Early and Delayed Infarct Growth in Patients Undergoing Mechanical Thrombectomy: A Prospective, Serial MRI Study.

BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

ZDHHC9 X-linked intellectual disability: Clinical and molecular characterization.

The ZDHHC9 gene encodes the Zinc Finger DHHC-Type Containing 9 protein that functions as a palmitoyltransferase. Variants in this gene have been reported as the cause of Raymond-type X-linked intellectual disability with only 16 families described in the literature. This study reviews molecular and clinical data from previously reported patients and reports the case of a 13-year-old patient with a splicing variant in ZDHHC9 presenting intellectual disability, developmental delay, facial dysmorphisms, and skeletal defects. Although intellectual disability and developmental delay with severe speech delay have been reported in all cases with available clinical data, the remaining clinical signs differ significantly between patients. Missense, nonsense, frameshift, and splicing variants, in addition to large exonic deletions, have been described suggesting a loss of function mechanism. Though variants are distributed in almost all exons, most missense and nonsense variants affect arginine residues located in the cytoplasmic domains of this transmembrane protein, suggesting possible mutational hotspots.

Aortic valve Replacement compared to Transcatheter Implant and its relationship with COgnitive Impairment (ARTICO) evaluated with neuropsychological and advanced neuroimaging: a longitudinal cohort study.

BACKGROUND: Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI). Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups. METHODS/DESIGN: Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline. DISCUSSION: This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making. TRIAL REGISTRATION: This study is register in Clinicaltrials.gov (NCT05235529) on 11th February 2022.

Non-Functional Carotid Body Tumors in Patients Without Somatic Mutations May Be Considered for Non-Operative Management.

BACKGROUND: Carotid Body Tumors (CBT) are rare neuroendocrine paragangliomas which are typically asymptomatic and benign, with a low rate of biochemical functionality. Historically, early surgical excision was recommended to prevent development of CBT-related complications. Yet, CBT resection can result in significant cranial nerve and vascular injuries. Recent work has shown successful primary observation without resection of non-carotid body, cranial paragangliomas with slow growth and low rate of neuropathies. We hypothesize that primary observation of CBT is safe and may be considered for majority of CBT. METHODS: Retrospective cohort study of patients at a multi-hospital healthcare system with radiologic identification and/or diagnostic or procedural billing codes for CBT (2000-2019). Tumor size (greatest diameter), associated symptoms, and interventions were recorded at the initial evaluation and throughout follow-up. Multivariable logistic regression investigated the risk of initial surgical resection. RESULTS: A total of 108 patients (mean age, 59 ± 19 years; 67% female), with 123 CBT (mean diameter 23 ± 12 mm; 52% right) were initially evaluated by otolaryngologists (51%), vascular surgeons (25%), neurosurgeons (8%), or other (16%) medical providers. Fity-five CBT were initially resected, 63 observed, and 5 irradiated. Initial resection was associated with younger age (adjusted odd ratios aOR, 0.95 [95% confidence intervals CI, 0.92-0.97]), male sex (aOR, 4.82 [95% CI, 1.47-15.75]), and evaluation by a vascular surgeon (aOR, 6.17 [95% CI, 2.04-18.63]). Overall median follow-up was 4.7 (IQR, 2.6-9.1) years. Initially observed CBT were on an average stable in size (mean 1 ± 5 mm/year), none became biochemically active, and 2 patients became symptomatic. At the final follow-up, 63 (51%) underwent surgical resection, 54 (44%) observation, and 6 (5%) radiation therapy. Of the 63 surgically resected CBT, 5 (8%) patients had malignant CBT of which 3 (60%) had known somatic mutations (polymerase epsilon [n = 1], succinate dehydrogenase-D gene [n = 2]). Thirty percent of CBT resections had in-hospital postoperative complications, notably including 1 stroke which occurred in an initially observed patient and 16 cranial nerve complications which all occurred in immediately resected patients. Three resected CBT locally recurred, only 1 of which had malignant pathology. CONCLUSIONS: Patients with newly diagnosed CBT require biochemical functionality and somatic mutation testing. In the absence of these findings, initial observation of CBTs with annual imaging and symptom monitoring may be considered an alternative to immediate resection which demonstrates a high risk of clinically meaningful postoperative complications.

Effect of irrigation protocol during post space preparation on the dentin adhesive interface: An in vitro study.

STATEMENT OF PROBLEM: The post space must be prepared with techniques that do not interfere with the bond strength. These techniques are related to the availability of opened dentinal tubules and incidence of residue among the dentin, the adhesive, and the cement. Nevertheless, the effect of different irrigants during endodontic instrumentation is unclear. PURPOSE: The purpose of this in vitro study was to assess the incidence of residue, the number of opened dentinal tubules, and the bond strength of the cementation system to root dentin of post space after 3 different irrigation protocols. MATERIAL AND METHODS: The roots of bovine incisors were obturated, prepared to receive a fiber post, and divided into 3 groups as per the irrigation protocol: without irrigation, with alternating irrigation, and with continuous irrigation. Thirty roots (n=10) were evaluated by using scanning electron microscopy to assess the incidence of residue (×100 magnification) and the number of opened dentinal tubules (×2000 magnification). The fiber posts were cemented, and the remaining specimens (n=10) were subjected to pushout testing and failure mode evaluation. RESULTS: All protocols presented a similar incidence of residue, regardless of the post space third (P>.05). The irrigation protocol without irrigation had the lowest number of opened dentinal tubules in the cervical and middle thirds (P<.05). The number of opened dentinal tubules was similar in all protocols in the apical third of the post space (P>.05). The irrigation protocol without irrigation had the lowest bond strength values in the cervical and middle thirds (P<.05). The irrigation protocol with continuous irrigation had the highest bond strength values in the apical third (P<.05). CONCLUSIONS: Post space preparation without irrigation negatively affected the bond strength of the resin cementation system to root dentin.

Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise.

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.

Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity.

As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11 C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11 C]Ro15-4513 total distribution volume (VT ) in the right hippocampus in the GD group compared with HV. We found higher levels of the 'Negative Urgency' construct of impulsivity in GD, and these were positively associated with higher [11 C]Ro15-4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11 C]Ro15-4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.

Influence of microelement concentration on the intensity of alcohol withdrawal syndrome.

AIMS: To establish a nutritional and constitutional profile concerning the micronutrient plasma concentration of patients who suffer from AWS. METHOD: Observational case control study to determine whether patients who exhibited symptoms of AWS (N = 60) had micronutrient plasmatic concentration deficiencies when compared with healthy controls (N = 34). RESULTS: There were statistically significant differences between the concentrations of nutrients that are correlated with glutamate hyperactivity (zinc, magnesium and folate/vitamin B12/homocysteine). CONCLUSION: Evidence from literature and our experiment suggests that brain activity, especially the glutamatergic system, might be directly involved in micronutrient concentrations. Therefore, their supplementation to the AWS patient might improve symptom evolution.

Ouch, my pouch! a clinician's guide to pouchitis.

Pouchitis is defined as inflammation of the ileal pouch created during a restorative proctocolectomy with ileal pouch-anal anastomosis. Although the incidence of this inflammatory condition is high, the exact etiology often remains unclear and the management challenging. In this review, we summarize the clinical presentation, pathogenesis, diagnosis, and management of this common complication.

The role of cGAS in epithelial dysregulation in inflammatory bowel disease and gastrointestinal malignancies.

The gastrointestinal tract is lined by an epithelial monolayer responsible for selective permeability and absorption, as well as protection against harmful luminal contents. Recognition of foreign or aberrant DNA within these epithelial cells is, in part, regulated by pattern recognition receptors such as cyclic GMP-AMP synthase (cGAS). cGAS binds double-stranded DNA from exogenous and endogenous sources, resulting in the activation of stimulator of interferon genes (STING) and a type 1 interferon response. cGAS is also implicated in non-canonical pathways involving the suppression of DNA repair and the upregulation of autophagy via interactions with PARP1 and Beclin-1, respectively. The importance of cGAS activation in the development and progression of inflammatory bowel disease and gastrointestinal cancers has been and continues to be explored. This review delves into the intricacies of the complex role of cGAS in intestinal epithelial inflammation and gastrointestinal malignancies, as well as recent therapeutic advances targeting cGAS pathways.