Risk factors for persistent postoperative opioid use: an entity distinct from chronic postsurgical pain.

Despite a decline in opioid prescriptions over the past decade, patients commonly receive opioid analgesics as a treatment for postoperative pain in the USA. One complication that patients may experience after surgery is persistent postoperative opioid use (PPOU), or opioid use beyond the typical recovery period. Often defined as beyond 3 months postsurgery, PPOU is frequently conflated with chronic postsurgical pain (CPSP), where pain persists well after the expected healing time following surgery.

The Association of Preoperative Opioid Use with Post-Discharge Outcomes: A Cohort Study of the Michigan Surgical Quality Collaborative.

Objective: To examine the association of prescription opioid fills over the year prior to surgery with postoperative outcomes.

Background: Nearly one third of patients report opioid use in the year preceding surgery, yet an understanding of how opioid exposure influences patient-reported outcomes after surgery remains incomplete. Therefore, this study was designed to test the hypothesis that preoperative opioid exposure may impede recovery in the postoperative period.

Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-analyses.

Background: Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation.

Clinical consequences of a polygenic predisposition to benign lower white blood cell counts: Consequences of benign WBC count genetics.

Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGS) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio=0.

The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction.

Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critical to cardiac function. Mice lacking an ortholog of sandman, TWIK-related potassium channel (TREK-1, also known Kcnk2), exhibit exaggerated pressure overload-induced concentric hypertrophy and alterations in fetal gene expression, yet retain preserved systolic and diastolic cardiac function.

Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a defining ciliopathy, notable for extensive allelic and genetic heterogeneity, almost all of which has been identified through sequencing. Recent data have suggested that copy-number variants (CNVs) also contribute to BBS. We used a custom oligonucleotide array comparative genomic hybridization (aCGH) covering 20 genes that encode intraflagellar transport (IFT) components and 74 ciliopathy loci to screen 92 unrelated individuals with BBS, irrespective of their known mutational burden.

Identification of cis-suppression of human disease mutations by comparative genomics.

Patterns of amino acid conservation have served as a tool for understanding protein evolution. The same principles have also found broad application in human genomics, driven by the need to interpret the pathogenic potential of variants in patients. Here we performed a systematic comparative genomics analysis of human disease-causing missense variants.

Interpreting human genetic variation with in vivo zebrafish assays.

Rapid advances and cost erosion in exome and genome analysis of patients with both rare and common genetic disorders have accelerated gene discovery and illuminated fundamental biological mechanisms. The thrill of discovery has been accompanied, however, with the sobering appreciation that human genomes are burdened with a large number of rare and ultra rare variants, thereby posing a significant challenge in dissecting both the effect of such alleles on protein function and also the biological relevance of these events to patient pathology. In an effort to develop model systems that are able to generate surrogates of human pathologies, a powerful suite of tools have been developed in zebrafish, taking advantage of the relatively small (compared to invertebrate models) evolutionary distance of that genome to humans, the orthology of several organs and signaling processes, and the suitability of this organism for medium and high throughput phenotypic screening.

Cardiomyopathy is associated with ribosomal protein gene haplo-insufficiency in Drosophila melanogaster.

The Minute syndrome in Drosophila melanogaster is characterized by delayed development, poor fertility, and short slender bristles. Many Minute loci correspond to disruptions of genes for cytoplasmic ribosomal proteins, and therefore the phenotype has been attributed to alterations in translational processes. Although protein translation is crucial for all cells in an organism, it is unclear why Minute mutations cause effects in specific tissues.