Dysmobility Syndrome Independently Increases Fracture Risk in the Osteoporotic Fractures in Men (MrOS) Prospective Cohort Study.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 <7.26 kg/m2 , total body fat >30%, spine or hip T-score ≤ -2.5, grip strength <30 kg, gait speed <1.0 m/s, and one or more fall within 12 months. We examined whether baseline DS increased the risk of hip and major osteoporotic fractures (MOFs) over a median of 14 years (IQR, 9 to 15 years). Among 5834 men mean age 74 ± 6 years, 471 (8%) had DS and 635 (11%) experienced an MOF, including 274 (5%) hip fractures. Age (per SD increase) conferred an HR of 1.72 (95% CI, 1.59 to 1.86), DS conferred an HR of 3.45 (95% CI, 2.78 to 4.29) and FRAX calculated with BMD (per %) conferred an HR of 1.10 (95% CI, 1.08 to 1.11) for MOF. Prediction of MOF using the FRAX score provided a concordance value of 0.67 ± 0.012 (concordance values are mean ± SE). Concordance increased to 0.69 ± 0.012 by adding DS and to 0.70 ± 0.012 by adding DS and age to the multivariate model. Kaplan-Meier curves indicated that men with both DS and a FRAX risk above the National Osteoporosis Foundation (NOF) treatment thresholds had higher MOF (HR 6.23; 95% CI, 3.10 to 12.54) and hip (HR 7.73; 95% CI, 5.95 to 10.04) fracture risk than men with neither condition. We suggest further studies to determine the optimal criteria for DS, and to test DS as a predictor of falls and fractures, especially in women. © 2018 American Society for Bone and Mineral Research.

Risk for colorectal neoplasia in patients with inflammatory bowel disease and mucosa indefinite for dysplasia.

BACKGROUND: The management of colonic epithelial changes indefinite for dysplasia (IND) in patients with inflammatory bowel disease (IBD) remains controversial because of a paucity of published outcome data. METHODS: We analyzed data from 93 patients with IBD who were IND and 52 IBD patients without dysplasia (controls) from the Department of Anatomic Pathology database at the Cleveland Clinic from 1989 to 2004. Pathology reports, histologic slides, clinical features, and outcomes were reviewed. RESULTS: Twenty-two patients (23.7%) had surgical resections within 6 months of the IND assignment; of these, 6 had dysplasia (27.3%; 1 low-grade dysplasia and 5 high-grade dysplasia [HGD]). The remaining 71 patients received regular colonoscopy examinations for a mean period of 98.6 months; 18 patients developed dysplasia or carcinoma (25.2%; 10 low-grade dysplasia, 5 HGD, and 3 colorectal cancer). There was a mean interval of 53.9 months between an IND assignment and identification of dysplasia or carcinoma. Histology review of 59 cases revealed 3.2 cases per 100 person-years for neoplasia (low-grade dysplasia, HGD, or colorectal cancer) and 1.5 cases per 100 person-years for advanced neoplasia (HGD or colorectal cancer); these values were higher than those for controls (1.9 cases per 100 person-years for neoplasia and 0.7 cases per 100 person-years for advance neoplasia; P = 0.1 and P = 0.2, respectively, for IND versus controls). Patients aged more than 44 years when they were found to be IND were more likely than younger patients to develop neoplasia (hazard ratio, 6.7; P = 0.01). CONCLUSIONS: Patients with IBD and IND are at significant risk for colorectal dysplasia and cancer. These patients should be closely followed.

Reducing the risk of surgical site infections: does chlorhexidine gluconate provide a risk reduction benefit?

Chlorhexidine gluconate (CHG) has been available as a topical antiseptic for over 50 years, having broad clinical application throughout the health care environment. Evidence-based clinical studies have shown chlorhexidine gluconate to be a safe and effective perioperative skin-prepping agent. Renewed interest has emerged for use of the antiseptic bath/shower to reduce the microbial skin burden prior to hospital admission. Recent clinical studies have documented that multiple applications of 2% or 4% CHG using a standardized protocol results in high skin surface concentrations sufficient to inhibit/kill skin colonizing flora, including methicillin-resistant Staphylococcus aureus. A new focus for the use of CHG in surgical patients involves irrigation of the wound prior to closure with 0.05% CHG followed by saline rinse. Recent laboratory studies suggest that, following a 1-minute exposure, 0.05% CHG produces a >5-log reduction against selective health care-associated pathogens and reduces microbial adherence to the surface of implantable biomedical devices. General, orthopedic, cardiothoracic, and obstetrical surgical studies have documented the safety of selective CHG formulations in elective surgical procedures. The following discussion will address both the evidence-based literature and preliminary findings suggesting that CHG has a broad and safe range of applications when used as an adjunctive interventional strategy for reducing the risk of postoperative surgical site infections (SSI).

Whole-Genome Sequencing to Identify Mutants and Polymorphisms in Chlamydomonas reinhardtii.

Whole-genome sequencing (WGS) provides a new platform for the identification of mutations that produce a mutant phenotype. We used Illumina sequencing to identify the mutational profile of three Chlamydomonas reinhardtii mutant strains. The three strains have more than 38,000 changes from the reference genome. NG6 is aflagellate and maps to 269 kb with only one nonsynonymous change; the V(12)E mutation falls in the FLA8 gene. Evidence that NG6 is a fla8 allele comes from swimming revertants that are either true or pseudorevertants. NG30 is aflagellate and maps to 458 kb that has six nonsynonomous changes. Evidence that NG30 has a causative nonsense allele in IFT80 comes from rescue of the nonswimming phenotype with a fragment bearing only this gene. This gene has been implicated in Jeune asphyxiating thoracic dystrophy. Electron microscopy of ift80-1 (NG30) shows a novel basal body phenotype. A bar or cap is observed over the distal end of the transition zone, which may be an intermediate in preparing the basal body for flagellar assembly. In the acetate-requiring mutant ac17, we failed to find a nonsynonymous change in the 676 kb mapped region, which is incompletely assembled. In these strains, 43% of the changes occur on two of the 17 chromosomes. The excess on chromosome 6 surrounds the mating-type locus, which has numerous rearrangements and suppressed recombination, and the changes extend beyond the mating-type locus. Unexpectedly, chromosome 16 shows an unexplained excess of single nucleotide polymorphisms and indels. Overall, WGS in combination with limited mapping allows fast and accurate identification of point mutations in Chlamydomonas.

Alcohol consumption and risk of stroke: a meta-analysis.

CONTEXT: Observational studies suggest that heavy alcohol consumption may increase the risk of stroke while moderate consumption may decrease the risk. OBJECTIVE: To examine the association between alcohol consumption and relative risk of stroke. DATA SOURCES: Studies published in English-language journals were retrieved by searching MEDLINE (1966-April 2002) using Medical Subject Headings alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke; Dissertation Abstracts Online using the keywords stroke and alcohol; and bibliographies of retrieved articles. STUDY SELECTION: From 122 relevant retrieved reports, 35 observational studies (cohort or case control) in which total stroke, ischemic stroke, or hemorrhagic (intracerebral or total) stroke was an end point; the relative risk or relative odds and their variance (or data to calculate them) of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and abstainers served as the reference group. DATA EXTRACTION: Information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, and risk estimates was abstracted independently by 3 investigators using a standardized protocol. DATA SYNTHESIS: A random-effects model and meta-regression analysis were used to pool data from individual studies. Compared with abstainers, consumption of more than 60 g of alcohol per day was associated with an increased relative risk of total stroke, 1.64 (95% confidence interval [CI], 1.39-1.93); ischemic stroke, 1.69 (95% CI, 1.34-2.15); and hemorrhagic stroke, 2.18 (95% CI, 1.48-3.20), while consumption of less than 12 g/d was associated with a reduced relative risk of total stroke, 0.83 (95%, CI, 0.75-0.91) and ischemic stroke, 0.80 (95% CI, 0.67-0.96), and consumption of 12 to 24 g/d was associated with a reduced relative risk of ischemic stroke, 0.72 (95%, CI, 0.57-0.91). The meta-regression analysis revealed a significant nonlinear relationship between alcohol consumption and total and ischemic stroke and a linear relationship between alcohol consumption and hemorrhagic stroke. CONCLUSIONS: These results indicate that heavy alcohol consumption increases the relative risk of stroke while light or moderate alcohol consumption may be protective against total and ischemic stroke.