Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

The Utility of Additional Imaging in Trauma Consults with Mild to Moderate Injury.

Limiting CT imaging in the ED has gained interest recently. After initial trauma workup for consultations in the ED, additional CT imaging is frequently ordered. We assessed the benefits of this additional imaging. Our hypothesis was that additional imaging in lower acuity trauma consults results in the diagnosis of new significant injuries with a change in treatment plan and increased Injury Severity Score (ISS). The registry at our Level I trauma center was queried from November 2015 to November 2016 for trauma consults initially evaluated by ED physicians. Patients with mild to moderate injuries were included. Injury findings before and after additional imaging were determined by chart review and pre- and postimaging ISS were calculated. Blinded trauma surgeons assessed the findings for clinical significance and changes in treatment. Four hundred and twenty-one patients were evaluated, 41 were excluded. One hundred and forty patients (37%) underwent additional CT imaging. Forty-seven patients (34%) had additional injuries found, with 16 (12%) increasing their ISS (mean 0.54, SD 1.66). Ninety-three per cent of cases resulted in at least one physician finding the new injuries clinically significant; however, agreement was low (κ = 0.095). For 70 per cent, at least one physician felt the findings warranted a change in treatment plan (κ = 0.405). Additional imaging in ED trauma consults resulted in the identification of new injuries in 1/3 of our patient sample. This suggests that current efforts to limit the use of CT imaging in trauma patients may result in significant injuries going undiscovered and undertreated. Further research is needed to determine the risk of attempts to limit imaging.

Parathyroid hormone as a marker for hypoperfusion in trauma: A prospective observational study.

BACKGROUND: Hyperparathyroidism is common in critical illness. Intact parathyroid hormone has a half-life of 3 minutes to 5 minutes due to rapid clearance by the liver, kidneys, and bone. In hemorrhagic shock, decreased clearance may occur, thus making parathyroid hormone a potential early marker for hypoperfusion. We hypothesized that early hyperparathyroidism predicts mortality and transfusion in trauma patients. METHODS: A prospective observational study was performed at a Level I trauma center in consecutive adult patients receiving the highest level of trauma team activation. Parathyroid hormone and lactic acid were added to the standard laboratory panel drawn in the trauma bay on arrival, before the administration of any blood products. The primary outcomes assessed were transfusion in 24 hours and mortality. RESULTS: Forty-six patients were included. Median age was 47 years, 82.6% were men, 15.2% suffered penetrating trauma, and 21.7% died. Patients who were transfused in the first 24 hours (n = 17) had higher parathyroid hormone (182.0 pg/mL vs. 73.5 pg/mL, p < 0.001) and lactic acid (4.6 pg/mL vs. 2.3 pg/mL, p = 0.001). Patients who did not survive to discharge (n = 10) also had higher parathyroid hormone (180.3 pg/mL vs. 79.3 pg/mL, p < 0.001) and lactic acid (5.5 mmol/L vs. 2.5 mmol/L, p = 0.001). For predicting transfusion in the first 24 hours, parathyroid hormone has an area under the receiver operating characteristic curve of 0.876 compared with 0.793 for lactic acid and 0.734 for systolic blood pressure. Parathyroid hormone has an area under the receiver operating characteristic curve of 0.875 for predicting mortality compared with 0.835 for lactic acid and 0.732 for systolic blood pressure. CONCLUSION: Hyperparathyroidism on hospital arrival in trauma patients predicts mortality and transfusion in the first 24 hours. Further research should investigate the value of parathyroid hormone as an endpoint for resuscitation. LEVEL OF EVIDENCE: Prognostic, level II.

Organ donation as an outcome of traumatic cardiopulmonary arrest: A cost evaluation.

BACKGROUND: Survival after traumatic cardiopulmonary arrest (TCPA) is rare and requires significant resource expenditure. Organ donation as an outcome of TCPA resuscitation has not yet been included in a cost analysis. The aims of this study were to identify variables associated with survival and organ donation after TCPA, and to estimate the cost of achieving these outcomes. We hypothesized that the inclusion of organ donation as a potential outcome would make TCPA resuscitation more cost-effective. METHODS: Adult patients who required resuscitation for TCPA at a level I trauma center were retrospectively reviewed over 36 months. Data were obtained from medical records, hospital accounting records, and the local organ procurement agency. Outcomes included survival to discharge, neurologic function, and organ donor eligibility. An individual-level state-transition cost-effectiveness model was used to evaluate the cost of TCPA resuscitation with and without organ donation included as an outcome. Incremental cost-effectiveness ratio was calculated to determine additional cost per life saved when organ donation is included. RESULTS: Over the study period, 8,932 subjects were evaluated. Traumatic cardiopulmonary arrest occurred in 237 patients (3%). The mortality rate was 97%. Variables associated with survival included emergency department disposition to the operating room (p < 0.01) and reactive pupils (p < 0.001). Of seven survivors, four were discharged neurologically intact. Of the patients with TCPA, 5% were eligible for organ donation with a procurement rate of 2%. Organ donor eligibility was associated with arrest after arrival to the emergency department (p < 0.01) and transfusion of fresh frozen plasma (p = 0.01). The cost of TCPA resuscitation per survivor was $1.8 million; cost per survivor or life saved by donation was $538,000. The incremental cost-effectiveness ratio was $76,816 per additional life saved including donation as an outcome. CONCLUSION: The decision to pursue resuscitation should continue to be based on the presence of signs of life, especially pupil reactivity and duration of arrest. If the primary objective is survival, organ procurement will be maximized without conflict of interest. Early fresh frozen plasma transfusion may increase successful organ donation. The financial burden of TCPA resuscitation can be mitigated by expanding end points to include organ donation. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III; cost analysis, level V.

A natural immune modulator attenuates stress hormone and catecholamine concentrations in polymicrobial peritonitis.

BACKGROUND: Activated hexose correlated compound (AHCC), derived from shiitake mushrooms, increases resistance to infection in immunocompromised hosts with positive effects on dendritic cells, natural killer cell function and interleukin 12 production. It may also be attenuating the systemic inflammatory response by regulating the secretion of cortisol and norepinephrine (NE). METHODS: Female Swiss-Weber mice were pretreated with AHCC (Amino Up Chemical Co., Sapporo, Japan) or water by gavage for 10 days before undergoing cecal ligation and puncture (CLP). Peritoneal exudate cells and blood samples were harvested at 4 hours and 24 hours following CLP. Plasma and peritoneal concentrations of cortisol and NE were obtained using enzyme-linked immunosorbent assay. Peritoneal bacteria were quantified by colony counts after 4 hours and 24 hours. Significance was denoted by a p < 0.05. RESULTS: Plasma and peritoneal cortisol concentrations were increased 4 hours after CLP compared with normal controls, with no difference between the pretreated groups. Concentrations of cortisol decreased from 4 hours to 24 hours after CLP with AHCC (plasma, p = 0.009; peritoneal, p < 0.001), and peritoneal cortisol at 24 hours was lower with AHCC as compared with water (p = 0.028). There was no change in plasma or peritoneal NE concentrations at 4 hours. At 24 hours, higher concentrations of NE were detected in both plasma and peritoneal fluid, with lower plasma concentrations in those gavaged with AHCC (p = 0.015). There was no significant difference in peritoneal bacteria counts. CONCLUSION: Enhanced immune function observed with AHCC could be caused by attenuated concentrations of stress hormones and catecholamines.

Bouveret syndrome: gallstone ileus of the duodenum.

This is a case of a 59-year-old woman with Bouveret syndrome. An initial endoscopic approach to management is described. Gallstone ileus occurs when a gallstone passes from a cholecystoduodenal fistula or a choledochoduodenal fistula into the gastrointestinal tract and causes obstruction, usually at the ileocecal valve. Bouveret syndrome is a variant of gallstone ileus where the gallstone lodges in the duodenum or pylorus causing a gastric outlet obstruction. The endoscopic and surgical management of this process are important to keep in mind and may be evolving as endoscopic therapies improve.

Single incision laparoscopic ventral hernia repair.

BACKGROUND AND OBJECTIVES: Laparoscopic ventral hernia repair (LVH) requires several skin incisions for trocar placement. We have developed a single incision approach to LVH repair. The technique was introduced in clinical practice to any consenting patients who were candidates for a standard multi-port laparoscopic hernia repair. A consecutive series of patients was then followed to evaluate feasibility. METHODS: Over an 8-month period, 14 patients (9 females, 5 males) underwent LVH repair by an academic surgeon. One of 2 access methods was used in each patient through a single 1.5-cm to 2-cm skin incision. One technique utilized two 5-mm ports with a temporarily placed 11-mm port for mesh insertion. The second technique utilized the SILS port (Covidien, Norwalk, CT). Standard or roticulating laparoscopic instruments were used with both techniques. RESULTS: Range (mean) BMI: 23 to 59 (38), Age: 26 to 73 years (53), DURATION: 37 to 87 minutes (57), Defect size: 1cm to 8cm (2), 3 with Swiss-cheese defect hernias. The procedure was successfully performed in all patients. No conversions to a multiple-port approach or to an open procedure were necessary. There were no mortalities, major complications, or recurrences during the mean follow-up period of 4 weeks. CONCLUSION: Single incision ventral hernia repair is technically feasible, effective, and reproducible. The technique is easy to master, and safe for any patient who is a candidate for laparoscopic ventral hernia repair. Further data collection with long-term follow-up will be needed to ensure equivalent outcomes. There will be demand for this approach by patients for cosmetic reasons, and it may serve as a bridge to natural orifice techniques.

Comparison of surgical residency applicants from U.S. medical schools with U.S.-born and foreign-born international medical school graduates.

OBJECTIVE: Compare characteristics of U.S. medical school graduates with U.S.-born and foreign-born international medical school (IMG) graduates. DESIGN: Retrospective analysis. SETTING: East Carolina University, a tertiary care teaching hospital. PARTICIPANTS: Demographic data, United States Medical Licensing Examination (USMLE) scores, attempts needed to achieve a passing score, number of scholarly works, attainment of an advanced degree, and employment history since medical school graduation were obtained from all Electronic Residency Application Service applications to a general surgery residency for the 2007 match. RESULTS: In all, 572 applicants were evaluated. Comparing U.S. graduates with U.S.-born IMGs and foreign-born IMGs. IMGs are older (mean, 28.9 vs 29.9 vs 33.0 years, respectively), more frequently male (70% vs 80% vs 86%, respectively), and hold more advanced degrees (11% vs 13% vs 19%, respectively). Mean time between graduation and application to residency was 0.3 years for U.S. graduates, 1.5 years for U.S.-born IMGs, and 7.7 years for foreign-born IMGs. Although mean USMLE Step 1 scores were similar (206 vs 200 vs 202, respectively), IMGs more frequently required multiple attempts to achieve a passing score (9% vs 20% vs 24%, respectively). Mean USMLE Step 2 scores were lower (213 vs 201 vs 203, respectively), and IMGs again required more attempts to achieve a passing score (11% vs 22% vs 19%, respectively). U.S. graduates produced an average of 1.7 scholarly works compared with 0.9 scholarly works for U.S.-born IMGS and 3.9 scholarly works for foreign-born IMGs. U.S.-born graduates held a mean of 0.3 jobs since graduation with most positions being preliminary surgery residents. U.S.-born IMGs held an average of 2.2 jobs most frequently in research or U.S. preliminary surgery, and foreign-born IMGs held an average of 5.1 jobs; most frequently, positions included international surgery or research. CONCLUSION: IMGs are older, frequently male, hold more advanced degrees, and produce more scholarly works but require multiple attempts to pass the USMLE. IMGs also hold more jobs after graduation with most positions being in research or surgery.