APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation.

Importance: Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. Objective: To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM. Design, Setting, and Participants: This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status. Main Outcomes and Measures: For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression. Results: The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03). Conclusions and Relevance: The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.

Time-Dependent Changes in Hematoma Expansion Rate after Supratentorial Intracerebral Hemorrhage and Its Relationship with Neurological Deterioration and Functional Outcome.

BACKGROUND: Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. METHODS: We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up. RESULTS: The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) (p < 0.001). However, HE was an independent predictor of ND (p < 0.001), poor outcome (p = 0.010), and mortality (p = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH (p = 0.043, p = 0.037, and p = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND (p = 0.026), poor outcome (p = 0.037), and mortality (p = 0.027). CONCLUSION: Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.

Suboptimal Sleep Duration Is Associated With Poorer Neuroimaging Brain Health Profiles in Middle-Aged Individuals Without Stroke or Dementia.

BACKGROUND: The American Heart Association's Life's Simple 7, a public health construct capturing key determinants of cardiovascular health, became the Life's Essential 8 after the addition of sleep duration. The authors tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults. METHODS AND RESULTS: The authors conducted a prospective magnetic resonance neuroimaging study in middle-aged individuals without stroke or dementia enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers included the presence of white matter hyperintensities (WMHs), volume of WMH, and fractional anisotropy, with the latter evaluated as the average of 48 white matter tracts. Multivariable logistic and linear regression models were used to test for an association between sleep duration and these neuroimaging markers. The authors evaluated 39 771 middle-aged individuals. Of these, 28 912 (72.7%) had optimal, 8468 (21.3%) had short, and 2391 (6%) had long sleep duration. Compared with optimal sleep, short sleep was associated with higher risk of WMH presence (odds ratio, 1.11 [95% CI, 1.05-1.18]; P<0.001), larger WMH volume (beta=0.06 [95% CI, 0.04-0.08]; P<0.001), and worse fractional anisotropy profiles (beta=-0.04 [95% CI, -0.06 to -0.02]; P=0.001). Compared with optimal sleep, long sleep duration was associated with larger WMH volume (beta=0.04 [95% CI, 0.01-0.08]; P=0.02) and worse fractional anisotropy profiles (beta=-0.06 [95% CI, -0.1 to -0.02]; P=0.002), but not with WMH presence (P=0.6). CONCLUSIONS: Among middle-aged adults without stroke or dementia, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because these neuroimaging markers precede stroke and dementia by several years, these findings are consistent with other findings evaluating early interventions to improve this modifiable risk factor.

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Microbial and immune faecal determinants in infants hospitalized with COVID-19 reflect bifidobacterial dysbiosis and immature intestinal immunity.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed. CONCLUSION:  Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization. WHAT IS KNOWN: • Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults. • Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited. WHAT IS NEW: • The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system. • In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.

Polygenic Susceptibility to Hypertension and Cognitive Performance in Middle-aged Persons Without Stroke or Dementia.

BACKGROUND AND OBJECTIVES: Mounting evidence indicates that hypertension leads to a higher risk of dementia. Hypertension is a highly heritable trait, and a higher polygenic susceptibility to hypertension (PSH) is known to associate with a higher risk of dementia. We tested the hypothesis that a higher PSH leads to worse cognitive performance in middle-aged persons without dementia. Confirming this hypothesis would support follow-up research focused on using hypertension-related genomic information to risk-stratify middle-aged adults before hypertension develops. METHODS: We conducted a nested cross-sectional genetic study within the UK Biobank (UKB). Study participants with a history of dementia or stroke were excluded. We categorized participants as having low (≤20th percentile), intermediate, or high (≥80th percentile) PSH according to results of 2 polygenic risk scores for systolic and diastolic blood pressure (BP) generated with data on 732 genetic risk variants. A general cognitive ability score was calculated as the first component of an analysis that included the results of 5 cognitive tests. Primary analyses focused on Europeans, and secondary analyses included all race/ethnic groups. RESULTS: Of the 502,422 participants enrolled in the UKB, 48,118 (9.6%) completed the cognitive evaluation, including 42,011 (8.4%) of European ancestry. Multivariable regression models using systolic BP-related genetic variants indicated that compared with study participants with a low PSH, those with intermediate and high PSH had reductions of 3.9% (ß -0.039, SE 0.012) and 6.6% (ß -0.066, SE 0.014), respectively, in their general cognitive ability score (p < 0.001). Secondary analyses including all race/ethnic groups and using diastolic BP-related genetic variants yielded similar results (p < 0.05 for all tests). Analyses evaluating each cognitive test separately indicated that reaction time, numeric memory, and fluid intelligence drove the association between PSH and general cognitive ability score (all individual tests, p < 0.05). DISCUSSION: Among nondemented, community-dwelling, middle-aged Britons, a higher PSH is associated with worse cognitive performance. These findings suggest that genetic predisposition to hypertension influences brain health in persons who have not yet developed dementia. Because information on genetic risk variants for elevated BP is available long before the development of hypertension, these results lay the foundation for further research focused on using genomic data for the early identification of high-risk middle-aged adults.

Suboptimal Sleep Duration is Associated with Poorer Neuroimaging Brain Health Profiles.

Background: Cardiovascular health optimization during middle age benefits brain health. The American Heart Association's Life's Simple 7 recently added sleep duration as a key determinant of cardiovascular health becoming the Life's Essential 8. We tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults. Methods: We conducted a prospective MRI neuroimaging study in middle-aged persons without stroke, dementia, or multiple sclerosis enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers of brain health included white matter hyperintensities (presence and volume) and diffusion tensor imaging metrics (fractional anisotropy and mean diffusivity) evaluated in 48 distinct neuroanatomical regions. We used multivariable logistic and linear regression models, as appropriate, to test for association between sleep duration and neuroimaging markers of brain health. Results: We evaluated 39,502 middle-aged persons (mean age 55, 53% female). Of these, 28,712 (72.7%) had optimal, 8,422 (21.3%) short, and 2,368 (6%) long sleep. Compared to optimal sleep, short sleep was associated with higher risk (OR 1.11; 95% CI 1.05-1.17; P<0.001) and larger volume (beta=0.06, SE=0.01; P<0.001) of white matter hyperintensities, while long sleep was associated with higher volume (beta=0.04, SE=0.02; P=0.01) but not higher risk (P>0.05) of white matter hyperintensities. Short (beta=0.03, SE=0.01; P=0.004) and long sleep (beta=0.07, SE=0.02; P<0.001) were associated with worse fractional anisotropy, while only long sleep associated with worse mean diffusivity (beta=0.05, SE=0.02; P=0.005). Conclusions: Among middle-aged adults without clinically observed neurological disease, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because the evaluated neuroimaging markers precede stroke and dementia by several years, our findings support early interventions aimed at correcting this modifiable risk factor.

Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors.

BACKGROUND AND OBJECTIVES: Blood pressure (BP) is often not at goal in stroke survivors, leaving individuals vulnerable to additional vascular events. Given that BP is a highly heritable trait, we hypothesize that a higher polygenic susceptibility to hypertension (PSH) leads to worse BP control in stroke survivors. METHODS: We conducted a study within the UK Biobank evaluating persons of European ancestry who survived an ischemic or hemorrhagic stroke. To model the PSH, we created polygenic risk scores (PRSs) for systolic and diastolic BP using 732 genetic variants. We divided the PRSs into quintiles and used linear/logistic regression to test whether higher PSH led to higher observed BP, uncontrolled BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg), and resistant BP (uncontrolled BP despite being on ≥3 antihypertensive drugs). We conducted an independent replication using data from the Vitamin Intervention for Stroke Prevention (VISP) trial. RESULTS: We analyzed 5,940 stroke survivors. When comparing stroke survivors with very low vs very high PSH, the mean systolic BP was 137 (SD 18) vs 143 (SD 20, p < 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11, p < 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% (p < 0.001), and the prevalence of resistant hypertension was 3.9% vs 11% (p < 0.001). Results remained significant using multivariable models (p < 0.001) and were replicated in the VISP study (all tests with p < 0.05). DISCUSSION: A higher PSH is associated with worse BP control in stroke survivors. These findings point to genetic predisposition as an important determinant of poorly controlled BP in this population.

Development and Validation of a Model to Identify Critical Brain Injuries Using Natural Language Processing of Text Computed Tomography Reports.

Importance: Clinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings. Objective: To automatically extract acute brain pathological data and their features from head CT reports. Design, Setting, and Participants: This diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021. Main Outcomes and Measures: Performance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets. Results: A total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%. Conclusions and Relevance: These findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma.

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of sCD74 was observed primarily in melanoma cell lines as well as a THP-1 line of macrophages from monocytes and primary macrophages, especially in response to interferon-γ (IFN-γ). A predominant form that showed clinical relevance was the 25-KDa sCD74, which originated from the 33-KDa isoform of CD74. The release of this sCD74 was regulated by either a disintegrin and metalloproteinase-mediated cell-surface cleavage or cysteine-protease-mediated lysosomal cleavage, depending on cell types. Both recombinant and THP-1 macrophage-released endogenous sCD74 suppressed melanoma cell growth and induced apoptosis under IFN-γ stimulatory conditions via inhibiting the MIF/CD74/AKT-survival pathway. Our findings demonstrate that the interplay between sCD74 and MIF regulates tumor progression and determines patient outcomes in advanced melanoma.

Cell-free plasma microRNAs that identify patients with glioblastoma.

Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.

Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.

We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Efficacy of i3.1 Probiotic on Improvement of Lactose Intolerance Symptoms: A Randomized, Placebo-controlled Clinical Trial.

GOAL: The aim of this study was to assess the efficacy of probiotic i3.1 in improving lactose intolerance symptoms compared with placebo after 8 weeks of treatment. BACKGROUND: Probiotics are promising strategies to prevent and improve lactose intolerance symptoms, but previous studies have provided conflicting results. MATERIALS AND METHODS: This randomized, prospective, placebo-controlled study was conducted at the Hospital Juárez de México. We recruited adult patients with lactose intolerance confirmed by a lactose hydrogen breath test (LHBT) ≥20 parts per million (ppm) and a lactose intolerance symptom score ≥6 both upon lactose challenge. We compared the change from baseline in the scores of a validated symptom questionnaire and the LHBT after 8 weeks of probiotic or placebo treatment. RESULTS: We included 48 patients: 33 receiving the probiotic and 15 receiving placebo (2:1 randomization). Demographic characteristics were homogeneous between groups. The reduction in total symptom score after a lactose challenge was significantly higher in the probiotic group versus the placebo group (-5.11 vs. -1.00; P<0.001). All the subscores significantly decreased from baseline in the probiotic group, except for vomiting, with significant differences between the probiotic and placebo groups for abdominal pain (P=0.045) and flatulence (P=0.004). The area under the curve of the LHBT was significantly reduced from baseline in the probiotic group (P=0.019), but differences between groups were not significant (P=0.621). Adverse events were mild without differences between groups, and no serious adverse event was registered. CONCLUSION: The i3.1 probiotic was safe and efficacious in reducing lactose intolerance symptoms in patients with lactose intolerance, but did not change the LHBT.

Early head CT in post-cardiac arrest patients: A helpful tool or contributor to self-fulfilling prophecy?

OBJECTIVE: Neuroprognostication guidelines suggest that early head computed tomography (HCT) might be useful in the evaluation of cardiac arrest (CA) patients following return of spontaneous circulation. We aimed to determine the impact of early HCT, performed within the first 6 h following CA, on decision-making following resuscitation. METHODS: We identified a cohort of initially unconscious post-CA patients at a tertiary care academic medical center from 2012 to 2017. Variables pertaining to demographics, CA details, post-CA care, including neuroimaging and neurophysiologic testing, were abstracted retrospectively from the electronic medical records. Changes in management resulting from HCT findings were recorded. Blinded board-certified neurointensivists adjudicated HCT findings related to hypoxic-ischemic brain injury (HIBI) burden. The gray-white matter ratio (GWR) was also calculated. RESULTS: Of 302 patients, 182 (60.2%) underwent HCT within six hours of CA (early HCT group). Approximately 1 in 4 early HCTs were abnormal (most commonly HIBI changes; 78.7%, n = 37), which resulted in a change in management in nearly half of cases (46.8%, n = 22). The most common changes in management were de-escalation in care [including transition to do not resuscitate status), withholding targeted temperature management, and withdrawal of life sustaining therapy (WLST)]. In cases with radiographic HIBI, mean [standard deviation] GWR was lower (1.20 [0.10] vs 1.30 [0.09], P < 0.001) and progression to brain death was higher (44.4% vs 2.9%; P < 0.001). The inter-rater reliability (IRR) of early HCT to determine presence of HIBI between radiology and three neurointensivists had a wide range (κ 0.13-0.66). CONCLUSION: Early HCT identified abnormalities in 25% of cases and frequently influenced therapeutic decisions. Neuroimaging interpretation discrepancies between radiology and neurointensivists are common and agreement on severity of HIBI on early HCT is poor (k 0.11).

Management of small intestinal bacterial overgrowth by pediatric gastroenterologists in Spain.

BACKGROUND: small intestinal bacterial overgrowth (SIBO) is a heterogeneous condition with nonspecific symptoms. This study aimed to report its management by pediatric gastroenterologists in Spain. METHODS: a descriptive study was performed by means of a survey sent to 184 active members of the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP). RESULTS: one hundred and forty-eight responses (80.4 %) were received. Forty-four patients had no predisposing condition, 31.1 % used antibiotics followed by probiotics, 33.1 % antibiotherapy concomitant with probiotics, 24.3 % only antibiotics and 10.8 % only probiotics. The diagnosis was established via clinical parameters in 73.8 % of participants and the therapeutic response was checked only by clinical data in 90 %. CONCLUSIONS: there is high variability in the management of SIBO among pediatric population in Spain.

Combination of a Probiotic and an Antispasmodic Increases Quality of Life and Reduces Symptoms in Patients with Irritable Bowel Syndrome: A Pilot Study.

BACKGROUND: Probiotics and antispasmodics have been tested extensively in the management of symptoms of irritable bowel syndrome (IBS), but they have rarely been evaluated in combination. The objective of this pilot study was to assess the efficacy of treatment with the probiotic formulation i3.1 (Lactobacillus plantarum CECT7484 and CECT7485 and Pediococcus acidilactici CECT7483), with or without the addition of the antispasmodic alverine/simethicone, in improving IBS-related quality of life (QoL) and reducing abdominal pain and diarrhea in patients with IBS. METHODS: This was a randomized, placebo-controlled clinical trial with 3 parallel arms (probiotic, probiotic plus antispasmodic, and placebo). Patients with IBS (N = 55) were recruited at the Gastroenterology Department of the Juárez Hospital (México City). QoL was assessed with the IBS-QoL questionnaire, abdominal pain with a visual analog scale, and stool consistency with the Bristol scale. RESULTS: The IBS-QoL rate of response (ITT analysis) was 50.0% for patients in the group with probiotic alone, 68.4% in the group with probiotic plus antispasmodic, and 16.7% in the group with placebo after 6 weeks of treatment (p = 0.005). Response to abdominal pain was reported by 38.9% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.035). Regarding stool consistency, a response to treatment was reported by 44.4% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.032). CONCLUSION: The results are consistent with previous studies on the use of the i3.1 probiotic formulation for the management of symptoms in IBS patients, and the addition of an antispasmodic improves its observed effects.