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Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.

Abstract Background Celiac disease (CeD) is a T-cell mediated enteropathy driven by gluten in genetically susceptible individuals. Mucosal inflammation persists for years even when treated with a gluten-free diet (GFD). Although patients may be advised to increase dietary fibre, some fibres are poorly tolerated leading, potentially, to suboptimal fibre intake and hampering dietary recommendations. Aims Our project aims to investigate whether and how the supplementation of two fibre types with distinct functional profiles affects the recovery of gluten-immunopathology in a mouse model of gluten-sensitivity. We hypothesize that: (1) HylonVII, but not inulin, accelerates mucosal recovery by increasing microbial carbolytic activity and production of short-chain fatty acids (SCFA); (2) fibre intake is decreased in CeD patients, leading to decreased SCFA production. Methods NOD-DQ8 mice were immunized to gliadin and then placed on a gluten-containing diet. Three weeks later, mice were returned to GFD supplemented with or without HylonVII or inulin to 15% total fibre, for 6, 10, or 12 weeks. Recovery from gluten-induced pathology was evaluated by counting CD3+ intraepithelial lymphocytes (IELs) in villi tips and measuring villus-to-crypt (V/C) ratios in the small intestine. Adult CeD patients (newly diagnosed n=6 and GFD-treated n=7) and healthy controls (n=5) completed a food frequency questionnaire (Victoria DQES v2) and provided fecal samples for evaluation of SCFA production. Fecal SCFA were measured with targeted single ion monitoring gas-chromatography/mass-spectrometry (Agilent) as markers of fibre metabolism. Results In gluten immunized mice, 3 weeks of wheat diet led to increased CD3+ IEL counts and decreased V/C ratios (pampersand:003C0.01), which remained abnormal after 6 weeks of GFD. Mice consuming GFD+inulin, but not HylonVII, normalized CD3+ IELs and V/C ratios, had higher fecal SCFAs (pampersand:003C0.05) (primarily acetate), and a higher carbolytic-proteolytic metabolite ratio (pampersand:003C0.05) compared with mice consuming a GFD alone for six weeks. Only 1/7 patients with CeD on GFD met the minimum recommendation for fibre intake (25 g/day, Health Canada), compared with 5/11 participants on gluten-containing diets. SCFA production was impaired in active but not in treated CeD patients (2563 vs 3744 μg/g, pampersand:003C0.01). Conclusions In gluten-immunized NOD-DQ8 mice, GFD+inulin accelerates mucosal recovery, which is associated with increased fecal SCFA. In our pilot clinical data, patients on a GFD did not meet the recommendation for fibre intake although they were capable of metabolizing fibre to produce SCFA that could facilitate mucosal recovery. Together these results suggest that CeD on GFD may benefit from increasing fibre, such as inulin, during the GFD. Funding Agencies CIHRCeliac Canada

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5–30 mg every 2 weeks or 2–10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines. Our review indicates that 5 mg weekly or lower should be prescribed when initiating injectable estrogens to avoid supraphysiologic E2 levels.

Objective We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL‐PAN). Methods Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease‐related damage, and survival were analyzed. Results Three hundred fifty‐eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty‐five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow‐up, relapse occurred in 48.5% of patients. One, 5‐ and 10‐year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 μmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. Conclusion The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 μmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN. image

Objective To evaluate the incidence and outcomes of large artery (LA) involvement among patients with giant cell arteritis (GCA) and to compare LA involvement to non-GCA patients. Methods The study included Olmsted County, Minnesota, USA residents with incident GCA between 1950 and 2016 with follow-up through 31 December 2020, death or migration. A population-based age-matched/sex-matched comparator cohort without GCA was assembled. LA involvement included aortic aneurysm, dissection, stenosis in the aorta or its main branches diagnosed within 1 year prior to GCA or anytime afterwards. Cumulative incidence of LA involvement was estimated; Cox models were used. Results The GCA cohort included 289 patients (77% females, 81% temporal artery biopsy positive), 106 with LA involvement. Reported cumulative incidences of LA involvement in GCA at 15 years were 14.8%, 30.2% and 49.2% for 1950–1974, 1975–1999 and 2000–2016, respectively (HR 3.48, 95% CI 1.67 to 7.27 for 2000–2016 vs 1950–1974). GCA patients had higher risk for LA involvement compared with non-GCA (HR 3.22, 95% CI 1.83 to 5.68 adjusted for age, sex, comorbidities). Thoracic aortic aneurysms were increased in GCA versus non GCA (HR 13.46, 95% CI 1.78 to 101.98) but not abdominal (HR 1.08, 95% CI 0.33 to 3.55). All-cause mortality in GCA patients improved over time (HR 0.62, 95% CI 0.41 to 0.93 in 2000–2016 vs 1950–1974) but remained significantly elevated in those with LA involvement (HR 1.89, 95% CI 1.39 to 2.56). Conclusions LA involvement in GCA has increased over time. Patients with GCA have higher incidences of LA involvement compared with non-GCA including thoracic but not abdominal aneurysms. Mortality is increased in patients with GCA and LA involvement highlighting the need for continued surveillance.

Introduction: Acute ischemic stroke (AIS) patients often require multiple passes during mechanical thrombectomy (MT) to open the vessel. Yet, at times, even numerous passes are unsuccessful. This study aims to investigate the impact of the number of passes on the outcomes of patients who underwent failed MT. Methods: We used Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to August 2023. Patients who underwent MT for ICA, M1, or M2 with unsuccessful recanalization (modified Thrombolysis in Cerebral Infarction ≤ 2a) were included. Primary outcome was 90- day modified Rankin Scale (mRS) 0-2. Secondary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Outcomes were compared among patients who received ≤ 2, 3, 4, and ≥ 5 MT passes. Results: 736 patients met inclusion criteria. 90-day mRS 0-2 was found to decrease with number of passes (Figure 1). Multivariate logistic regression analysis revealed that 3 passes (OR: 0.48, 95% CI: 0.23 -0.96, P-value: 0.04), 4 passes (OR: 0.46, 95% CI: 0.19 -1.03, P-value: 0.07), and ≥ 5 passes (OR: 0.22, 95% CI: 0.08 -0.50, P-value: <0.001) were associated with lower odds of mRS 0-2 compared to ≤ 2 passes. However, there were no significant differences between groups in ICH, sICH, or 90-day mortality. Conclusion: The number of passes affects functional outcomes among stroke patients who underwent failed MT.

Introduction: The benefits of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with unsuccessful mechanical thrombectomy (MT) are not well established. Methods: This study included patients from the Stroke Thrombectomy and Aneurysm Registry (STAR) who underwent MT for ICA, M1, or M2 occlusions with unsuccessful MT (mTICI score ≤ 2a). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score (PS) matching was performed using age, sex, premorbid modified Rankin Scale (mRS), admission National Institute of Health Stroke Scale (NIHSS), occluded vessel, ASPECTS score, mTICI score, and symptom onset to groin puncture time. The primary outcome was favorable 90-day outcomes (mRS 0-2). Results: Of 610 patients with unsuccessful MT, 219 were matched in each group. Median ages were 70 [IQR: 61 - 80] and 73 [IQR: 62 - 81] in the IVT + MT and MT alone groups, respectively. In the IVT + MT group. Final TICI scores of 0, 1, and 2a were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, compared to 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group showed a significantly. higher 90-day mRS of 0-2 (aOR: 2.54, 95% CI: 1.53-4.32) and mRS of 0-3 (aOR: 2.05, 95% CI: 1.36-3.12). There were no significant differences between the groups in intracranial hemorrhage (ICH), symptomatic ICH, or 90-day mortality rates. Conclusions: IVT is associated with improved functional outcomes in patients with unsuccessful MT. Ensuring that IVT is provided to all eligible stroke patients should remain a priority.

Introduction: Up to 50% of acute ischemic stroke (AIS) patients who undergo successful mechanical thrombectomy (MT) fail to achieve favorable outcomes (futile recanalization). In this study we aim to develop a machine learning (ML) model to predict futile recanalization (FR) in AIS patients who undergo MT. Methods: We used data from an ongoing large, multicenter database from 2013 to 2023. We included AIS patients treated with MT for ICA, M1, or M2 occlusion with successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score ≥ 2C) and procedure durations under 60 minutes. FR was defined as successful recanalization with 90-day modified Rankin Scale (mRS) 3-6. The dataset was divided into 75% for training and 25% for external validation. Using the Caret Package in R, multiple models were tested, and their performances were evaluated by the area under the curve (AUC) of receiver operating. Both baseline and pre-interventional characteristics were incorporated into the model. The selected model was then externally validated on a 25% validation dataset. Results: Among 2,546 qualified patients, FR occurred in 1,342 (52.7%). In univariate analysis, baseline characteristics were significantly different between FR and non-FR groups. The M5P model demonstrated the highest performance (AUC: 0.833; 95% CI: 0.7989-0.852; PPV: 0.8101) in comparison to other tested models such as logistic regression (AUC: 0.74), RF (AUC: 0.78), J48 (AUC: 0.78), SVM (AUC: 0.79), and GB (AUC: 0.79). The external validation of the model showed satisfactory results (AUC: 75.25; 95% CI: 70-80; PPV: 76.87). Conclusion: Utilizing clinical, pre-procedural, and imaging parameters, the M5P model can efficiently predict F) in AIS patients before attempting MT. This tool can assist neurointerventionalists in adequately choosing their MT candidates.

Background: Mechanical thrombectomy (MT) has significantly reduced morbidity and mortality in acute ischemic stroke (AIS). This study aims to analyze the outcomes and factors associated with decompressive hemicraniectomy (DHC) in AIS patients who underwent MT. Methods: We retrospectively analyzed data from an ongoing, multicenter database to investigate AIS patients who underwent MT for ICA, M1, or M2 occlusion. We compared clinical and procedural variables between patients who underwent DHC and those who did not. Propensity score (PS) matching between the two groups was conducted using age, sex, admission NIHSS, occluded vessel, ASPECTS, time from symptoms onset to arterial puncture, intracranial hemorrhage (ICH), and symptomatic ICH (sICH). Results: Among the 3,135 MT patients who met our inclusion criteria, 113 underwent DHC. A 1:3 propensity matching yielded a well-matched cohort of 113 in the DHC group versus 339 in the non-DHC group. The DHC group had a significantly higher rate of successful recanalization (mTICI ≥ 2C) (175 [51.6%] versus 36 [31.9%], P < 0.001) and a longer procedure duration, with a median of 30 minutes (IQR: 17-54) compared to 44 minutes (IQR: 25-78) in the non-DHC group (P = <0.001). Further comparison of patients with low ASPECTS (≤ 5) who underwent DHC (n = 36) with those who did not (n = 99) showed no significant difference in successful recanalization rates (15 [41.7%] versus 43 [43.4%], P > 0.90). However, procedure duration was significantly longer in the DHC group with a median of 29 minutes (IQR: 13-52), compared to 39 minutes (IQR: 27-86) in the non-DHC group (P = 0.02). Conclusions: Successful recanalization can help in preventing DHC in AIS patients with high ASPECTS, but not those with low ASPECTS. Procedure duration is independently related to DHC following MT, especially in low ASPECTS patients.