Citations

Background Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract ( d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [ rsp] = −0.56, p < 0.001), and forceps minor of corpus callosum ( rsp = -0.45, p < 0.01). Conclusion MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

AbstractBackgroundAppropriate time for ejection fraction (EF) reassessment after revascularization in patients with left ventricular dysfunction has not been investigated comprehensively, although 3 months after revascularization is recommended to stratify the risk of sudden cardiac death (SCD).HypothesisEF reassessed within different timeframe after revascularization may have incosistent contribution for risk stratification of SCD.MethodsPatients who had EF ≤ 40% before revascularization and had EF reassessment at least once during follow‐up were included. The role of early (<3 months) versus late (3–12 months) EF measurements in prediction of all‐cause mortality and SCD were compared.ResultsA total of 1589 patients were identified. EF reassessed <3 months was lower than EF reassessed within 3–12 months (42.1 ± 9.7% vs. 45.8 ± 10.8%; p < .01). Among 1069 patients who had EF reassessed <3 months, EF ≤ 35% was associated with a higher risk of all‐cause mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.22–2.29; p < .01), but had no association with the risk of SCD (HR, 1.44; 95% CI, 0.84–2.48; p = .18). By contrast, among 595 patients who had EF reassessed within 3–12 months, EF ≤ 35% was associated with higher risks of both all‐cause death (HR, 1.81; 95% CI, 1.06–3.10; p = .03) and SCD (HR, 2.71; 95% CI, 1.31–5.61; p < .01). The relative contribution of SCD to all‐cause death was higher in patients with EF ≤ 35% than patients with EF > 35% when EF was reassessed within 3–12 months (p = .04). However, when EF was reassessed <3 months, the mode of death was similar in patients with EF ≤ 35% versus >35% (p = .85).Conclusions3 to 12 months after revascularization may be appropriate for cardiac function reassessment and SCD risk stratification.

Abstract Endpoint adjudication (EA) is a common feature of contemporary randomized controlled trials (RCTs) in cardiovascular medicine. Endpoint adjudication refers to a process wherein a group of expert reviewers, known as the clinical endpoint committee (CEC), verify potential endpoints identified by site investigators. Events that are determined by the CEC to meet pre-specified trial definitions are then utilized for analysis. The rationale behind the use of EA is that it may lessen the potential misclassification of clinical events, thereby reducing statistical noise and bias. However, it has been questioned whether this is universally true, especially given that EA significantly increases the time, effort, and resources required to conduct a trial. Herein, we compare the summary estimates obtained using adjudicated vs. non-adjudicated site designated endpoints in major cardiovascular RCTs in which both were reported. Based on these data, we lay out a framework to determine which trials may warrant EA and where it may be redundant. The value of EA is likely greater when cardiovascular trials have nuanced primary endpoints, endpoint definitions that align poorly with practice, sub-optimal data completeness, greater operator variability, and lack of blinding. EA may not be needed if the primary endpoint is all-cause death or all-cause hospitalization. In contrast, EA is likely merited for more nuanced endpoints such as myocardial infarction, bleeding, worsening heart failure as an outpatient, unstable angina, or transient ischaemic attack. A risk-based approach to adjudication can potentially allow compromise between costs and accuracy. This would involve adjudication of a small proportion of events, with further adjudication done if inconsistencies are detected.

Background Distal transradial artery access (dTRA) has received increasing consideration for performing diagnostic cerebral angiography and neurointerventional procedures. In this meta-analysis, we aim to evaluate the safety and efficacy of dTRA compared to conventional transradial access (cTRA) for cerebral angiography and neurointerventions. Method A systematic review and meta-analysis were conducted on studies investigating outcomes of dTRA and cTRA in neurointerventions. The primary outcome was technical success rates. Secondary outcomes included access site complication rates, crossover rates to alternative vessels, fluoroscopy time, and contrast volume. The random effects model was used to calculate the mean difference (MD) and odds ratios (OR) with 95% confidence intervals (Cl). Results Eight retrospective observational studies with a total of 1477 patients who underwent 1175 diagnostic cerebral angiography and 516 neurointerventional procedures using 546 dTRA and 1164 cTRA approaches were included in our meta-analysis. The technical success rate was similar between dTRA and cTRA groups (95.8% vs 91.4%; OR:1.65; 95% Cl: 0.52 to 5.22; P = 0.40). Similarly, no difference was seen in dTRA and cTRA regarding access site complications (2% vs 1.4%; OR: 1.31; 95% CI: 0.47 to 3.61; P = 0.61) and access site crossover (2.1% vs 5.3%; OR: 0.55; 95% Cl: 0.28 to 1.05; P = 0.07). After resolving heterogeneity among included studies, dTRA was associated with a shorter fluoroscopy time (MD: −0.91 min; 95% CI: −1.74 to −0.09; P = 0.03) and lower contrast volume (MD: −8.32 mL; 95% CI = −14.7 to −1.94; P = 0.011). Conclusion Our findings suggest that the dTRA approach is a safe and effective alternative to the cTRA approach in patients undergoing cerebral angiography and neurointerventions.

Abstract This is a case of a 26-year-old male patient, with relapsing Hodgkin lymphoma, treated with nivolumab and brentuximab-vedotin, who was admitted with hyperglycemia and severe insulin resistance requiring approximately 2000 units of intravenous insulin per day. He had no prior diagnosis of diabetes. He was eventually diagnosed with massive cytokine release and hemophagocytic lymphohistiocytosis that led to multi-organ failure and death. The mechanisms behind the hyperglycemia with severe insulin resistance remain unclear but are possibly related to hyperinflammation and immune dysregulation resulting from massive cytokine release. Nivolumab among other immunotherapeutic agents, brentuximab-vedotin, and lymphoid malignancies are rare but known risk factors for massive cytokine release and hemophagocytic lymphohistiocytosis.

Background: Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. Methods: We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. Results: A total of 471 patients with lung cancer were included, of which 402 had non–small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69–16.92; P<.001; and HR, 2.81; 95% CI, 1.50–5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17–18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3–5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. Conclusions: Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.

Novel targeted therapies (small molecule inhibitors, antibody–drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton’s tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.