Accuracy of the diagnosis of malignant hyperthermia in hospital discharge records

Background: In 1997, the International Classification of Diseases, 9th Revision Clinical Modification (ICD-9CM) coding system introduced the code for malignant hyperthermia (MH) (995.86). The aim of the current study was to estimate the accuracy of coding for MH in hospital discharge records. Materials and methods: A panel of anesthesiologists expert in MH, reviewed medical records for patients with a discharge diagnosis of MH based on ICD-9 or ICD-10 codes from January 1, 2006 to December 31, 2008 at six tertiary care medical centers in North America. All cases were categorized as possible, probable, or fulminant MH, history of MH (family or personal) or other. Results: A total of 47 medical records were identified and reviewed by three experts. The mean age of patients was 40 years and 49% were male. A surgical procedure with general anesthesia was documented in 68% of patients. However, only 23.4% were judged to have had a possible, probable, or fulminant MH event. Dantrolene was given in 81% of MH cases. Family and personal history of MH accounted for 46.8% of cases. High fever without evidence of MH during admission accounted for 23.4%, and in 6.4% cases the reason for the code was not apparent. All patients judged to have an incident MH event survived to discharge. Conclusions: Medical record coding for MH typically includes both incident cases as well as a history of MH. The positive predictive value of about 70% for MH in this study are consistent with other studies of ICD-9 accuracy in the US. However, epidemiologic studies based on coded diagnosis of MH should carefully distinguish between incident cases related to anesthesia, cases unrelated to anesthesia and diagnosis based on history only

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways

Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine

Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

The association between child maltreatment and emotional, cognitive, and physical health functioning in Vietnam

Abstract Background There is a paucity of research on correlates of child maltreatment in limited-resource countries with a relatively high tolerance of harsh discipline. This Vietnamese study aimed to investigate associations between different types of child maltreatment and child emotional, cognitive, and physical health functioning as well as moderation effects of gender and ethnicity. Methods This cross-sectional study was conducted with 1851 randomly selected students aged 12–17 years. Both self-report and more objective measures (weight, height, study ranking, and a memory test) were used. Results All types of child maltreatment were associated with emotional dysfunctioning. Life time and past year experiences of physical abuse and life time experiences of sexual abuse and neglect were related to poorer perceived physical health. The study did not find associations between any type of child maltreatment and overweight or underweight status. Regarding cognitive functioning, life time experience of sexual abuse and neglect were related to poorer working memory performance. Noticeably, emotional abuse was related to better academic performance, which might be an indication of “tiger parenting” practice in Vietnam, implying academic performance stimulation at the expense of emotional security. No significant moderation effects by gender and ethnicity were found. Conclusion Even in a culture in which harsh discipline is normative, child maltreatment was related to negative aspects of child wellbeing including emotional, cognitive, and physical health functioning. Efficient and low-cost interventions on child maltreatment should be developed and conducted in Vietnam as well as other countries with similar contexts

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts