IONM during VS surgery and update the previous evidence-based clinical practice guideline. METHODS: This is a systematic review of the literature, incorporating articles from March 2015 to May 2022. Literature published before 2015 that would have been included in the previous Congress of Neurological Surgeons guideline was not searched again in this update. RESULTS: FN monitoring provides better functional outcomes compared with anatomic dissection alone and may guide the extent of tumor resection. While facial motor evoked potentials and free-running electromyography can provide continuous noninvasive FN monitoring, there are insufficient data to determine which more strongly correlates with facial function outcomes. Both electrophysiological data and tumor size correlate with facial function outcomes. The ideal hearing monitoring strategy remains unclear as there are insufficient data comparing cochlear nerve action potentials with far-field auditory brainstem response. All studies were graded as Class III evidence. CONCLUSION: IONM should be used in all VS cases. While the optimal FN and hearing monitoring strategy remains elusive, available data support the use of a combination of strategies, including preoperative tumor size, to maximize sensitivity and specificity. There remains a significant need for high-quality comparative studies to determine which intraoperative monitoring scheme can provide intraoperative guidance and predict postoperative outcome. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/3-intraoperative-cranial-nerve-monitoring-in-manag

BACKGROUND: Stereotactic radiosurgery (SRS) is an established modality for treatment of adult patients with vestibular schwannomas (VS). The aim of this work was to provide an updated literature review on this topic. OBJECTIVE: To review the literature published since the last guideline on this topic. METHODS: OVID MEDLINE and Embase were searched for the period January 1, 2015, to May 20, 2022, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived. RESULTS: From the total 1035 abstracts identified, 26 full-text articles met inclusion/exclusion criteria and were included in this update. Four new level III recommendations stemmed from this work. In adult patients with sporadic intracanalicular or <2 cm VS, SRS should not be recommended as superior to observation alone for hearing preservation. In adult patients with sporadic VS treated with SRS, cochlear dose constraint should be considered because it provides better hearing preservation than no constraint. In the same population, single fraction SRS should be recommended rather than hypofractionated SRS (>1 and ≤5 fractions) because it results in decreased cranial nerve dysfunction. Finally, adult patients with sporadic VS undergoing SRS should be informed that SRS does not result in an increased number of secondary malignancies compared with the rate expected in the overall population. CONCLUSION: Recent published literature provides new recommendations for the treatment of adult patients with VS with SRS. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/6-role-of-radiosurgery-srs-radiation-therapy-in-ma

Abstract Background Cardiovascular guidelines have long recommended low-density lipoprotein-cholesterol (LDL-C) as the primary target for lipid-lowering therapy. Recent guidelines have emphasized the importance of achieving low LDL-C levels; hence, the accurate measurement of low LDL-C is increasingly clinically relevant. Methods Using lipid panel test results from the Mayo Clinic (n = 24 590) and the FOURIER clinical trial of evolocumab (n = 9605), the following modified Sampson equation was developed by least-squares regression to match LDL-C (mg/dL) by the β-quantification reference method, by combining terms into non High Density Lipoprotein Cholesterol (nonHDLC = Total Cholesterol – High Density Lipoprotein Cholesterol) and forcing the coefficient to be one: Results The modified Sampson equation demonstrated significant improvement in its concordance to the reference method compared to other equations (the Lin Concordance Correlation Coefficient 0.992, P &lt; 0.001). By overall kappa analysis, it showed the best agreement to the reference method at the 55 mg/dL cutpoint (1.4 mmol/L, 0.98 [P &lt; 0.001], Sampson–NIH: 0.96, Martin–Hopkins: 0.96, Friedewald: 0.94) and the 70 mg/dL cutpoint (1.8 mmol/L, 0.97 [P &lt; 0.001], Sampson–NIH: 0.94, Martin–Hopkins: 0.95, Friedewald: 0.92). The false classification rate of the modified Sampson equation was also significantly lower compared to the other equations at 55 mg/dL (15%, [P &lt; 0.001], Sampson–NIH: 29%, Martin–Hopkins: 28%, Friedewald: 37%) and 70 mg/dL (18%, [P &lt; 0.001]; Sampson–NIH: 30%, Martin–Hopkins: 28.%, Friedewald: 34%). The new equation increases the percentage of correctly classified patients with low LDL-C by approximately 10% to 20% over the other equations based on its net reclassification index. Conclusions The modified Sampson equation shows improved accuracy compared to other equations for low LDL-C. It more accurately identifies high-risk patients, who are not at their LDL-C goals and could benefit from more intensive lipid-lowering therapy.

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.