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In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics., Competing Interests: Competing interests: Ben Busby is a full-time employee of DNAnexus. Rebecca Lowdon is a full-time employee of Bayer Crop Sciences. Ramanandan Prabhakaran is a full-time employee of Hoffmann-La Roche Limited. Luis F Paulin is sponsored by Genentech, Inc. Wouter De Coster has received travel reimbursement and free consumables from ONT. FJS received research support from ONT and PacBio. Alejandro Rafael Gener is an editorial board member of AIDS, and has received poster bursaries from ONT in 2019., (Copyright: © 2022 Walker K et al.)

Pretruncal (perimesencephalic) non-aneurysmal subarachnoid hemorrhage (PNSAH) is uniformly associated with an excellent outcome. Although cerebral vasospasm remains a common complication of SAH and constitutes an important predictor of outcome, in the setting of PNSAH, it is extremely rare. Preturnal non-aneurysmal subarac refers to a subset of SAH patients with a characteristic pattern of localized blood on CT of the head, normal cerebral angiography, and benign course when compared to the aneurysmal SAH population. The presence of radiological or even clinical vasospasm does not exclude the diagnosis of PNSAH. To our knowledge, this is the first case of symptomatic cerebral vasospasm due to PNSAH that responded to milrinone.

Background: Brain-body associations are essential in influencing outcome in patients with ruptured brain aneurysms. Thus far, there is scarce literature on such important relationships., Methods: The multicenter Tirilazad database (3551 patients) was used to create this clinical outcome prediction model in order to elucidate significant brain-body associations. Traditional binary logistic regression models were used., Results: Binary logistic regression main effects model included four statistically significant single prognostic variables, namely, neurological grade, age, stroke, and time to surgery. Logistic regression models demonstrated the significance of hypertension and liver disease in development of brain swelling, as well as the negative consequences of seizures in patients with a history of myocardial infarction and post-admission fever worsening neurological outcome., Conclusions: Using the aforementioned results generated from binary logistic regression models, we can identify potential patients who are in the high risk group of neurological deterioration. Specific therapies can be tailored to prevent these detriments, including treatment of hypertension, seizures, early detection and treatment of myocardial infarction, and prevention of hepatic encephalopathy.

Background: Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH)., Methods: The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months., Results: Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P < 0.01)., Conclusions: A clinically useful classification tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.

Background: Endovascular therapy is favored for ruptured intracranial aneurysms in the elderly. However, poor accessibility to the aneurysm through the parent artery and use of local anesthesia in this age group may predispose to intraprocedural complications., Objective: To evaluate whether age-related poor access to the ruptured target aneurysm and use of local anesthesia are associated with increased incidence of procedure-related rupture during endovascular embolization., Methods: A total of 117 patients with 117 ruptured aneurysms underwent endovascular embolization at a single institution. Correlation of increasing age with poor accessibility of the guiding catheter was analyzed. In addition, the distance from the aneurysm to the guiding catheter was investigated to identify an association with incidence of procedure-related rupture. Correlation of local anesthesia with procedure-related rupture was also evaluated in the multivariable analysis., Results: Increasing age was significantly associated with poor accessibility of the guiding catheter (P = .001, Mann-Whitney U test). Procedure-related rupture occurred in 9 of 117 aneurysms (7.7%). Longer distance between distal aneurysms and low-positioned guiding catheters carried a higher risk of procedure-related rupture than a shorter distance between proximal aneurysms and high-positioned guiding catheters (odds ratio, 19.3; 95% confidence interval, 1.84-201; P = .01, multivariable analysis). Use of local anesthesia was also a significant risk factor of procedure-related rupture by multivariable analysis., Conclusion: Increasing age was correlated with poor accessibility of the guiding catheter in endovascular embolization of ruptured intracranial aneurysms. Distally located aneurysms treated through a low-positioned guiding catheter and use of local anesthesia increased the risk of procedure-related rupture.

Object: Intrasylvian hematoma (ISH) is a subtype of intracranial hematoma caused by aneurysmal rupture and often presents with a poor initial neurological grade; it is not well studied. The aim of this study was to elucidate outcomes of aneurysmal subarachnoid hemorrhage (SAH) with ISH., Methods: Data for 97 patients with poor-grade SAH (World Federation of Neurosurgical Societies Grade IV or V) were retrospectively analyzed from a single-center, prospective, observational cohort database. Ultra-early surgical clipping, removal of hematoma, external decompression for brain swelling, and prevention of vasospasm by cisternal irrigation with milrinone were combined as an aggressive treatment. Characteristics and clinical courses of SAH with ISH were identified. The authors also evaluated any correlations between poor admission-grade SAH and ISH with good functional outcome., Results: Patients with poor admission-grade SAH and with ISH were more likely to have initial cerebral edema (p < 0.001, Mann-Whitney U-test), which significantly resolved overtime (p < 0.001, Mann-Whitney U-test). These patients had a better chance of functional survival (modified Rankin Scale scores of 1-3; OR 5.75; 95% CI 1.36-24.3; p = 0.017) at 6 months after hospital discharge, after adjustment for potential confounders such as younger age and better initial neurological grade by multivariable analysis., Conclusions: ISH predicted good functional recovery from poor-grade aneurysmal SAH.

Background: Patients with ruptured brain aneurysms and aneurysmal subarachnoid hemorrhage suffer neurological damage from primary injury of the aneurysm rupture itself, as well as a number of secondary injurious processes that can further worsen the affected individual's neurological state. In addition, other body systems can be affected in a number of brain-body associations., Methods: This systematic review synthesizes prospective and retrospective cohort studies that investigate brain-body associations in patients with ruptured brain aneurysms. The methodologic quality of these studies will be appraised., Results: Six cohort studies were included in this systemic review. The methodologic quality of each study was assessed. They had representative patient populations, clear selection criteria and clear descriptions of study designs. Reproducible study protocols with ethics board approval were present. Clinical results were described in sufficient detail and were applicable to aneurysmal subarachnoid hemorrhage patients in clinical practice. There were few withdrawals from the study. Limitations included small sample sizes and between-study differences in diagnostic tests and clinical outcome endpoints. Several pathophysiologic mechanisms of brain-body associations in ruptured brain aneurysms were clarified through this systematic review. Sympathetic activation of the cardiovascular system in aneurysmal subarachnoid hemorrhage not only triggers the release of atrial and brain natriuretic peptides it can also lead to increased pulmonary venous pressures and permeability causing hydrostatic pulmonary edema. Natriuretic states can herald the onset or worsening of clinical vasospasm as the renin-angiotensin-aldosterone system is activated in a delayed manner., Conclusions: This systematic review synthesizes the most current evidence of underlying mechanisms of brain related associations with body systems in aneurysmal subarachnoid hemorrhage. Results gained from these studies are clinically useful and shed light on how ruptured brain aneurysms affect the cardiopulmonary system. Subsequent neuro-cardio-endocrine responses then interact with other body systems as part of the secondary responses to primary injury.

Background: Clinical prediction tools assist in clinical outcome prediction. They quantify the relative contributions of certain variables and condense information that identifies important indicators or predictors to a targeted condition. This systematic review synthesizes and critically appraises the methodologic quality of studies that derive both clinical predictors and clinical predictor tools used to determine outcome prognosis in patients suffering from aneurysmal subarachnoid hemorrhage (SAH)., Methods: This systematic review included prospective and retrospective cohort studies, and randomized controlled trials (RCTs) investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adult patients with aneurysmal SAH., Results: Twenty-two studies were included in this systemic review. Independent, confounding, and outcome variables were studied. Methodologic quality of individual studies was also analyzed. Included were 3 studies analyzing databases from RCTs, 8 prospective cohort studies, and 11 retrospective cohort studies. The most frequently retained significant clinical prognostic factors for long-term neurologic outcome prediction include age, neurological grade, blood clot thickness, and aneurysm size., Conclusions: Systematic reviews for clinical prognostic factors and clinical prediction tools in aneurysmal SAH face a number of methodological challenges. These include within and between study patient heterogeneity, regional variations in treatment protocols, patient referral biases, and differences in treatment, and prognosis viewpoints across different cultures.

Background: While clipping cerebral aneurysms at the neck is optimal, in some cases this is not possible and other strategies are necessary. The purpose of this study was to describe the incidence, risk factors, and outcomes for inability to clip reconstruct ruptured anterior communicating artery (ACoA) aneurysms., Methods: Of the 70 cases of ruptured ACoA aneurysms between January 2006 and December 2013, our institutional experience revealed four cases of small ACoA aneurysms that had been considered clippable prior to operation but required trapping. When a unilateral A2 segment of anterior cerebral artery (ACA) was compromised by trapping, revascularization was performed by bypass surgery. Clinical presentation, angiographic characteristics, operative approach, intraoperative findings, and treatment outcomes were assessed., Results: Very small aneurysm under 3 mm was a risk factor for unexpected trapping. The reason for unexpected trapping was laceration of the aneurysmal neck in two cases, and lack of clippaple component due to disintegration of entire aneurysmal wall at the time of rupture in the others. Aneurysms with bilateral A1 were treated with sole trapping through pterional approach in two cases. The other two cases had hypoplastic unilateral A1 segment of ACA and were treated with combination of aneurysm trapping and revascularization of A2 segment of ACA through interhemispheric approach. No patients had new cerebral infarctions of cortical ACA territory from surgery. Cognitive dysfunction was observed in three cases, but all patients became independent at 12-month follow up., Conclusions: Unexpected trapping was performed when ruptured ACoA aneurysms were unclippable. Trapping with or without bypass can result in reasonable outcomes, with acceptable risk of cognitive dysfunction.

Object: The goal of this study was to determine racial/ethnic differences in inpatient mortality rates and the use of institutional postacute care following subarachnoid hemorrhage (SAH) in the U.S., Methods: A cross-sectional study of hospital discharges for SAH was conducted using the Nationwide Inpatient Sample for the years 2005-2010. Discharges with a principal diagnosis of SAH were identified and abstracted using the appropriate ICD-9-CM diagnostic code. Racial/ethnic groups were defined as white, black, Hispanic, Asian/Pacific Islander (API), and American Indian. Multinomial logistic regression analyses were performed comparing racial/ethnic groups with respect to the primary outcome of risk of in-hospital mortality and the secondary outcome of likelihood of discharge to institutional care., Results: During the study period, 31,631 discharges were related to SAH. Race/ethnicity was a significant predictor of death (p = 0.003) and discharge to institutional care (p ≤ 0.001). In the adjusted analysis, compared with white patients, API patients were at higher risk of death (OR 1.34, 95% CI 1.13-1.59) and Hispanic patients were at lower risk of death (OR 0.84, 95% CI 0.72-0.97). The likelihood of discharge to institutional care was statistically similar between white, Hispanic, API, and Native American patients. Black patients were more likely to be discharged to institutional care compared with white patients (OR 1.27, 95% CI 1.14-1.40), but were similar to white patients in the risk of death., Conclusions: Significant racial/ethnic differences are present in the risk of inpatient mortality and discharge to institutional care among patients with SAH in the US. Outcome is likely to be poor among API patients and best among Hispanic patients compared with other groups.

Introduction: This systematic review and meta-analysis aimed to evaluate the effect of small bowel feeding compared with gastric feeding on the frequency of pneumonia and other patient-important outcomes in critically ill patients., Methods: We searched EMBASE, MEDLINE, clinicaltrials.gov and personal files from 1980 to Dec 2012, and conferences and proceedings from 1993 to Dec 2012 for randomized trials of adult critically ill patients in the intensive care unit (ICU) comparing small bowel feeding to gastric feeding, and evaluating risk of pneumonia, mortality, length of ICU stay, achievement of caloric requirements, duration of mechanical ventilation, vomiting, and aspiration. Independently, in duplicate, we abstracted trial characteristics, outcomes and risk of bias., Results: We included 19 trials with 1394 patients. Small bowel feeding compared to gastric feeding was associated with reduced risk of pneumonia (risk ratio [RR] 0.70; 95% CI, 0.55, 0.90; P = 0.004; I2 = 0%) and ventilator-associated pneumonia (RR 0.68; 95% CI 0.53, 0.89; P = 0.005; I2 = 0%), with no difference in mortality (RR 1.08; 95% CI 0.90, 1.29; P = 0.43; I2 = 0%), length of ICU stay (WMD -0.57; 95%CI -1.79, 0.66; P = 0.37; I2 = 0%), duration of mechanical ventilation (WMD -1.01; 95%CI -3.37, 1.35; P = 0.40; I2 = 17%), gastrointestinal bleeding (RR 0.89; 95% CI 0.56, 1.42; P = 0.64; I2 = 0%), aspiration (RR 0.92; 95% CI 0.52, 1.65; P = 0.79; I2 = 0%), and vomiting (RR 0.91; 95% CI 0.53, 1.54; P = 0.72; I2 = 57%). The overall quality of evidence was low for pneumonia outcome., Conclusions: Small bowel feeding, in comparison with gastric feeding, reduces the risk of pneumonia in critically ill patients without affecting mortality, length of ICU stay or duration of mechanical ventilation. These observations are limited by variation in pneumonia definition, imprecision, risk of bias and small sample size of individual trials.

Objective: The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH)., Methods: The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients)., Results: Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters., Discussion: This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication.

Context: New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile., Objective: To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent. Study Selection & Data Extraction: Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data., Results: Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects., Conclusions: Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.

Object: Cephaloceles represent primary axial mesodermal defects, occurring in 0.8-4 per 10,000 live births. Prior studies have reported posterior location, hydrocephalus, microcephaly, seizure, and presence of brain tissue as poor prognostic markers for neurological outcome. However, these studies were small and the results were analyzed using univariate tests. The purpose of this study was to investigate the potential risk factors for the occurrence of developmental delay in patients with cephaloceles, using both univariate and multivariable regression techniques., Methods: This is a retrospective cohort study of cephalocele cases treated at the Hospital for Sick Children between 1990 and 2006. Two independent investigators collected the data from the Hospital for Sick Children Encephalocele Database and hospital charts. Developmental assessments were made by general pediatricians and neuropsychologists. Both univariate analysis (alpha=0.10) and multivariable logistic regression analysis (alpha=0.05) were performed., Results: Eighty-five cases of cephaloceles were identified. The patient group consisted of 48 boys and 37 girls. Sixty-eight lesions were encephaloceles and 17 were meningoceles. The distribution was as follows: frontal (40 lesions), occipital (33), and parietal (12). Associated conditions included hydrocephalus (23), seizure disorder (17), microcephaly (6), corpus callosal abnormalities (15), heterotopias (9), cerebral dysgenesis (11), and myelomeningocele (1). Evaluation of long-term development revealed that 41 patients (48%) had normal development, 9 (11%) had mild delay, 14 (16%) had moderate delay, and 21 (25%) had severe delay. Hydrocephalus, seizure disorder, microcephaly, presence of associated intracranial abnormalities, and presence of brain tissue were significantly associated with poor outcome on univariate analysis. Multivariable analysis revealed hydrocephalus and presence of intracranial abnormalities to be statistically significant predictors of developmental delay., Conclusions: To the authors' knowledge, this is one of the largest North American cephalocele series documented. Unlike prior studies, location of the cephaloceles is not a significant predictor of outcome. The multivariable regression analysis demonstrates hydrocephalus and the presence of associated intracranial abnormalities as variables with cumulative predictive effects for developmental delay.