Bone defects following curettage do not necessarily need augmentation: A retrospective study of 146 patients

Background and purpose The natural pattern of bone healing in large bony defects following curettage alone as treatment of benign bone tumors around the knee is not well reported. We analyzed the outcome in 146 patients

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe

Indicaciones, técnicas y resultados de reemplazo total de cadera en estados unidos

Hace 50 años, Sir John Charnley introdujo la era del reemplazo total de cadera. Sus innovaciones en la fijación de la prótesis con polimetilmetacrilato, el par de fricción de metal/ polietileno, la instrumentación estandarizada y los quirófanos con aire purificado, revolucionaron los intentos previos a reemplazar caderas con artrosis. En Estados Unidos, los principios y la prótesis de Charnley fueron adoptados, investigados y modificados tal como lo ha sido en otros países. Sin embargo, su técnica y conceptos básicos siguen estando vigentes y el reemplazo total de cadera es ampliamente considerado uno de los procedimientos quirúrgicos más exitosos en la cirugía ortopédica. Más de 400.000 reemplazos de cadera son realizados anualmente en los Estados Unidos

Indications, techniques and results of total hip replacement in the united states

Sir John Charnley ushered in the era of total hip replacement over 50 years ago. His innovations of polymethylmethacrylate fixation of implants, polyethylene/metal bearing surfaces, standardized instrumentation, and clean air operating rooms revolutionized previous attempts to replace arthritic hips. In the United States, Charnley's principles and implants were adopted, investigated, and modified as they have been in most countries. His basic concepts and techniques remain valid, however, and total hip replacement is widely regarded as one of the most successful procedures in orthopaedic surgery. Over 400,000 hip replacements are now performed annually in the United States

Optimized Risk Score to Predict Mortality in Patients With Cardiogenic Shock in the Cardiac Intensive Care Unit

Background Mortality prediction in critically ill patients with cardiogenic shock can guide triage and selection of potentially high‐risk treatment options. Methods and Results We developed and externally validated a checklist risk score to predict in‐hospital mortality among adults admitted to the cardiac intensive care unit with Society for Cardiovascular Angiography & Interventions Shock Stage C or greater cardiogenic shock using 2 real‐world data sets and Risk‐Calibrated Super‐sparse Linear Integer Modeling (RiskSLIM). We compared this model to those developed using conventional penalized logistic regression and published cardiogenic shock and intensive care unit mortality prediction models. There were 8815 patients in our training cohort (in‐hospital mortality 13.4%) and 2237 patients in our validation cohort (in‐hospital mortality 22.8%), and there were 39 candidate predictor variables. The final risk score (termed BOS,MA2) included maximum blood urea nitrogen ≥25 mg/dL, minimum oxygen saturation <88%, minimum systolic blood pressure <80 mm Hg, use of mechanical ventilation, age ≥60 years, and maximum anion gap ≥14 mmol/L, based on values recorded during the first 24 hours of intensive care unit stay. Predicted in‐hospital mortality ranged from 0.5% for a score of 0 to 70.2% for a score of 6. The area under the receiver operating curve was 0.83 (0.82–0.84) in training and 0.76 (0.73–0.78) in validation, and the expected calibration error was 0.9% in training and 2.6% in validation. Conclusions Developed using a novel machine learning method and the largest cardiogenic shock cohorts among published models, BOS,MA2 is a simple, clinically interpretable risk score that has improved performance compared with existing cardiogenic‐shock risk scores and better calibration than general intensive care unit risk scores

Comparação entre os bioenxertos de hidroxiapatita de cálcio e submucosa de intestino delgado porcino no preenchimento de defeitos ósseos criados em mandíbula de ratos Defect repair in rat mandible with hydroxyapatite cement comparad to small intestine submucosa

OBJETIVO: O objetivo do presente estudo consiste em avaliar a regeneração óssea em defeito criado na mandíbula de ratos utilizando dois bioenxertos: hidroxiapatita de cálcio sintética e submucosa de intestino delgado porcina. FORMA DE ESTUDO: Experimental randomizado. MATERIAL E MÉTODO: Foram utilizados 24 ratos da linhagem Wisthar-Furth. Um defeito ósseo de 0,75cm x 1,5cm no corpo de cada hemimandíbula foi realizado em todos os animais com broca esférica de baixa rotação. Padronizou-se à esquerda o preenchimento do defeito ósseo, no grupo I com 15 microgramas de hidroxiapatita e no grupo II com preenchimento de submucosa de intestino delgado porcina (SID), e à direita o não-preenchimento serviu como controle. A eutanásia foi realizada no 40° dia de pós-operatório, após a qual se procederam as análises macroscópicas e histológicas das peças. RESULTADOS: O comprimento médio em milímetros das hemimandíbulas do grupo hidroxiapatita foi de 3,75, e o do grupo SID 3,03 e o do grupo controle foi de 2,63 (p: 0,0022). No grupo hidroxiapatita a neoformação óssea perfez uma área correspondente à 76,64% do total já no grupo SID 63,64% do total. CONCLUSÃO: Os resultados macroscópios e microscópicos foram superiores com a utilização do enxerto de hidroxiapatita quando comparado ao grupo submucosa de intestino delgado porcino. Entretanto os dois bioenxertos mostraram-se osteoindutores quando comparados ao controle.<br>AIM: The aim of this study was to evaluate the bone formation in surgically created defects of rabbit mandibles by synthetic hydroxyapatite of calcium compared to small Intestine Submucosa. MATERIAL AND METHOD: 24 mices lineage Wisthar-Furth were used. A bony defect of 0,75 cm x 1,5 cm in mandibular ramus was accomplished in all animals. The hydroxyapatite implants were placed on the left hemimandiblein groupI, small Intestine submucosa in group II, and the right served as control. The euthanasia was accomplished in the 40° postoperative day, it was proceeded the macroscopic and histological analysis. RESULTS: medium length in millimeters of the hemimandibless in the hydroxyapatite group was of 3,75, in the small intestine submucosa 3,03 and the control group was of 2,63 (p: 0,022). Histomorphometry study reaveled new bone grown in 76,64% of the total area in hydroxyapatite group (p: 0,022). In Small Intestinal submucosa group new bone grown in 63,64% do total (p: 0,0022). DISCUSSION: satisfactory bone integration was observed of the synthetic hydroxyapatite in that experimental model. Small intestinal submucosa cause osteoinduction CONCLUSÃO: using hydroxyapatite of calcium resulted in formation of significantly larger volume frations of new bone when compared to small intestinal submucosa group