Alexandra B. Columbus

Autosomal recessive inheritance of classic Bethlem myopathy.

Mutations in the collagen VI genes (COL6A1, COL6A2 and COL6A3) result in Ullrich congenital muscular dystrophy (CMD), Bethlem myopathy or phenotypes intermediate between Ullrich CMD and Bethlem myopathy. While Ullrich CMD can be caused by either recessively or dominantly acting mutations, Bethlem myopathy has thus far been described as an exclusively autosomal dominant condition. We report two adult siblings with classic Bethlem myopathy who are compound heterozygous for a single nucleotide deletion (exon 23; c.1770delG), leading to in-frame skipping of exon 23 on the maternal allele, and a missense mutation p.R830W in exon 28 on the paternal allele. The parents are carriers of the respective mutations and are clinically unaffected. The exon skipping mutation in exon 23 results in a chain incapable of heterotrimeric assembly, while p.R830W likely ameliorates the phenotype into the Bethlem range. Thus, autosomal recessive inheritance can also underlie Bethlem myopathy, supporting the notion that Ullrich CMD and Bethlem myopathy are part of a common clinical and genetic spectrum.

Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1.

OBJECTIVE Reducing body myopathy (RBM) is a rare progressive disorder of muscle characterized by intracytoplasmic inclusions, which stain strongly with menadione-NBT (nitroblue tetrazolium). We recently identified the four and a half LIM domain gene FHL1 located on chromosome Xq26 as the causative gene for RBM. So far eight familial cases and 21 sporadic patients with RBM have been reported in the literature. METHODS We ascertained a total of 8 members of a German family initially reported by Goebel et al. as a mixed myopathy with rigid spine myopathy and reducing as well as cytoplasmic bodies. Clinical findings in the original and additional family members have been reviewed. Mutation detection was performed by direct sequencing of FHL1 exons. RESULTS We identified a novel mutation (p.C150R) in the second LIM domain of FHL1 in six family members (1 male, 5 females). The male index patient was the most affected member presenting with rigid spine, followed by rapidly progressive muscle weakness. He died from the consequences of respiratory insufficiency at the age of 29.5 years. His sister, mother, grandmother, aunt and female cousin all carried the mutation in the heterozygous state. The sister is clinically unaffected; their mother had myopathic changes in her muscle biopsy, while the grandmother showed first signs of weakness at 50 years of age. The 54-year-old aunt and her daughter are clinically asymptomatic. CONCLUSION We report a novel LIM2 domain mutation in FHL1 in a previously reported family with RBM with cytoplasmic bodies and spinal rigidity. While the male index patient was significantly affected, female carriers show varying manifestations and may be asymptomatic, likely reflecting varying degrees of X-inactivation. RBM continues to be associated with mutations in the LIM2 domain of FHL1. We also confirm our earlier observation that mutations at the N-terminal end of the LIM2 domain seem to be milder compared to mutations seen at the C-terminal part of the domain which cause severe disease even in female carriers.

Malnutrition at Intensive Care Unit Admission Predicts Mortality in Emergency General Surgery Patients.

BACKGROUND Emergency general surgery (EGS) patients are at an increased risk for morbidity and mortality compared with non-EGS patients. Limited information exists regarding the contribution of malnutrition to the outcome of critically ill patients who undergo EGS. We hypothesized that malnutrition would be associated with increased risk of 90-day all-cause mortality following intensive care unit (ICU) admission in EGS patients. MATERIALS AND METHODS We performed an observational study of patients treated in medical and surgical ICUs at a single institution in Boston. We included patients who underwent an EGS procedure and received critical care between 2005 and 2011. The exposure of interest, malnutrition, was determined by a registered dietitians formal assessment within 48 hours of ICU admission. The primary outcome was all-cause 90-day mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS The cohort consisted of 1361 patients. Sixty percent had nonspecific malnutrition, 8% had protein-energy malnutrition, and 32% were without malnutrition. The 30-day readmission rate was 18.9%. Mortality in-hospital and at 90 days was 10.1% and 17.9%, respectively. Patients with nonspecific malnutrition had a 1.5-fold increased odds of 90-day mortality (adjusted odds ratio [OR], 1.51; 95% confidence interval [CI], 1.09-5.04; P = .009) and patients with protein-energy malnutrition had a 3.1-fold increased odds of 90-day mortality (adjusted OR, 3.06; 95% CI, 1.89-4.92; P < .001) compared with patients without malnutrition. CONCLUSION In critically ill patients who undergo EGS, malnutrition at ICU admission is predictive of adverse outcomes. In survivors of hospitalization, malnutrition at ICU admission is associated with increases in readmission and mortality.

Association of Model for End-Stage Liver Disease Score With Mortality in Emergency General Surgery Patients

IMPORTANCE Emergency general surgery (EGS) patients have a disproportionate burden of death and complications. Chronic liver disease (CLD) increases the risk of complications following elective surgery. For EGS patients with CLD, long-term outcomes are unknown and risk stratification models do not reflect severity of CLD. OBJECTIVE To determine whether the Model for End-Stage Liver Disease (MELD) score is associated with increased risk of 90-day mortality following intensive care unit (ICU) admission in EGS patients. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study of patients with CLD who underwent an EGS procedure based on International Classification of Diseases, Ninth Revision (ICD-9) procedure codes and were admitted to a medical or surgical ICU within 48 hours of surgery between January 1, 1998, and September 20, 2012, at 2 academic medical centers. Chronic liver disease was identified using ICD-9 codes. Multivariable logistic regression was performed. The analysis was conducted from July 1, 2015, to January 1, 2016. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause 90-day mortality. RESULTS A total of 13 552 EGS patients received critical care; of these, 707 (5%) (mean [SD] age at hospital admission, 56.6 [14.2] years; 64% male; 79% white) had CLD and data to determine MELD score at ICU admission. The median MELD score was 14 (interquartile range, 10-20). Overall 90-day mortality was 30.1%. The adjusted odds ratio of 90-day mortality for each 10-point increase in MELD score was 1.63 (95% CI, 1.34-1.98). A decrease in MELD score of more than 3 in the 48 hours following ICU admission was associated with a 2.2-fold decrease in 90-day mortality (odds ratio = 0.46; 95% CI, 0.22-0.98). CONCLUSIONS AND RELEVANCE In this study, MELD score was associated with 90-day mortality following EGS in patients with CLD. The MELD score can be used as a prognostic factor in this patient population and should be used in preoperative risk prediction models and when counseling EGS patients on the risks and benefits of operative intervention.

Hospital Factors Associated With Care Discontinuity Following Emergency General Surgery

Importance Although there is evidence that changes in clinicians during the continuum of care (care discontinuity) are associated with higher mortality and complications among surgical patients, little is known regarding the drivers of care discontinuity among emergency general surgery (EGS) patients. Objective To identify hospital factors associated with care discontinuity among EGS patients. Design, Setting, and Participants We performed a retrospective analysis of the 100% Medicare inpatient claims file, from January 1, 2008, to November 30, 2011, and matched patient details to hospital information in the 2011 American Hospital Association Annual Survey database. We selected patients aged 65 years and older who had the most common procedures associated with the previously defined American Association for the Surgery of Trauma EGS diagnosis categories and survived to hospital discharge across the United States. The current analysis was conducted from February 1, 2016, to March 24, 2016. Main Outcomes and Measures Care discontinuity defined as readmission within 30 days to nonindex hospitals. Results There were 109 443 EGS patients readmitted within 30 days of discharge and 20 396 (18.6%) were readmitted to nonindex hospitals. Of the readmitted patients, 61 340 (56%) were female. Care discontinuity was higher among patients who were male (19.5% vs 18.0%), those younger than 85 years old (19.0% vs 16.6%), and those who lived 12.8 km (8 miles) or more away from the index hospitals (23.7% vs 14.8%) (all P < .001). Care discontinuity was independently associated with mortality (adjusted odds ratio [aOR], 1.16; 95% CI, 1.08-1.25). Hospital factors associated with care discontinuity included bed size of 200 or more (aOR, 1.45; 95% CI, 1.36-1.54), safety-net status (aOR, 1.35; 95% CI, 1.27-1.43), and teaching status (aOR, 1.18; 95% CI, 1.09-1.28). Care discontinuity was significantly lower among designated trauma centers (aOR, 0.89; 95% CI, 0.83-0.94) and highest among hospitals in the Midwest (aOR, 1.15; 95% CI, 1.05-1.26). Conclusions and Relevance Nearly 1 in 5 older EGS patients is readmitted to a hospital other than where their original procedure was performed. This care discontinuity is independently associated with mortality and is highest among EGS patients who are treated at large, teaching, safety-net hospitals. These data underscore the need for sustained efforts in increasing continuity of care among these hospitals and highlight the importance of accounting for these factors in risk-adjusted hospital comparisons.

Risk stratification tools in emergency general surgery

The use of risk stratification tools (RST) aids in clinical triage, decision making and quality assessment in a wide variety of medical fields. Although emergency general surgery (EGS) is characterized by a comorbid, physiologically acute patient population with disparately high rates of perioperative morbidity and mortality, few RST have been explicitly examined in this setting. We examined the available RST with the intent of identifying a tool that comprehensively reflects an EGS patients perioperative risk for death or complication. The ideal tool would combine individualized assessment with relative ease of use. Trauma Scoring Systems, Critical Care Scoring Systems, Surgical Scoring Systems and Track and Trigger Models are reviewed here, with the conclusion that Emergency Surgery Acuity Score and the American College of Surgeons National Surgical Quality Improvement Programme Universal Surgical Risk Calculator are the most applicable and appropriate for EGS.

An evidence-based intraoperative communication tool for emergency general surgery: a pilot study

BACKGROUND Emergency general surgery (EGS) is characterized by high rates of morbidity and mortality. Though checklists and associated communication-based huddle strategies have improved outcomes, these tools have never been specifically examined in EGS. We hypothesized that use of an evidence-based communication tool aimed to trigger intraoperative discussion could improve communication in the EGS operating room (OR). MATERIALS AND METHODS We designed a set of discussion prompts based on modifiable factors identified from previously published studies aimed to encourage all team members to speak up and to centralize awareness of patient disposition and intraoperative transfusion practices. This tool was pilot-tested using OR human patient simulators and was then rolled out to EGS ORs at an academic medical center. The perceived effect of our tools implementation was evaluated through mixed-methodologic presurvey and postsurvey analysis. RESULTS Preimplementation and postimplementation survey-based data revealed that providers reported the EGS-focused discussion prompts as improving team communication in EGS. A trend toward shared awareness of intraoperative events was observed; however, nurses described cultural impedance of discussion initiation. Providers described a need for further reinforcement of the tool and its indications during implementation. CONCLUSIONS Use of a discussion-based communication tool is perceived as supporting team communication in the EGS OR and led to a trend toward improving a shared understanding of intraoperative events. Analyses suggest the need for enhanced reinforcement of use during implementation and improvement of team-based education regarding EGS. Furthermore work is needed to understand the full impact of this evidence-based tool on OR team dynamics and EGS patient outcomes.