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
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.
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;
<0.001), larger WMH volume (beta=0.06 95% CI, 0.04-0.08;
<0.001), and worse fractional anisotropy profiles (beta=-0.04 95% CI, -0.06 to -0.02;
=0.001). Compared with optimal sleep, long sleep duration was associated with larger WMH volume (beta=0.04 95% CI, 0.01-0.08;
=0.02) and worse fractional anisotropy profiles (beta=-0.06 95% CI, -0.1 to -0.02;
=0.002), but not with WMH presence (
=0.6).
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.
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.
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.
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).
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).
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.
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.
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% (β -0.039, SE 0.012) and 6.6% (β -0.066, SE 0.014), respectively, in their general cognitive ability score (
< 0.001). Secondary analyses including all race/ethnic groups and using diastolic BP-related genetic variants yielded similar results (
< 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,
< 0.05).
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.
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.
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.
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,
< 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11,
< 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% (
< 0.001), and the prevalence of resistant hypertension was 3.9% vs 11% (
< 0.001). Results remained significant using multivariable models (
< 0.001) and were replicated in the VISP study (all tests with
< 0.05).
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.
Abstract
The activity of neuron populations gives rise to field potentials (FPs) that extend beyond the sources. Their mixing in the volume dilutes the original temporal motifs in a site-dependent ...manner, a fact that has received little attention. And yet, it potentially rids of physiological significance the time-frequency parameters of individual waves (amplitude, phase, duration). This is most likely to happen when a single source or a local origin is erroneously assumed. Recent studies using spatial treatment of these signals and anatomically realistic modeling of neuron aggregates provide convincing evidence for the multisource origin and site-dependent blend of FPs. Thus, FPs generated in primary structures like the neocortex and hippocampus reach far and cross-contaminate each other but also, they add and even impose their temporal traits on distant regions. Furthermore, both structures house neurons that act as spatially distinct (but overlapped) FP sources whose activation is state, region, and time dependent, making the composition of so-called local FPs highly volatile and strongly site dependent. Since the spatial reach cannot be predicted without source geometry, it is important to assess whether waveforms and temporal motifs arise from a single source; otherwise, those from each of the co-active sources should be sought.
Background All of Us is a novel research program that aims to accelerate research in populations traditionally underrepresented in biomedical research. Our objective was to evaluate the burden of ...cardiovascular disease (CVD) in broadly defined underrepresented groups. Methods and Results We evaluated the latest data release of All of Us. We conducted a cross-sectional analysis combining survey and electronic health record data to estimate the prevalence of CVD upon enrollment in underrepresented groups defined by race, ethnicity, age (>75 years), disability (not able to carry out everyday physical activities), sexual orientation and gender identity lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+), income (annual household income <$35 000 US dollars) and education (less than a high school degree). We used multivariate logistic regression to estimate the adjusted odds ratio (OR) and product terms to test for interaction. The latest All of Us data release includes 315 297 participants. Of these, 230 577 (73%) had information on CVD and 17 958 had CVD (overall prevalence, 7.8%; 95% CI, 7.7-7.9). Multivariate analyses adjusted by hypertension, hyperlipidemia, type 2 diabetes mellitus, body mass index, and smoking indicated that, compared with White participants, Black participants had a higher adjusted odds of CVD (OR, 1.21; 95% CI, 1.16-1.27). Higher adjusted odds of CVD were also observed in underrepresented groups defined by other factors, including age >75 years (OR, 1.90; 95% CI, 1.81-1.99), disability (OR, 1.60; 95% CI, 1.53-1.68), and income <$35 000 US dollars (OR, 1.22; 95% CI, 1.17-1.27). Sex significantly modified the odds of CVD in several of the evaluated groups. Conclusions Among participants enrolled in All of Us, underrepresented groups defined based on race, ethnicity and other factors have a disproportionately high burden of CVD. The All of Us research program constitutes a powerful platform to accelerate research focused on individuals in underrepresented groups.
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association ...between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.
Background
The gut microbiota, composed by several species of microorganisms, works to preserve the liver–gut homeostasis and plays an important role during digestion and absorption of nutrients, and ...in the immune response of the host. In this review, we analyzed the influence of microbiota in patients with cholangiocarcinoma (CCA) who were candidates for elective surgery.
Methods
A literature review was conducted to identify papers that provided empiric evidence to support that the altered microbiota composition (dysbiosis) is related also to CCA development.
Results
Bacteria such as
Helicobacter pylori
,
Helicobacter hepaticus
, and
Opisthorchis viverrini
increase the risk of CCA. The most abundant genera were Enterococcus, Streptococcus, Bacteroides, Klebsiella, and Pyramidobacter in CCA’s biliary microbiota. Additionally, levels of Bacteroides, Geobacillus, Meiothermus, and Anoxybacillus genera were significantly higher. An enrichment of Bifidobacteriaceae, Enterobacteriaceae, and Enterococcaceae families has also been observed in CCA tumor tissue. Microbiota is related to postoperative outcomes in abdominal surgery. The combination of caloric restriction diets in liver cancer or CCA increases the effect of the chemotherapy treatment.
Conclusion
The correct use of nutrition for microbiota modulation according to each patient’s needs could be a therapeutic tool in combination with elective surgery and chemotherapy to diminish side effects and improve prognosis. Further investigations are needed to fully understand the mechanisms by which they are related.
BACKGROUND AND PURPOSE—Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the ...paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort.
METHODS—We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4–6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed.
RESULTS—We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66–1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59–1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location.
CONCLUSIONS—Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.
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