Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes.

OBJECTIVE: Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored. RESEARCH DESIGN AND METHODS: We included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and 3-T MRI at baseline and 1-year post-BS. We assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEVs enriched for glial and astrocyte markers were determined by flow cytometry. RESULTS: Compared with control group, the obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the arcuate nucleus. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS. A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL 1 and 2 years after BS. CSF-lEVs did not differ among groups and were unrelated to WL trajectories. CONCLUSIONS: These findings suggest HI improvement after BS and may support a role for HI in modulating the WL response to these interventions.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.

Effectiveness of a network of automatically activated trained volunteers on the reduction of cardiopulmonary resuscitation manoueuvers initiation time: study protocol.

BACKGROUND: Cardiorespiratory arrest (CRA) is a health emergency with high mortality. Mortality depends on time of initiation and quality of cardiopulmonary resuscitation (CPR) manoeuvres and the use of the automated external defibrillator (AED). METHODS: The aim of the study is to determine the effectiveness of an automatically activated network of volunteers using smartwatch and smartphone applications on the reduction of time of initiation of cardiopulmonary resuscitation manoeuvres. The protocol will be developed in four phases: 1) validation of an application (App) for smartwatch that automatically generates a health alert in case of out-of-hospital cardiorespiratory arrest (OHCA); 2) training course for laypersons on CPR manoeuvres and AED use; 3) creation of a network of volunteers trained in CPR and AED use that covers our city; and 4) simulation in which the network of volunteers is automatically activated via smartphone to attend simulated OHCAs. A total of 134 health alerts will be generated; on 67 occasions the alert will be directed to the emergency health services and to the network of trained volunteers (Intervention Group) and on 67 occasions the alert will be solely directed to the emergency health services (Control Group). The arrival time of the first rescuer, category of first rescuer (emergency services versus network of volunteers), initiation time of manoeuvres and competence will be recorded. DISCUSSION: CPR training for laypersons is advised, especially for relatives and people close to patients with heart disease, to reduce time of initiation of CPR and to improve OHCA survival rates. This study aims to verify that the initiation time of CPR manoeuvres and AED use is shorter in the intervention than in the control group. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT03828305 . Trial registered on February 1, 2019 (retrospective register).