Citations

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14–29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7–3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4–7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0–6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38–0.83]; P =0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31–0.77]; P =0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14–0.45]; P <0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Abstract Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. Patients and Methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0–2 at 3 months. Results: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10–2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93–0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59–3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25–0.72) and 0.55 (95% CI, 0.39–0.77), respectively. Conclusion: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Objective The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. Study Design Survey. Setting A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. Results House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. Conclusions Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.

Abstract The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

OBJECTIVE The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.

Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development.

Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65–89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC −0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.