Fulminant immune-mediated necrotising myopathy (IMNM) mimicking myocardial infarction with non-obstructive coronary arteries (MINOCA)

A 74-year-old man, with inflammatory arthritis, recently commenced on adalimumab, presented with a 4-week history of left-sided chest pain, malaise and shortness of breath. Admission ECG showed age-indeterminate left bundle branch block. Troponin T was 4444 ng/L (normal range <15 ng/L) and acute coronary syndrome treatment was commenced. Catheter angiogram revealed mild-burden non-obstructive coronary disease. Cardiac magnetic resonance (CMR) was performed to refine the differential diagnosis and demonstrated no myocardial oedema or late gadolinium enhancement. Extracardiac review highlighted oedema and enhancement of the left shoulder girdle muscles consistent with acute myositis. Creatine kinase was subsequently measured and significantly elevated at 7386 IU/L (normal range 30–200 IU/L in men). Electrophoresis clarified that this was of predominantly skeletal muscle origin. Myositis protocol MRI revealed florid skeletal muscle oedema. The MR findings, together with positive anti-Scl-70 antibodies, suggested fulminant immune-mediated necrotising myopathy presenting as a rare mimic of myocardial infarction with non-obstructive coronary arteries, diagnosed by careful extracardiac CMR review

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead