Influence Of Etiology Research Articles

The Etiological and Predictive Association Between ADHD and Cognitive Performance From Childhood to Young Adulthood

Objective: Evidence about the etiology of the predictive associations between a diagnosis of ADHD and cognitive performance over time is scarce. Here, we examine these predictive and etiological patterns using a cross-lagged model design in a sample of 404 participants (74% males) from ADHD and control sibling pairs aged 6 to 17 years at baseline and 12 to 24 years at follow-up. Methods: Data included IQ, short-term and working memory measures, and response speed and variability from a four-choice reaction-time task. Results: ADHD and IQ predicted each other over time. ADHD at baseline predicted lower working memory performance at follow-up. Stable etiological influences emerged in the association between ADHD and cognitive variables across time. Conclusion: Whether early interventions can reduce negative interference with learning at school requires further study.

Etiology of end-stage liver cirrhosis impacts hepatic natural killer cell heterogenicity.

The natural killer (NK) cell population is a critical component of the innate immune compartment of the liver, and its functions are deeply affected by the surrounding environment. In the late stage of fibrosis, NK cells become dysfunctional, but the influence of disease etiology on NK cell behavior during cirrhosis remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterized the hepatic NK cells from end-stage cirrhotic livers from subjects with non-alcoholic steatohepatitis (NASH), chronic hepatitis C infection (HCV) and primary sclerosing cholangitis (PSC). Here, we show that although NK cells shared similar dysfunctions, the disease etiology impacts hepatic NK cell heterogeneity. Therapeutical strategies targeting NK cells for the prevention or treatment of fibrosis should consider liver disease etiology in their design.

“Functional outcomes and MRI-based tendon healing after (antero-) superior rotator cuff repair among patients under 50 years: retrospective analysis of traumatic versus non-traumatic rotator cuff tears”

BackgroundRotator cuff tears among patients under 50 years either result from an adequate trauma or are considered non-traumatic due to work-related or athletic overuse. The impact of these different mechanisms on postoperative functional outcomes and tendon healing has not yet been fully understood. Therefore, it was the purpose of this study to investigate the influence of etiology of (antero-)superior rotator cuff tears on postoperative outcomes and the healing rates after arthroscopic rotator cuff repair in a young patient population.MethodsPatients under 50 years who underwent arthroscopic rotator cuff repair between 2006–2017 for an anterosuperior rotator cuff tear with a minimum follow up of 24 months were included in this study. Revision surgeries or reconstructive concomitant procedures other than long head of the biceps tenodesis were excluded. Patients were divided into two groups according to the etiology of their rotator cuff tear (traumatic vs. non-traumatic). Demographic and outcome scores including the American Shoulder and Elbow Surgeons (ASES) score, the Constant Score (CS), bilateral strength measurements and postoperative tendon integrity evaluated on magnetic resonance imaging (MRI) were assessed and compared between both groups.ResultsThe mean follow up for this study was 55.6 months (24 – 158). Twenty-one patients (50.0%) had a traumatic RCT and 21 patients (50.0%) had a non-traumatic tear. Outcome scores did not differ significantly between groups. Strength measurements of the supraspinatus revealed significantly decreased force of the affected side as opposed to the contralateral side (p = 0.001), regardless of etiology. Retear rates were similar in both groups (37.5% and 33.3%, p = n.s.). Cuff integrity at follow-up was not predictive of superior scores or strength.ConclusionSurgical treatment of traumatic and non-traumatic RCT yields good clinical results in patients under the age of 50. The etiology of the rotator cuff tear did not significantly affect postoperative outcomes or healing rates. About one third of the patients suffered from a retear postoperatively, however retears were not predictive of inferior outcomes at midterm follow-up.Study designLevel III.Trial registrationRetrospectively registered.

Psychological distress in pulmonary embolism survivors in a pulmonary embolism response team clinic: Protocol for a prospective observational study

BackgroundPulmonary embolism (PE) is a leading cause of cardiovascular death. Psychological distress in PE is understudied and underrecognized. ObjectivesThe primary aim of this proposed protocol was to describe the incidence of psychological distress symptoms (anxiety, depression, posttraumatic stress, and fear of recurrence) in the survivors of PE after discharge from hospitalization. The secondary aim was to assess the influence of acute disease, etiology, and treatment of PE on psychological distress. MethodsThis is a prospective observational cohort study in a large tertiary care referral center. The participants are adult patients presenting to the hospital with PE fulfilling objective pulmonary embolism response team (PERT) activation criteria. After discharge, patients complete a series of validated measures of psychological distress (anxiety, depression, posttraumatic stress, and fear of recurrence) and quality of life at follow-ups approximately 1, 3, 6, and 12 months after diagnosis and treatment of their PE. Factors influencing each type of distress are evaluated. ConclusionThis protocol aims to identify the unmet needs of patients experiencing psychological distress following PE. It will describe anxiety, depression, fear of recurrence, and posttraumatic symptoms in PE survivors during the first year of outpatient follow-up in a PERT clinic.

Immunotherapy in hepatocellular carcinoma: How does underlying liver disease influence therapeutic strategy and outcomes?

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with up to 90% of HCC cases occurring in the setting of underlying cirrhosis. Therapeutic landscape for advanced HCC has dramatically changed in recent years with the advent of immunotherapy, including several combinations. Data suggest that the surrounding liver milieu may influence tumour response. In addition, different aetiologies of HCC and their effects on the host liver may impact response to immunotherapy. However, to date, guidelines do not take into account this parameter to guide therapeutic selection, and phase III trials are likewise performed in patients irrespective of HCC aetiology. Moreover, most clinical trial data are collected in highly selected patients with preserved liver function (defined as Child-Pugh class A) and controlled portal hypertension, which does not accurately reflect routine clinical practice. In this review, we discuss the influence of liver disease aetiology on the response to immunotherapy in patients with advanced HCC. We also discuss the safety and efficacy of various immunotherapeutic agents in Child-Pugh B patients to determine if these treatments are beneficial in this vulnerable patient population.

Variability of response to exercise‐primed tDCS in those with mild cognitive impairment and Alzheimer’s disease (the EXPRESS study): a preliminary analysis

AbstractBackgroundStudies investigating the use of transcranial direct current stimulation (tDCS) to improve outcomes in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) have reported mixed findings. Such variability may be explained by inter‐individual differences such as demographics or disease pathology. Given the increased prevalence of cardiovascular risk factors with aging and the potential changes in neurobiology of those exhibiting additional vascular etiology, we evaluate the influence of etiology on tDCS outcomes in patients with mild AD or MCI.MethodParticipants were diagnosed with mild or major neurocognitive disorder due to AD or mixed AD/vascular disease according to The Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria. Participants completed a 2‐week, blinded, randomized trial examining the effects of exercise primed tDCS where they were randomized to receive either exercise with tDCS, exercise with sham tDCS, or tDCS only. Cognitive tests assessing episodic memory (ADAS‐Cog Word Recognition and Word Recall Tasks) and working memory (N‐Back) were administered before and after intervention. Independent t‐tests were used to assess for differences in demographics between groups, and paired t‐tests were used to evaluate the influence of etiology on tDCS outcomes.ResultOf the 28 participants (17 males [58.6%], mean [±SD] age 74.8±8.9 years, education 16.3±2.2 years) included, 17 participants had mixed vascular/AD etiology and 11 participants had AD (without vascular) etiology. Both groups did not differ significant in demographics. Participants with mixed vascular/AD etiology showed significant improvement in episodic memory (Word Recognition 1.71±2.97, t(16) = 2.365, p = 0.031; Word Recall 0.65±1.12, t(16) = 2.257, p = 0.038), while those without vascular etiology did not (Word Recognition 0.36±2.80, t(10) = 0.43, p = 0.676; Word Recall ‐0.09±0.63, t(10) = ‐0.472, p = 0.647). No significant improvement in working memory in either group was observed.ConclusionFactors such as etiology should be taken into consideration when considering the efficacy of tDCS on improving cognition in patients diagnosed with AD/MCI. Further analyses upon unblinding will confirm whether patients with mixed AD/vascular etiology respond differently to tDCS.

Genetic versus environmental influences on callous-unemotional traits in preadolescence: The role of parenting and parental psychopathology.

Children with callous-unemotional (CU) traits are at risk for severe conduct problems. While CU traits are moderately heritable, parenting also predicts risk. However, few studies have investigated whether parenting factors (e.g., acceptance, conflict, parental psychopathology) moderate the etiology of CU traits, while accounting for gene-environment correlations. To address this knowledge gap, we used data from 772 twin pairs from the Adolescent Brain and Cognitive Development Study to test bivariate models that explored overlapping etiological influences on CU traits and child reports of their parenting environment. We also used gene-by-environment interaction models to test whether parenting moderated genetic versus environmental influences. There were no overlapping etiological influences on CU traits and parental acceptance, but modest genetic and non-shared environmental overlap between CU traits and family conflict. Parental acceptance and psychopathology moderated non-shared environmental influences, with stronger non-shared environmental influences on CU traits among children who experienced lower parental acceptance and greater parental psychopathology. Family conflict only moderated environmental influences when models did not covary for conduct problems. Parental acceptance and parental psychopathology may be specific environmental protective and risk factors for CU traits, whereas family conflict may represent a general environmental risk factor for both CU traits and conduct problems.

Impact of surgical treatment on parent-reported health related quality of life measures in early-onset scoliosis: stable but no improvement at 2years.

The etiology of early-onset scoliosis (EOS) has been shown to significantly influence baseline parent-reported health-related quality of life (HRQoL) measures as assessed by the Early Onset Scoliosis Questionnaire (EOSQ). We sought to assess the influence of distraction-based surgery and scoliosis etiology on EOSQ 2years following surgical intervention remains unclear. A retrospective review of a multi-center prospective EOS database was performed. Children untreated with distraction-based, growth friendly instrumentation for EOS with completed baseline and 2-year post-surgical EOSQ were included. Children were subdivided by curve etiology individually and in combined cohorts (congenital/idiopathic [C/I], neuromuscular/syndromic [NMS]). EOSQ domains and compositive HRQoL score at presentation and 2-year follow-up were compared across C-EOS etiologies. Minimal clinically important difference (MCID) was defined as ≥ 20% change in domain score and compared across etiologies. 150 children with EOS met inclusion criteria (mean 7.09 ± 2.6years, 58.9% female). There were no differences in EOSQ domains between Congenital vs. Idiopathic nor NM vs. Syndromic etiologies at any timepoint. Combined C/I children demonstrated significantly higher EOSQ scores than combined NMS at initial and 2-years post-treatment. Etiology remained the only independent predictor of 2-year EOSQ composite HRQoL score. Overall, the vast majority of children demonstrated stable HRQoL composite scores, with a trend toward more positive MCID in NMS etiologies. EOS etiology remains the most significant influence on EOSQ scores 2years following surgical intervention. However, the majority of patients, regardless of etiology, maintain stable HRQoL scores suggesting that surgery may only serve to stabilize HRQoL at 2years.

Results of tonic and burst epidural spinal cord stimulation in patients with spasticity, chronic disorders of consciousness and neuropathic pain syndrome at the rehabilitation stage

The paper analyzes the experience of using epidural spinal cord stimulation in tonic and burst stimulation modes in 71 patients with the consequences of damage to the central nervous system, who underwent treatment and rehabilitation at the Research Institute of Rehabilitology named after professor I.V. Pryanikov, FSCC RR, from 2020 to 2021. The efficacy of epidural stimulation in the indicated modes for clinical manifestations of pyramidal syndrome in the extremities, chronic disorders of consciousness, neuropathic pain, and paresis of the extremities without spasticity has been studied. The use of invasive spinal cord stimulation in the burst mode in patients with spasticity and chronic disorders of consciousness is described for the first time. The impact of various factors on the effectiveness of stimulation has also been analyzed. The average age of patients in the study group was 47 ± 17 years, the average duration of test epidural stimulation was 4.3 ± 1.6 days. Twenty-eight patients (39.5%) were stimulated in the tonic mode, twenty-two patients (31%) were stimulated in the burst mode, and the remaining patients were stimulated in the combined mode. Results: positive dynamics after the use of epidural stimulation was observed in 39 patients (54.9%). The spasticity regressed in 32 patients (52.5%); in addition, an increase in the active range of motion was observed in 23 patients (37.7%) from this subgroup. The decrease in the severity of spasticity in the extremities ranged from 0.33 ± 0.1 to 0.63 ± 0.13 points (p<0.005). The signs of an increase in the level of consciousness as a result of the stimulation were noted in 8 patients (38.1%); the neuropathic pain syndrome regressed in 8 patients (72.7%). When applying this technique in patients with paresis without spasticity, the stimulation did not have an effect in any patients of this subgroup. There was no statistically significant influence of etiology, age of patients or duration of stimulation on its effect. The patients with spasticity, who were stimulated in the tonic mode, more often demonstrated the effectiveness of stimulation compared with the patients from the combined mode subgroup (p<0.013). Higher effectiveness of the burst mode stimulation compared to the combined mode stimulation in patients with spasticity was on the borderline of statistical significance (p=0.065). Thus, the use of epidural stimulation in patients with chronic neuropathic pain and spasticity showed the best results; the effect of epidural stimulation on the level of consciousness in chronic disorders requires additional studies and changes in their design.

Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers

Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers

Developmental and etiological patterns of substance use from adolescence to middle age: A longitudinal twin study

BackgroundThe common liability to addiction framework suggests the tendency to use substances is largely a general heritable liability, but little is known about how expression of liability varies across development. We evaluated average developmental trajectories and covariation underlying commonly used substances using a genetically informative prospective design spanning three decades. MethodsUsing a sample of 3762 twins across seven waves of assessment spanning ages 14–40, we modeled these relationships using two complementary approaches: piecewise latent growth and common factor modeling on four measures of alcohol, tobacco, and marijuana use ResultsAverage use increased across adolescence and either stabilized (alcohol frequency) or declined (all others) in adulthood. Trajectories were heritable (~.35–.75), and genetically correlated with one another (~.40–.80). The random intercepts, centered at age 16, exhibited shared environmental correlations across substances. We found moderate to large phenotypic (rp~.3–.9) and genetic correlations (rg~.3–1) among the longitudinally varying common factors loading on use of each substance at each age. The factor loadings declined with age, reflecting waning influence of common etiology in substance use. ConclusionsTrajectories of substance use were strongly correlated with each other and influenced primarily by genetic and non-shared environment. A heritable common factor accounted for co-occurring substance use from mid-adolescence to mid-adulthood, and greater substance specificity emerged with maturation. These results extend and reinforce prior work examining consumption and problem use, providing new evidence over a broad age range showing that substance use behaviors are influenced by a more general liability in adolescence and specificity increases across development.

Ankle Arthritis Etiology Predicts Patterns of Gait Dysfunction: A Prospective Multivariate Gait Analysis

Category:Ankle; Ankle Arthritis; Basic Sciences/Biologics; HindfootIntroduction/Purpose:Preoperative factors influencing functional disability imparted on the patient by ankle arthritis have not previously been assessed with gait analysis. The purpose of this study was to assess the influence of ankle arthritis etiology and deformity, measured radiographically, on gait performance in a dedicated gait lab utilizing a multisegment foot model. With three calcaneal and four metatarsal markers in addition to standard lower extremity markers, the modified Helen Haynes model allows for the evaluation of range of motion (ROM) within the 'ankle-hindfoot segment.' The primary hypothesis was that three- dimensional ankle-hindfoot segment ROM would be more restricted in patients with post-traumatic ankle arthritis than other etiologies. The secondary hypothesis was that temporospatial and kinetic measures would not vary by etiology.Methods:A longitudinal cohort of 183 patients with end-stage ankle arthritis were prospectively enrolled from 2008-2018. Mean age was 61, BMI 29, and 56% were male. Four etiologic groups were defined: Post-fracture (100), arthritis caused by planovalgus foot deformity (23), chronic instability associated with cavovarus (32), and miscellaneous (28), comprised of inflammatory (7), idiopathic (6), instability without deformity (5), septic (2), and avascular necrosis (3) as causes. The four-segment Milwaukee foot model was used in a dedicated gait lab with a 12-camera motion capture system. Gait data was collected over a minimum 20 gait cycles across a 10-meter walkway. Kinetic data was simultaneously collected with two force plates embedded in the walkway operating at 1 MHz. AP and lateral tibiotalar angles, lateral talus-first metatarsal angles, calcaneal pitch, and tibiotalar ratio were measured. Multivariate regression analyzed the effect of etiology and radiographic measures on gait function, controlling for age, gender, and BMI.Results:The primary hypothesis was confirmed. Sagittal plane ankle-hindfoot segment ROM was lower in post-traumatic and higher in valgus patients compared to other etiological groups (P<0.0001) (Figure 1). Sagittal plane ankle-hindfoot segment ROM restriction relative to the contralateral limb was also more severe in the post-traumatic group than others (P=0.0005). Valgus AP tibiotalar angles were associated with greater sagittal plane ankle-hindfoot ROM (P=0.0016). The secondary hypothesis was disproven. Post-traumatic patients ambulate with greater maximum ankle moment than other groups (P=0.0043). Valgus patients ambulate with a comparatively longer step length (P<0.0001). Significant reductions in affected limb walking speed (P<0.0001), step length (P<0.0001), and maximum ankle moment (P=0.036), as well as increases in double limb (P=0.0007) and total support percentage (P<0.0001) were found among the miscellaneous etiology group.Conclusion:Of the four groups, patients with post-traumatic ankle arthritis ambulated with the greatest ankle and hindfoot stiffness, but also the greatest ankle moment. Patients with valgus ankle arthritis had the greatest ROM through the ankle and hindfoot and the longest step length. In addition to diminished ROM, patients in the miscellaneous group had the lowest cadence, symmetry, and torque of gait. The etiology of severe ankle arthritis can predict the pattern of gait dysfunction, which, in turn, may inform choices of surgical reconstruction.

The influence of etiology on surgical outcomes in neovascular glaucoma

BackgroundThe authors sought to evaluate visual outcomes in patients with varying etiologies of neovascular glaucoma (NVG), who were treated with glaucoma drainage devices (GDD).MethodsThis was a retrospective case series of patients at a large academic teaching institution who had surgical intervention for neovascular glaucoma between September 2011 and May 2019. Eyes were included if there was documented neovascularization of the iris/angle with an intraocular pressure (IOP) > 21 mmHg at presentation. Eyes must also have been treated with surgical intervention that included a GDD. Primary outcome measure was visual acuity at the 1-year post-operative visit. Secondary outcome measure was qualified success after surgery defined by: pressure criteria (5 mmHg < IOP ≤ 21 mmHg), no re-operation for elevated IOP, and no loss of LP vision.ResultsOne hundred twenty eyes met inclusion criteria. 61.7% had an etiology of proliferative diabetic retinopathy (PDR), 23.3% had retinal vein occlusions (RVO), and the remaining 15.0% suffered from other etiologies. Of patients treated with GDD, eyes with PDR had better vision compared to eyes with RVO at final evaluation (p = 0.041). There was a statistically significant difference (p = 0.027) in the mean number of glaucoma medications with Ahmed eyes (n = 70) requiring 1.9 medications and Baerveldt eyes (n = 46) requiring 1.3 medications at final evaluation.ConclusionsIn our study, many patients with NVG achieved meaningful vision, as defined by World Health Organization (WHO) guidelines, and IOP control after GDD. Outcomes differed between patients with PDR and RVO in favor of the PDR group. Different GDD devices had similar performance profiles for VA and IOP outcomes. Direct prospective comparison of Baerveldt, Ahmed, and cyclophotocoagulation represents the next phase of discovery.

Stroke Etiology and Outcomes after Endovascular Thrombectomy: Results from the SITS Registry and a Meta-Analysis.

Background and PurposeThe influence of stroke etiology on outcomes after endovascular thrombectomy (EVT) is not well understood. We aimed to investigate whether stroke etiology subgrouped as large artery atherosclerosis (LAA) and cardiac embolism (CE) influences outcomes in large artery occlusion (LAO) treated by EVT. MethodsWe included EVT treated LAO stroke patients registered in the Safe Implementation of Treatment in Stroke (SITS) thrombectomy register between January 1, 2014 and September 3, 2019. Primary outcome was successful reperfusion (modified Treatment in Cerebral Infarction 2b-3). Secondary outcomes were symptomatic intracranial hemorrhage (SICH), 3-month functional independence (modified Ranking Scale 0–2) and death. Multivariable logistic regression models were used for comparisons. In addition, a meta-analysis of aggregate data from the current literature was conducted (PROSPERO, ID 167447). ResultsOf 7,543 patients, 1,903 (25.2%) had LAA, 3,214 (42.6%) CE, and 2,426 (32.2%) unknown, other, or multiple etiologies. LAA patients were younger (66 vs. 74, P<0.001) and had lower National Institutes of Health Stroke Scale score at baseline (15 vs. 16, P<0.001) than CE patients. Multivariable analyses showed that LAA patients had lower odds of successful reperfusion (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.57 to 0.86) and functional independence (OR, 0.74; 95% CI, 0.63 to 0.85), higher risk of death (OR, 1.44; 95% CI, 1.21 to 1.71), but no difference in SICH (OR, 1.09; 95% CI, 0.71 to 1.66) compared to CE patients. The systematic review found 25 studies matching the criteria. The meta-analysis did not find any difference between etiologies. ConclusionsFrom the SITS thrombectomy register, we observed a lower chance of reperfusion and worse outcomes after thrombectomy in patients with LAA compared to CE etiology, despite more favorable baseline characteristics. In contrast, the meta-analysis did not find any difference between etiologies with aggregate data.

Continued root development of immature permanent teeth after regenerative endodontics with or without a collagen membrane: A randomized, controlled clinical trial.

Recent studies evaluated the efficacy of a collagen membrane (Bio-Gide) to promote root development in regenerative endodontics (REPs). However, the influence of etiology and tooth type on the results was not assessed. To evaluate the quantitative and qualitative effect of a collagen membrane (Bio-Gide), with and without the effect of etiology and tooth type, in promoting root development in immature teeth after REPs. Eighty nonvital immature teeth were divided randomly into two groups (40 teeth in each group). REPs were performed with (experimental group) and without (control group) a collagen membrane. All teeth were subjected to regular clinical and radiographical follow-up. Seventy-six teeth were included in the final analyses. The average follow-up periods were 33.1 ± 21.8 months for the control group and 28.1± 18.6 months for the experimental group. Quantitative analysis of root development in the experimental group showed a greater increase in dentin wall thickness in the middle one-third of the root compared to the control group, with or without the effect of etiology and tooth type. Six types of root development were observed. There was no significant difference in the type of tooth development between the two groups. The use of a collagen membrane could promote an increase in dentin wall thickness in the middle one-third of the root, and it had no significant effect in terms of the type of subsequent root development.

Does stroke etiology influence outcome in the posterior circulation? An analysis of 107 consecutive acute basilar occlusion thrombectomies

Acute basilar artery occlusion (BAO) harbors a more guarded prognosis after thrombectomy compared with anterior circulation large-vessel occlusion. Whether this is a function of a greater proportion of atherosclerotic/intrinsic lesions is not well studied. The authors aimed to elucidate the prevalence and predictors of intracranial intrinsic atherosclerotic disease in patients with acute BAO and to compare angiographic and clinical outcomes between patients with BAO secondary to embolic versus intrinsic disease. A prospectively maintained stroke database was reviewed for all patients presenting between January 2013 and December 2019 to a tertiary care academic comprehensive stroke center with acute, nontandem BAO. Patient data were extracted, subdivided by stroke mechanism and treatment modality (embolic [thrombectomy only] and intrinsic [thrombectomy + stenting]), and angiographic and clinical results were compared. Of 107 patients, 83 (78%) had embolic occlusions (thrombectomy only) and 24 (22%) had intrinsic disease (thrombectomy + stenting). There was no significant difference in patient age, presenting National Institutes of Health Stroke Scale score, time to presentation, selected medical comorbidities (hypertension, hyperlipidemia, diabetes, and atrial fibrillation), prior stroke, and posterior circulation Alberta Stroke Program Early CT Score. Patients with intrinsic disease were more likely to be active smokers (50% vs 26%, p = 0.04) and more likely to be male (88% vs 48%, p = 0.001). Successful recanalization, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b or 3, was achieved in 90% of patients and did not differ significantly between the embolic versus intrinsic groups (89% vs 92%, p > 0.99). A 90-day good outcome (modified Rankin Scale [mRS] score 0-2) was found in 37% of patients overall and did not differ significantly between the two groups (36% vs 41%, p = 0.41). Mortality was 40% overall and did not significantly differ between groups (41% vs 36%, p = 0.45). In the current study, demographic and clinical results for acute BAO showed that compared with intrinsic disease, thromboembolic disease is a more common mechanism of acute BAO, with 78% of patients undergoing thrombectomy alone. However, there was no significant difference in revascularization and outcome results between patients with embolic disease and those with intrinsic disease.

Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study.

Posttraumatic stress disorder (PTSD) often co-occurs with alcohol consumption (AC) and alcohol use disorder (AUD). However, it is unknown whether the same etiologic influences that underlie PTSD co-occurring with AUD are those that underlie PTSD and AC individually. This study used large-scale genome-wide association study (GWAS) data to test whether PTSD and drinks per week [DPW]/AUD are causally related to one another, and, if so, whether PTSD precedes DPW/AUD and/or vice versa. We used Mendelian Randomization methods to analyze European ancestry GWAS summary statistics from the Psychiatric Genomics Consortium (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and the Million Veteran Program (MVP; AUD). PTSD exerted a potentially causal effect on AUD (β=0.039, SE=0.014, p=0.005), but not on DPW (β=0.002, SE=0.003, p=0.414). Additionally, neither DPW (β=0.019, SE=0.041, p=0.637) nor AUD (β=8.87×10-4 , SE=0.001, p=0.441) exerted a causal effect on PTSD. These findings are consistent with the self-medication model, in which individuals misuse alcohol to cope with aversive trauma-related symptoms. These findings extend latent analysis and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups to prioritize for prevention efforts. Further, they provide a rationale for future preclinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.

Developmental Language Disorder and Psychopathology: Disentangling Shared Genetic and Environmental Influences

There is considerable variability in the extent to which young people with developmental language disorder (DLD) experience mental health difficulties. What drives these individual differences remains unclear. In the current article, data from the Twin Early Development Study were used to investigate the genetic and environmental influences on psychopathology in children and adolescents with DLD (n = 325) and those without DLD (n = 865). Trivariate models were fitted to investigate etiological influences on DLD and psychopathology, and bivariate heterogeneity and homogeneity models were fitted and compared to investigate quantitative differences in etiological influences on psychopathology between those with and without DLD. The genetic correlation between DLD and internalizing problems in childhood was significant, suggesting that their co-occurrence is due to common genetic influences. Similar, but nonsignificant effects were observed for externalizing problems. In addition, genetic influences on internalizing problems, but not externalizing problems, appeared to be higher in young people with DLD than those without DLD, suggesting that the presence of DLD may exacerbate genetic risk for internalizing problems. These findings indicate that genetic influences on internalizing problems may also confer susceptibility to DLD (or vice versa) and that DLD serves as an additional risk factor for those with a genetic predisposition for internalizing problems.

Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Background & AimsIn this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program.MethodsIndividual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models.ResultsAmong 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact.ConclusionCompared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment.Lay summaryIt has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis.RegistrationCHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.