Objectives: To assess patients with different types of mutations of the β myosin heavy chain (β MHC) gene causing hypertrophic cardiomyopathy (HCM) and to determine the prognosis of patients according to the affected functional domain of β MHC. Design and setting: Cohort study of subjects referred to an HCM clinic at an academic hospital. Patients: 70 probands from the HCM clinic were screened for mutations of the β MHC gene and 148 family members of the genotype positive probands were further assessed. The control group for the genetic studies consisted of 106 healthy subjects. Main outcome measures: Direct DNA sequencing was used to screen 70 probands for mutations of the β MHC gene. Family members underwent genotypic and detailed clinical, ECG, and echocardiographic assessments. The survival of genotype positive subjects was evaluated according to the type of functional domain affected by the missense mutation and according to phenotypic characteristics. Results: A mutation of the β MHC gene was detected in 15 of 70 probands (21%). Of 148 family members studied in these 15 families, 74 were identified with a β MHC defect. Eleven mutations were detected, including four novel mutations: Ala196Thr, Pro211Leu, Val404Leu, and Arg870Cys. Median survival was 66 years (95% confidence interval (CI) 64 to 77 years) in all affected subjects. There was a significant difference in survival between subjects according to the affected functional domain (p = 0.02). Significant independent predictors of decreased survival were the non-conservative (that is, associated with a change in the amino acid charge) missense mutations that affected the actin binding site (hazard ratio 4.4, 95% CI 1.6 to 11.8; p = 0.003) and those that affected the rod portion of β MHC (hazard ratio 4.8, 95% CI 1.2 to 19.4; p = 0.03). No phenotypic characteristics were associated with decreased survival or cardiovascular morbidity. Conclusions: The type of β MHC functional domain affected by the missense mutation is predictive of overall prognosis in HCM.H ypertrophic cardiomyopathy (HCM) is a primary and clinically diverse cardiac disorder that is caused by a defect in one of 10 genes encoding proteins of the myofibrillar apparatus: β myosin heavy chain (β MHC), α myosin heavy chain, myosin binding protein C, troponin T, α tropomyosin, troponin I, myosin essential light chain 1, myosin regulatory light chain 2, α cardiac actin, or titin. [1][2][3] There is significant genetic heterogeneity in HCM with more than 150 mutations now implicated in its pathogenesis. The β MHC gene was the first gene identified with this condition.6 Defects of the β MHC gene account for the largest proportion of cases of HCM and many of the initial genotypephenotype correlative studies of HCM were based on subjects with defects of β MHC. Certain mutations have been associated with a significantly shorter life expectancy in patients with HCM. 4 7-10 However, the associations between specific genotypes and overall prognosis are based on findings from a limited number of familie...

Background: Obtaining intraoperative cultures of allograft bone just before use in ortho pedic procedures is standard practice in many centres; however, the association between positive cultures and subsequent surgical infections is unknown. Our study had 3 goals: to determine the prevalence of positive intraoperative allograft culture and subsequent infec tion; to determine if, in cases of subsequent infection, organisms isolated at reoperation were the same as those cultured from the allograft at the time of the index procedure; and to assess the costs associated with performing intraoperative allograft cultures. Methods:In this retrospective case series, we obtained data on patients receiving allograft bone between 2009 and 2012. Patients receiving allograft with positive cul tures were reviewed to identify cases of significant infection. Organisms isolated at reoperation were compared with the allograft culture taken at the time of implanta tion, and we performed a cost assessment.Results: Of the 996 allograft bone grafts used, 43 (4.3%) had positive intraoperative cultures and significant postoperative infections developed in 2, requiring reoperation. Antibiotics based on culture results were prescribed in 24% of cases. Organisms cul tured at the time of reoperation differed from those isolated initially. The cost of per forming 996 allograft cultures was $169 320. Conclusion:This series suggests that rates of positive intraoperative bone allograft culture are low, and subsequent infection is rare. In cases of postoperative infection, primary allograft culture and secondary tissue cultures isolated different organisms. Costs associated with performing cultures are high. Eliminating initial culture testing could save $42 500 per year in our health region.Contexte : L'obtention de cultures d'allogreffes osseuses peropératoires juste avant une intervention orthopédique est une pratique standard dans de nombreux centres. Or, on ignore s'il y a un lien entre des résultats de cultures positifs et les infections chirurgicales subséquentes. Notre étude avait 3 objectifs : déterminer la prévalence des cultures d'allogreffes peropératoires positives et des infections subséquentes; déterminer si, dans les cas d'infections subséquentes, les agents pathogènes isolés lors d'une réintervention étaient les mêmes que dans les spécimens prélevés sur les allogreffes au moment des interventions initiales; évaluer les coûts associés à l'obtention des cultures d'allogreffes peropératoires.

Introduction Necrotising fasciitis is a life-threatening rapidly progressing bacterial infection of the skin requiring prompt diagnosis and treatment. Optimum care warrants a combination of surgical debridement, antibiotics and intensive care support. All cases of necrotising fasciitis in 10 years in the North East of Scotland were reviewed to investigate and improve patient care. Methods Cases between August 2006 and February 2016 were reviewed using case notes and electronic hospital records. Data including mode of admission, clinical observations, investigations, operative interventions, microbiological and clinical outcomes was collected and reviewed. Analysis required multidisciplinary input including microbiology, infectious disease, trauma and orthopaedics, plastic surgery and intensive care teams. Results A total of 36 cases were identified. The mean laboratory risk indicator for necrotising fasciitis (LRINEC) score was 7 and 86% of patients fulfilled the criteria for necrotising fasciitis. Patients were commonly haemodynamically stable upon admission but deteriorated rapidly; 36% of patients had a temperature of over 37.5 degrees C on initial observations; 29/36 patients were discharged, 6 patients died acutely (acute mortality rate of 17%); 18/31 of cases were polymicrobial with Streptococcus pyogenes, the common organism. Six amputations or disarticulations were performed from a total of 82 operations in this group, with radical debridement the usual primary operation. The mean time to theatre was 3.54 hours. Highly elevated admission respiratory rate (50 breaths/minute) was associated with increased mortality. Conclusions Necrotising fasciitis presents subtly and carries significant morbidity and mortality. A high index of suspicion allows early diagnosis and intervention. We believe that a pan-specialty approach is the cornerstone for good outcomes.