Surgeon choice in the use of postdischarge antibiotics for prophylaxis following mastectomy with and without breast reconstruction

Multiple guidelines recommend discontinuation of prophylactic antibiotics \u3c24 hours after surgery. In a multicenter, retrospective cohort of 2,954 mastectomy patients ± immediate breast reconstruction, we found that utilization of prophylactic postdischarge antibiotics varied dramatically at the surgeon level among general surgeons and was virtually universal among plastic surgeons

Postdischarge antibiotic use for prophylaxis following spinal fusion

OBJECTIVE: Despite recommendations to discontinue prophylactic antibiotics after incision closure or \u3c24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion. DESIGN: Multicenter retrospective cohort study. PATIENTS: This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded. METHODS: Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models. RESULTS: In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). Adjusted for study site, significant factors associated with prophylactic discharge antibiotics included American Society of Anesthesiologists (ASA) class ≥3 (odds ratio [OR], 1.31; 95% CI, 1.00-1.70), lymphoma (OR, 2.57; 95% CI, 1.11-5.98), solid tumor (OR, 3.63; 95% CI, 1.62-8.14), morbid obesity (OR, 1.64; 95% CI, 1.09-2.47), paralysis (OR, 2.38; 95% CI, 1.30-4.37), hematoma/seroma (OR, 2.93; 95% CI, 1.17-7.33), thoracic surgery (OR, 1.39; 95% CI, 1.01-1.93), longer length of stay, and intraoperative antibiotics. CONCLUSIONS: Postdischarge prophylactic antibiotics were uncommon after spinal fusion. Patient and perioperative factors were associated with continuation of prophylactic antibiotics after hospital discharge

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Seawater carbonate chemistry and micromechanical properties of the mineralized cuticle in juvenile red and blue king crabs

Ocean acidification (OA) adversely affects a broad range of marine calcifying organisms. Crustaceans, however, exhibit mixed responses to OA, with growth or survival negatively affected in some species, but unaffected or positively affected in others. In crustaceans, the mineralized cuticle resists mechanical loads, provides protection from the environment, and enables mobility, but little is known about how OA or interactions between OA and temperature affect its structure or function. Here, the effects of OA on the mechanics, structure, and composition of the cuticle in two Alaska king crab species was assessed. Juvenile blue king crabs (Paralithodes platypus) were exposed for a year to three pH levels, 8.1 (ambient), 7.8 and 7.5. Juvenile red king crabs (Paralithodes camtschaticus) were exposed for ~ 6 months to two pH levels, 8.0 and 7.8, at three temperatures: ambient, ambient + 2 °C, and ambient + 4 °C. Cuticle microhardness (a measure of resistance to permanent or plastic mechanical deformation), thickness, ultrastructure, and elemental composition were assessed in two body regions, the carapace and the crushing chela (claw). In both species tested, OA reduced endocuticle microhardness in the chela, but not in the carapace. There was no effect of pH or temperature on total procuticle thickness of the chela or carapace in either species. Reductions in microhardness were not driven by reduced calcium content of the shell. In fact, calcium content was significantly elevated in the carapace of blue king crabs and in the chela of red king crabs exposed to lower than ambient pH at ambient temperature, suggesting that calcium content alone is not a sufficient proxy for mechanical properties. Reduced chela microhardness, indicative of more compliant material, could compromise the utility of crushing chelae in feeding and defense