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BACKGROUND Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. METHODS We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less. RESULTS The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13-0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization. CONCLUSION For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. LEVEL OF EVIDENCE Prognostic/epidemiology study, level III.

The Emergency General Surgery (EGS) population is particularly at high risk for readmission. Currently, no system exists to predict which EGS patients are most at risk. We hypothesized that a subset of EGS patients could be identified with increased 30-day unplanned readmission. We also hypothesized that a majority of readmissions occur sooner than the conventional 2-week follow-up period.National Surgical Quality Improvement Program (NSQIP) nonelective general surgery patients were analyzed. Multivariable logistic regression identified factors with increased odds of unplanned readmission. AAST EGS Diagnosis Categories were used to categorize postop ICD-9 codes, and the top 10 CPT codes in each group were analyzed. Readmission rate, the reason for unplanned readmission, and time to readmission were analyzed.A total of 383,726 patients were identified with a readmission rate of 8.1% within 30 d of their primary procedure. The top 50 CPT codes accounted for 84% of EGS readmissions. Increased readmission risk was demonstrated for underweight patients (OR = 1.15, P 0.05). High-risk hospital characteristics were LOS2 d, any inpatient pulmonary complications, and discharge to any facility or rehab (all P 0.05). Surgical site infections cause nearly 25% of readmissions. Intestinal procedures are most frequently readmitted (22% of EGS readmissions), with colorectal procedures having the higher odds of readmission. Most readmissions occur10 d after discharge.A high-risk subpopulation exists within EGS, and most readmissions occur sooner than a typical 2-week follow-up. Early interventions for high-risk EGS subpopulations may allow for early intervention and reduction of unnecessary healthcare utilization.

Adhesive small bowel obstruction (ASBO) has classically been managed with nasogastric tube decompression and watchful waiting. Our group developed an evidence-based protocol to manage ASBO utilizing a water-soluble contrast (WSC) agent. We hypothesized the protocol would decrease the length of stay (LOS) for patients admitted with ASBO along with the time interval from admission to surgery.From 2010 to 2018, a retrospective review was performed, including all patients admitted with a diagnosis of ASBO. These patients were divided into two groups: the preprotocol group included years 2010-2013 and the postprotocol group included years 2015-2018. A Student t-test and a two-proportion z-test were used for statistical analysis.We captured 767 patients; 296 in the preprotocol group and 471 in the postprotocol group. We found a significant decrease in overall LOS between the preprotocol and postprotocol groups (6.56 d versus 4.08 d; P 0.001) along with decreases in LOS for patients managed nonoperatively (5.36 d versus 3.42 d; P 0.001) and operatively (16.09 d versus 9.47 d; P 0.001). Time interval from admission to the operation was significantly decreased in the postprotocol group (3.79 d versus 2.10 d; P 0.050). We identified a trend toward decreased rates of bowel ischemia and resections with our protocol.These results reaffirm previous reports of WSC's impact on overall LOS in ASBO while showing a similar impact on both operative and nonoperative groups. The decreased time interval between admission and operation may impact the incidence of bowel ischemia and resections.

Emergency general surgery (EGS) patients have increased mortality risk compared with elective counterparts. Recent studies on risk factors have largely used national data sets limited to administrative data. Our aim was to examine risk factors in an integrated regional health system EGS database, including clinical and administrative data, hypothesizing that this novel process would identify clinical variables as important risk factors for mortality.Our nine-hospital health system's billing data were queried for EGS International Classification of Disease codes between 2013 and 2018. Codes were grouped by diagnosis, and urgent or emergent encounters were included and merged with electronic medical record clinical data. Outcomes assessed were inpatient and 1-year mortality. Standard and multivariable statistics evaluated factors associated with mortality.There were 253,331 EGS admissions with 3.6% inpatient mortality rate. Patients who suffered inpatient and 1-year mortality were older, more likely to be underweight, and have neutropenia or elevated lactate. On multivariable analysis for inpatient mortality: age (odds ratio [OR], 1.7-6.7), underweight body mass index (OR, 1.6), transfer admission (OR, 1.8), leukopenia (OR, 2.0), elevated lactate (OR, 1.8), and ventilator requirement (OR, 7.1) remained associated with increased risk. Adjusted analysis for 1-year mortality demonstrated similar findings, with highest risk associated with older age (OR, 2.8-14.6), underweight body mass index (OR, 2.3), neutropenia (OR, 2.0), and tachycardia (OR, 1.7).After controlling for patient and disease characteristics available in administrative databases, clinical variables remained significantly associated with mortality. This novel yet simple process allows for easy identification of clinical data points imperative to the study of EGS diagnoses that are critical in understanding factors that impact mortality.Prognostic and Epidemiologic; Level III.

Background Recent antibiotic exposure has previously been associated with poor outcomes following elective surgery. The purpose of this study is to evaluate the impact of prior recent antibiotic exposure in a multicenter cohort of Veterans Affairs patients undergoing elective non-colorectal surgery. Methods This is a retrospective cohort study of the Veterans Affairs Surgical Quality Improvement Program, including elective, non-cardiovascular, non-colorectal surgery from 2013 to 2017. Outpatient antibiotic exposure within 90 days prior to surgery was identified from the Veterans Affairs outpatient pharmacy database and matched with each case. Primary outcomes included serious complication, any complication, any infection, or surgical site infection. Secondary outcomes included 30-day mortality, length of stay, and Clostridioides difficile infection. Results Of 21,112 eligible patients, 2885 (13.7%) were exposed to antibiotics within 90 days prior to surgery with a duration of 7 (IQR: 5-10) days and prescribed 42 (IQR: 21-64) days prior to surgical intervention. Compared to non-exposed patients, exposed patients had higher unadjusted complication rates, increased length of stay, and rates of return to the operating. Exposure was independently associated with return to the operating room (OR: 1.39; 99% CI: 1.05-1.84). Conclusions Among Veterans, recent antibiotic exposure within 90 days of elective surgery was associated with a 39% increase in the odds of return to the operating room. Further work is needed to evaluate the effects of antibiotic exposure and dysbiosis on surgical outcomes.

Background Operative management of emergency general surgery (EGS) diagnoses involves a range of procedures which can carry high morbidity and mortality. Little is known about the impact of obesity on patient outcomes. The aim of this study was to examine the association between body mass index (BMI) >30 kg/m2 and mortality for EGS patients. We hypothesized that obese patients would have increased mortality rates. Methods A regional integrated health system EGS registry derived from The American Association for the Surgery of Trauma EGS ICD-9 codes was analyzed from January 2013 to October 2015. Patients were stratified into BMI categories based on WHO classifications. The primary outcome was 30-day mortality. Longer-term mortality with linkage to the Social Security Death Index was also examined. Univariate and multivariable analyses were performed. Results A total of 60 604 encounters were identified and 7183 (11.9%) underwent operative intervention. Patient characteristics include 53% women, mean age 58.2 ± 18.7 years, 64.2% >BMI 30 kg/m2, 30.2% with chronic obstructive pulmonary disease, 19% with congestive heart failure, and 31.1% with diabetes. The most common procedure was laparoscopic cholecystectomy (36.4%). Overall, 90-day mortality was 10.9%. In multivariable analysis, all classes of obesity were protective against mortality compared to normal BMI. Underweight patients had increased risk of inpatient (OR = 1.9, CI = 1.7-2.3), 30-day (OR = 1.9, CI = 1.7-2.1), 90-day (OR = 1.8, CI 1.6-2.0), 1-year (OR = 1.8, CI = 1.7-2.0), and 3-year mortality (OR = 1.7, CI = 1.6-1.9). Conclusions When stratified by BMI, underweight EGS patients have the highest odds of death. Paradoxically, obesity appears protective against death, even when controlling for potentially confounding factors. Increased rates of nonoperative management in the obese population may impact these findings.

Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy characterized by early loco-regional invasion. Portal vein resection (PVR) during pancreatoduodenectomy (PD) for PDAC is performed if tumor cell invasion to the venous wall (PVI) is suspected. The aim of this study is to evaluate radiological criteria for predicting PVR and PVI. Methods Patients undergoing PD for PDAC were identified from a prospectively maintained database. On the basis of CT- and MRI-based imaging portal vein tumor contact (PV), stranding of the superior mesenteric artery (SMA) and any alterations of the superior mesenterico-portal vein (SMPV) were evaluated. The accuracy of PVI and PVR prediction based on the radiological parameters was calculated. Results 143 patients were included in the study. 48 patients underwent PVR (34%), PVI was diagnosed in 23 patients (16%). Median overall survival was 22 months. Prediction of PVR (sensitivity 79%, negative predictive value 88%, p = 0.010) and PVI (sensitivity 95%, negative predictive value 99%, p = 0.002) was most accurate for any SMPV alterations as compared to the other radiological parameters. SMPV alterations qualified as an independent prognostic parameter (26.5 months vs. 33.5months, p = 0.034). Conclusion Radiological evaluation of any SMPV alterations is a simple preoperative method to accurately predict PVI. Assessing SMPV alterations may help to identify candidates for neoadjuvant therapy.

Background Ventilator-associated pneumonia is poorly understood in trauma. Ventilated trauma patients can develop bacterial burden without symptoms; the factors that influence this are unknown. Methods Injured adults ventilated for > 2 days were enrolled. Mini-bronchoalveolar lavage was performed for 14 days or until extubation. Semi-quantitative cultures were blinded from clinicians. All cultures with > 104 colony forming units (CFU) were assessed for antibiotic exposure (ABXE) and spectrum of coverage. mBAL CFU was assessed daily. Results 60 patients were ventilated for 9 days (median). There were 75 with > 104 CFU. 46 had > 104 CFU and no ABXE on the sample day. 74% had clearance or a decrease (CoD) in CFU without ABXE. 29 had > 104 CFU and ABXE on the sample day. 19 had ABXE with pathogen coverage. 84% had CoD in CFU. 10 had ABXE with no spectrum of coverage. 1/10 had increased CFU and the remaining 9/10 CoD in CFU. The three groups were not statistically different on chi-squared analysis. Conclusion Clearance of pathogens on surveillance cultures was unaffected by ABXE.

Background: Surgical research is potentially invasive, high-risk, and costly. Research that advances medical dogma must justify both its ends and its means. Although ethical questions do not always have simple answers, it is critically important for the clinician, researcher, and patient to approach these dilemmas and surgical research in a thoughtful, conscientious manner. Methods: We present four ethical issues in surgical research and discuss the opposing viewpoints. These topics were presented and discussed at the 39th Annual Meeting of the Surgical Infection Society as pro–con debates. The presenters of each opinion developed a succinct summary of their respective reviews for this publication. Results: The key subjects for these pro–con debates were: (1) Should patients be enrolled for time-sensitive surgical infection research using an opt-out or an opt-in strategy? (2) Should patients who are being enrolled in a randomized controlled trial (RCT) comparing surgery with a non-operative intervention pay the costs of their treatment arm? (3) Should the scientific community embrace open access journals as the future of scientific publishing? (4) Should the majority of funding go to clinical or basic science research? Important points were illustrated in each of the pro–con presentations and illustrated the difficulties that are facing the performance and payment of infection research in the future. Conclusions: Surgical research is ethically complex, with conflicting demands between individual patients, society, and healthcare economics. At present, there are no clear answers to these and the many other ethical issues facing research in the future. Answers will only come from continued robust dialogue among all stakeholders in surgical research.

Background Blood flow restriction exercise has increasingly broad applications among healthy and clinical populations. Ensuring the technique is applied in a safe, controlled, and beneficial way for target populations is essential. Individualized cuff pressures are a favored method for achieving this. However, there remains marked inconsistency in how individualized cuff pressures are applied. Objectives To quantify the cuff pressures used in the broader blood flow restriction exercise literature, and determine whether there is clear justification for the choice of pressure prescribed. Methods Studies were included in this review from database searches if they employed an experimental design using original data, involved either acute or chronic exercise using blood flow restriction, and they assessed limb or arterial occlusion pressure to determine an individualized cuff pressure. Methodologies of the studies were evaluated using a bespoke quality assessment tool. Results Fifty-one studies met the inclusion criteria. Individualized cuff pressures ranged from 30% to 100% arterial occlusion pressure. Only 7 out of 52 studies attempted to justify the individualized cuff pressure applied during exercise. The mean quality rating for all studies was 11.1 ± 1.2 out of 13. Conclusions The broader blood flow restriction exercise literature uses markedly heterogeneous prescription variables despite using individualized cuff pressures. This is problematic in the absence of any clear justification for the individualized cuff pressures selected. Systematically measuring and reporting all relevant acute responses and training adaptations to the full spectrum of BFR pressures alongside increased clarity around the methodology used during blood flow restriction exercise is paramount.

The aim of this study was to evaluate the impact of the COVID-19 pandemic on volume and outcomes of Acute Care Surgery patients, and we hypothesized that inpatient mortality would increase due to COVID+ and resource constraints.An American College of Surgeons verified Level I Trauma Center's trauma and operative emergency general surgery (EGS) registries were queried for all patients from Jan. 2019 to Dec. 2020. April 1st, 2020, was the demarcation date for pre- and during COVID pandemic. Primary outcome was inpatient mortality.There were 14,460 trauma and 3091 EGS patients, and month-over-month volumes of both remained similar (p 0.05). Blunt trauma decreased by 7.4% and penetrating increased by 31%, with a concomitant 25% increase in initial operative management (p 0.001). Despite this, trauma (3.7%) and EGS (2.9-3.0%) mortality rates remained stable which was confirmed on multivariate analysis; p 0.05. COVID + mortality was 8.8% and 3.7% in trauma and EGS patients, respectively.Acute Care Surgeons provided high quality care to trauma and EGS patients during the pandemic without allowing excess mortality despite many hardships and resource constraints.

Data on duration of antibiotics in patients managed with an open abdomen (OA) due to intra-abdominal infection (IAI) are scarce. We hypothesized that patients with IAI managed with OA rather than closed abdomen (CA) would have higher rates of secondary infections (SIs) independent of the duration of the antibiotic treatment.This was an observational, prospective, multicenter, international study of patients with IAI requiring laparotomy for source control. Demographic and antibiotic duration values were collected. Primary outcomes were SI (surgical site, bloodstream, pneumonia, urinary tract) and mortality. Statistical analysis included ANOVA, chi-square/Fisher's exact test, and logistic regression.Twenty-one centers contributed 752 patients. The average age was 59.6 years, 43.6% were women, and 43.9% were managed with OA. Overall mortality was 16.1%, with higher rates among OA patients (31.6% vs 4.4%, p0.001). OA patients had higher Sequential Organ Failure Assessment (4.7 vs 1.8, p0.001), American Society of Anesthesiologists Physical Status (3.6 vs 2.7, p0.001), and APACHE II scores (16.1 vs 9.4, p0.001). The mean duration of antibiotics was 6.5 days (8.0 OA vs 5.4 CA, p0.001). A total of 179 (23.8%) patients developed SI (33.1% OA vs 16.8% CA, p0.001). Longer antibiotic duration was associated with increased rates of SI: 1 to 2 days, 15.8%; 3 to 5 days, 20.4%; 6 to 14 days, 26.6%; and more than 14 days, 46.8% (p0.001).Patients with IAI managed with OA had higher rates of SI and increased mortality compared with CA. A prolonged duration of antibiotics was associated with increased rates of SI. Increased antibiotic duration is not associated with improved outcomes in patients with IAI and OA.

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA—a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Early selection steps preventing autoreactive naive B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc). This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc.Using an in vitro polymerase chain reaction-based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+CD21Compared to serum from healthy donors, serum from patients with SSc displayed elevated proportions of polyreactive and antinuclear-reactive new emigrant/transitional B cells that recognize topoisomerase I, suggesting that defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naive B cells were also significantly increased in SSc patients compared to healthy donors, thus indicating that a peripheral B cell tolerance checkpoint may be impaired in SSc.Defective counterselection of developing autoreactive naive B cells in SSc leads to the production of self antigen-specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.

BackgroundInterstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease.MethodsEligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program.Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George’s Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation.DiscussionThe standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease.Trial registrationClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019,https://clinicaltrials.gov/ct2/show/NCT03800914Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true

Background: Per the Centers for Medicare and Medicaid Services (CMS) Code of Federal Regulations (CFR) 482.23(c) regarding medication administration, hospital policies and procedures must identify time-critical scheduled medications which must be administered within 30 minutes either before or after the scheduled dosing time, for a total administration window of 1 hour. Objective: The general objective of this analysis was to determine whether there was a difference in meeting medication administration goals when comparing time-critical to non-time-critical scheduled medication administration in both intensive care units (ICUs) and general medical floors at a large, academic medical center. Methods: Data were collected in 6 inpatient nursing units (3 general medical units and 3 ICUs) during the month of June 2017. Electronic medical record charge data for medications were used to evaluate timeliness of medication administration. Results: In total, 69,794 medication administrations were evaluated. Of 389 administrations of time-critical scheduled medications, 268 (69%) were administered on time. Of 69,405 administrations of non-time-critical scheduled medications, 58,099 (84%) were administered on time ( P < 0.001). ICUs had a higher percentage of on-time administrations than general medical units (89% vs 77%, P < 0.001), and nurses had a higher percentage of on-time administrations than respiratory therapists (84% vs 63%, P < 0.001). Conclusions: Non-time-critical scheduled medications were more commonly administered on time compared with time-critical scheduled medications. Staff education and optimizations to the electronic health record (EHR) are interventions that may improve administration of time-critical scheduled medications.

Necrotizing soft-tissue infections are caused by a variety of bacterial pathogens that may affect patients at any age or health status. This orthopaedic emergency initially presents with nonspecific signs such as erythema and edema. As the disease progresses, classic signs such as bullae, cutaneous anesthesia, ecchymosis, tense edema, and gas can be seen. A high level of suspicion is needed to properly identify and treat in a timely manner. Pain out of proportion to presentation and rapid progression even with appropriate antibiotic treatment should heighten suspicion of a necrotizing soft-tissue infection. The mainstay of management is extensive débridement and decompression of all necrotic tissue and broad-spectrum antibiotics. Débridements are repeated to ensure that disease progression has been halted. Early surgical débridements should take precedent over transfer because of the high rate of limb loss and mortality as a result of surgical delay.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.

The aim of this study was to evaluate the use of laparoscopic surgery for common emergency general surgery (EGS) procedures within an integrated Acute Care Surgery (ACS) network. We hypothesized that laparoscopy would be associated with improved outcomes.Our integrated health care system's EGS registry created from AAST EGS ICD-9 codes was queried from January 2013 to October 2015. Procedures were grouped as laparoscopic or open. Standard descriptive and univariate tests were performed, and a multivariable logistic regression controlling for open status, age, BMI, Charlson Comorbidity Index (CCI), trauma tier, and resuscitation diagnosis was performed. Laparoscopic procedures converted to open were identified and analyzed using concurrent procedure billing codes across episodes of care.Of 60,604 EGS patients identified over the 33-month period, 7280 (12.0%) had an operation and 6914 (11.4%) included AAST-defined EGS procedures. There were 4813 (69.6%) surgeries performed laparoscopically. Patients undergoing a laparoscopic procedure tended to be younger (45.7 ± 18.0 years vs. 57.2 ± 17.6, p 0.001) with similar BMI (29.7 ± 9.0 kg/mUse of laparoscopy in EGS is common and associated with a decreased risk of all-cause mortality at all time points compared to open procedures. Conversion to open was protective at all time points compared to open procedures.

Individuals with developmental disabilities (DD) are twice as likely to have obesity than non-disabled individuals. Replacing the consumption of sugar sweetened beverages (SSBs) with water has many health benefits, including weight reduction. In this study, a token reinforcement system was implemented to increase water consumption and decrease the consumption of SSBs with 14 adult participants with DD living in a community-based independent supported living (ISL) center. Token reinforcement reduced the consumption of SSBs, with associated reductions in calorie consumption and body weight. Findings are especially important for treatment settings where resources for individualized meal planning and staffing to support comprehensive behavioral interventions may be limited.

Electrophilic heterocycles offer attractive features as covalent fragments for inhibitor and probe development. A focused library of heterocycles for which protonation can enhance reactivity (called "switchable electrophiles") is screened for inhibition of the proposed drug target dimethylarginine dimethylaminohydrolase (DDAH). Several novel covalent fragments are identified: 4-chloroquinoline, 4-bromopyridazine, and 4,4-dipyridylsulfide. Mechanistic studies of DDAH inactivation by 4,4-dipyridylsulfide reveal selective covalent S-pyridinylation of the active-site Cys through catalysis by a neighboring Asp residue. Inactivation (kinact/KI = 0.33 M-1 s-1) proceeds with release of 4-thiopyridone (0.78 equiv), and structure-activity relationships reveal that the leaving group pKa can be modulated to tune reactivity. The use of a "switchable electrophile" strategy helps impart selectivity, even to fragment-sized modifiers. Identification of 4,4-dipyridylsulfide analogs as inactivators offers an easily tunable covalent fragment with multiple derivatization sites on both the leaving and staying groups.

Background Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) can be associated with severe postoperative morbidity. This study aims to develop a preoperative POPF risk calculator that can be easily implemented in clinical routine. Methods Patients undergoing PD were identified from a prospectively-maintained database. A total of 11 preoperative baseline and CT-based radiological parameters were used in a binominal logistic regression model. Parameters remaining predictive for grade B/C POPF were entered into the risk calculator and diagnostic accuracy measures and ROC curves were calculated for a training and a test patient cohort. The risk calculator was transformed into a simple nomogram. Results A total of 242 patients undergoing PD in the period from 2012 to 2018 were included. CT-imaging-based maximum main pancreatic duct (MPD) diameter (p = 0.047), CT-imaging-based pancreatic gland diameter at the anticipated resection margin (p = 0.002) and gender (p = 0.058) were the parameters most predictive for grade B/C POPF. Based on these parameters, a risk calculator was developed to identify patients at high risk of developing grade B/C POPF. In a training cohort of PD patients this risk calculator was associated with an AUC of 0.808 (95%CI 0.726–0.874) and an AUC of 0.756 (95%CI 0.669-0-830) in the independent test cohort. A nomogram applicable as a visual risk scale for quick assessment of POPF grade B/C risk was developed. Conclusion The preoperative POPF risk calculator provides a simple tool to stratify patients planned for PD according to the risk of developing postoperative grade B/C POPF. The nomogram visual risk scale can be easily integrated into clinical routine and may be a valuable model to select patients for POPF-preventive therapy or as a stratification tool for clinical trials.

Background: Previous estimates of the incidence of necrotizing soft tissue infections (NSTI) in the United States have substantial limitations and underestimate its occurrence. Improvements in hosp...

Objectives: To identify exercise tests that are suitable for home-based or remote administration in people with chronic lung disease. Methods: Rapid review of studies that reported home-based or remote administration of an exercise test in people with chronic lung disease, and studies reporting their clinimetric (measurement) properties. Results: 84 studies were included. Tests used at home were the 6-minute walk test (6MWT, two studies), sit-to-stand tests (STS, five studies), Timed Up and Go (TUG, 4 studies) and step tests (two studies). Exercise tests administered remotely were the 6MWT (two studies) and step test (one study). Compared to centre-based testing the 6MWT distance was similar when performed outdoors but shorter when performed at home (two studies). The STS, TUG and step tests were feasible, reliable (intra-class correlation coefficients >0.80), valid (concurrent and known groups validity) and moderately responsive to pulmonary rehabilitation (medium effect sizes). These tests elicited less desaturation than the 6MWT, and validated methods to prescribe exercise were not reported. Discussion: The STS, step and TUG tests can be performed at home, but do not accurately document desaturation with walking or allow exercise prescription. Patients at risk of desaturation should be prioritised for centre-based exercise testing when this is available.

We examined the concurrent characteristics of the remote development of strength and cross-sectional area (CSA) of upper body skeletal muscle in response to lower body resistance training performed with an applied blood flow restriction (BFR).Males allocated to an experimental BFR group (EXP; n = 12) or a non-BFR control group (CON; n = 12) completed 7-weeks of resistance training comprising three sets of unilateral bicep curls [50% 1-repetition maximum (1-RM)], then four sets of bilateral knee extension and flexion exercises (30% 1-RM). EXP performed leg exercises with an applied BFR (60% limb occlusion pressure). 1-RM strength was measured using bilateral leg exercises and unilateral bicep curls in both trained and untrained arms. Muscle CSA was measured via peripheral quantitative computed tomography in the dominant leg and both arms.1-RM in the trained arm increased more in EXP (2.5 ± 0.4 kg; mean ± SEM) than the contralateral untrained arm (0.8 ± 0.4 kg), and the trained arm of CON (0.6 ± 0.3 kg, P 0.05). The increase in knee extension 1-RM was twofold that of CON (P 0.01). Knee flexion 1-RM, leg CSA, and trained arm CSA increased similarly between groups (P 0.05), while untrained arm CSA did not change (P 0.05).Lower limb BFR training increased trained arm strength more than the contralateral untrained arm, and the trained arm of controls. However, there was no additional effect on muscle CSA. These findings support evidence for a BFR training-derived remote strength transfer that may be relevant to populations with localised movement disorders.

The optimal duration of antimicrobial therapy for treatment of complicated intra-abdominal infections (cIAI) in critically ill surgical patients is unknown. Recent evidence suggests that a short (four-day) course of therapy may be effective, however data in severely critically ill patients are limited.A single-center, retrospective, cohort study was conducted at a tertiary academic medical center. Adult patients admitted to the surgical intensive care unit (SICU) with cIAI between December 2011 and July 2015 were enrolled. Patients undergoing transplantation and those with less than 24 h in the SICU were excluded. Patients were divided into two groups, short (≤ 7 d) and long (7 d) antimicrobial therapy. The primary outcome was treatment failure, which was defined as a composite of recurrent cIAI, secondary extra-abdominal infection, and/or in-hospital mortality from any cause. Categorical and continuous data were analyzed with χOf 1,679 patients screened, 240 were included, 103 in the short and 137 in the long group. Patients in the short and long groups received a median of 5 and 14 d of therapy, respectively (p 0.001). Treatment failure occurred less frequently with a short duration of therapy (39% versus 63%, p 0.001) and it occurred two days sooner after source control in patients receiving the shorter courses of antimicrobial therapy (short, median 6 d, interquartile range [IQR] 3-9; long, 8 d, IQR 6-14; p 0.001). Logistic regression demonstrated that a long duration of therapy was associated with treatment failure (odds ratio [OR] 2.186, 95% confidence interval [CI] 1.251-3.820, p = 0.006), but not with mortality (OR 0.738, 95% CI 0.329-1.655, p = 0.461).In critically ill surgical patients with cIAI, a short duration of antimicrobial therapy after source control resulted in similar outcomes to previously published studies, providing support for the safety of this approach in critically ill patients.

Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27&ndash, 40 weeks&rsquo, gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A &amp, cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings, total creatine content of PE placentae was 38% higher than controls (p &lt, 0.01). mRNA expression of GATM (p &lt, 0.001), GAMT (p &lt, 0.001), SLC6A8 (p = 0.021) and BBCK (p &lt, 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.

Background Emergency surgical services often encounter patients with generalized peritonitis. Difficult perioperative decisions impact morbidity, mortality, cost, and utilization of hospital resources. The ability to preoperatively predict patient nonsurvival despite surgical intervention using clinical physiologic indicators was the aim of this study and would be helpful in counseling patients/families. Methods A retrospective cohort from an institutional database was queried for nontrauma patients with peritonitis undergoing emergency laparotomy from 2012 to 2016. Time to mortality after surgery was compared: early (≤72 hours) versus late (>72 hours) and no death. Results After 534 emergency laparotomies, there were 74 (13.9%) mortalities. Of these, death occurred early (≤72 hours) after surgery in 28 (37.8%) patients and late (>72 hours) in 46 (62.2%). Early death patients had a significantly more deranged physiology, as evidenced by higher Acute Physiology and Chronic Health Evaluation II scores (mean 28.1 ± 8.4 vs 22.9 ± 8.7, P = .01), worse acute kidney injury (preoperative creatinine 3.7 ± 3.2 vs 1.9 ± 1.4, P = .001), and greater level of acidosis (pH 7.19 ± 0.12 vs 7.27 ± 0.13, P = .017). Additionally, preoperative lactate was significantly increased in patients with early mortality (6.8 ± 4.1 vs 5.1 ± 4.0, P = .045). Using logarithmic regression, a nomogram was constructed using age, Glasgow Coma Scale, lactate, creatinine, and pH. This nomogram had an area under the curve of 0.908 on receiver operator curve analysis. A score of 13 equates to greater than 50% risk of early mortality after surgery. Conclusion Early mortality (≤72 hours after emergency laparotomy) is associated with decreased pH, elevated creatinine, and elevated lactate. These factors combined into the nomogram constructed may assist surgical teams with patient and family discussions to prevent futile surgical interventions.

Background Reflection spectroscopy is an emerging, non-invasive objective measure used to approximate fruit and vegetable intake. The present study aimed to use a reflection spectroscopy device (the Veggie Meter®, Longevity Link Corporation, Salt Lake City, UT, USA) to assess skin carotenoid status in preschool, middle- and high-school students and to examine associations between skin carotenoids and self-reported dietary intake. Methods In Autumn 2018, we used the Veggie Meter® to assess skin carotenoids and age-appropriate validated dietary assessment measures to approximate fruit and vegetable (FV) intake. Preschool participants completed a previously validated pictorial liking tool using an iPad (Apple Inc., Cupertino, CA, USA). Middle-school participants completed selected questions from the validated School Physical Activity and Nutrition (SPAN) (Michael & Susan Dell Center for Healthy Living, University of Texas, Austin, TX, USA) questionnaire regarding frequency of their FV and beverage intake on the previous day, with additional questions about physical activity. High-school participants' FV intake was assessed using the Fruit and Vegetable Screener (National Cancer Institute, Bethesda, MD, USA). Spearman correlation coefficients were used to determine bivariate associations between measures of dietary intake and Veggie Meter®-assessed skin carotenoid levels. Results Mean (SD) Veggie Meter® readings were 266 (82.9), 219 (68.1) and 216 (67.2) among preschool, middle- and high-school students. There was an inverse association between soda intake and Veggie Meter® readings (r = -0.22, P = 0.03) among middle-school students; and a positive association between daily fruit intake and Veggie Meter® readings (r = 0.25, P = 0.06) among high-school students. Conclusions The Veggie Meter® comprises a promising evaluation tool for preschool and school-based nutrition interventions.

BACKGROUND The lymphocyte-depleting antibody alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS); however, 50% of patients develop novel autoimmunity after treatment. Most at risk are individuals who reconstitute their T cell pool by proliferating residual cells, rather than producing new T cells in the thymus, raising the possibility that autoimmunity might be prevented by increasing thymopoiesis. Keratinocyte growth factor (palifermin) promotes thymopoiesis in nonhuman primates. METHODS Following a dose tolerability substudy, individuals with RRMS (duration ≤10 years; expanded disability status scale ≤5.0, with ≥2 relapses in the previous 2 years) were randomized to placebo or 180 μg/kg/d palifermin, given for 3 days immediately before and after each cycle of alemtuzumab, with repeat doses at month 1 (M1) and M3. The interim primary endpoint was naive CD4+ T cell count at M6. Exploratory endpoints included number of recent thymic emigrants (RTEs) and signal joint T cell receptor excision circles/ml (sjTRECs/ml) of blood. The trial’s primary endpoint was incidence of autoimmunity at M30. RESULTS At M6, individuals receiving palifermin had fewer naive CD4+ T cells (2.229 × 107/l vs. 7.733 × 107/l; P = 0.007), RTEs (16% vs. 34%), and sjTRECs/ml (1100 vs. 3396), leading to protocol-defined termination of recruitment. No difference was observed in the rate of autoimmunity between the 2 groups. CONCLUSION In contrast with animal studies, palifermin reduced thymopoiesis in our patients. These results offer a note of caution to those using palifermin to promote thymopoiesis in other settings, particularly in the oncology/hematology setting, where alemtuzumab is often used as part of the conditioning regime. TRIAL REGISTRATION ClinicalTrials.gov NCT01712945. FUNDING MRC and Moulton Charitable Trust., Keratinocyte growth factor impairs T cell recovery in patients with relapsing-remitting multiple sclerosis receiving treatment with the lymphocyte-depleting monoclonal antibody alemtuzumab.

Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate—GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.

Different forms of nuclear envelope–spanning LINC complexes have opposing roles in the transcription-independent control of the small GTPase RhoA. Competition between LINC complexes in the nuclear envelope may therefore dictate the outcome of signaling to cytoskeletal networks., Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA.

Despite current antimicrobial stewardship programs (ASPs) being advocated by infectious disease specialists and discussed by national and international policy makers, ASPs coverage remains limited to only certain hospitals as well as specific service lines within hospitals. The ASPs incorporate a variety of strategies to optimize antimicrobial agent use in the hospital, yet the exact set of interventions essential to ASP success remains unknown. Promotion of ASPs across clinical practice is crucial to their success to ensure standardization of antimicrobial agent use within an institution. To effectively accomplish this standardization, providers who actively engage in antimicrobial agent prescribing should participate in the establishment and support of these programs. Hence, surgeons need to play a major role in these collaborations. Surgeons must be aware that judicious antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize emergence of antimicrobial resistance. The battle against antibiotic resistance should be fought by all healthcare professionals. If surgeons around the world participate in this global fight and demonstrate awareness of the major problem of antimicrobial resistance, they will be pivotal leaders. If surgeons fail to actively engage and use antibiotics judiciously, they will find themselves deprived of the autonomy to treat their patients.

To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients.GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients.A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints.Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar.PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

The novel coronavirus (COVID-19) was first diagnosed in Wuhan, China in December 2019 and has now spread throughout the world, being verified by the World Health Organization as a pandemic on March 11. This had led to the calling of a national emergency on March 13 in the US. Many hospitals, healthcare networks, and specifically, departments of surgery, are asking the same questions about how to cope and plan for surge capacity, personnel attrition, novel infrastructure utilization, and resource exhaustion. Herein, we present a tiered plan for surgical department planning based on incident command levels. This includes acute care surgeon deployment (given their critical care training and vertically integrated position in the hospital), recommended infrastructure and transfer utilization, triage principles, and faculty, resident, and advanced care practitioner deployment.

To develop an early warning discharge disposition prediction tool based on clinical and health services factors for hospitalized patients. Recent study results suggest that early prediction of discharge disposition (ie, whether patients can return home or require placement in a facility) can improve care coordination, expedite care planning, and reduce length of stay.Retrospective analysis of inpatient data; development of multiple logistic regression model and an easy-to-use score.We used retrospective data from all patients who were admitted in 2013 to the general medical service at the Veterans Affairs Boston Healthcare System and discharged alive. A derivation-validation approach was used to build a multiple logistic regression model, which was transformed into a score for potential implementation.Of the 4760 patients discharged in 2013, 485 (10.2%) were discharged to a facility other than home. Correlates of discharge to a facility included a primary admission diagnosis of neoplasm (odds ratio [OR], 2.71; 95% CI, 1.73-4.25), diseases of the nervous system (OR, 2.53; 95% CI, 1.26-5.08), and musculoskeletal diseases (OR, 2.55; 95% CI, 1.52-4.27), as well as discharge to a facility during previous hospitalization. Patients with a prior primary diagnosis of circulatory disorder and those with comorbidity of hypertension, either complicated or uncomplicated, were less likely to be discharged to a facility. A value of 5 or greater on the 20-point scale indicated discharge to a facility with 83% sensitivity and 48% specificity.A validated, easy-to-use score can assist providers in identifying upon admission those patients who may not be able to go directly home after hospitalization, thus facilitating early discharge planning and coordination, potentially reducing length of hospital stay and improving patient experience.

BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration among critically ill adults. Which results in better clinical outcomes remains unknown. METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A®), according to the randomization of the unit to which they were admitted. The primary outcome was Major Adverse Kidney Events within 30 days (MAKE30), i.e., the composite of death, new renal replacement therapy, or persistent creatinine elevation ≥ 200% of baseline – all censored at the first of hospital discharge or 30 days. RESULTS: In the balanced crystalloid group, 1,139 patients (14.3%) experienced MAKE30, compared to 1,211 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval, 0.84–0.99; conditional odds ratio, 0.90; 95% confidence interval, 0.82–0.99; P=0.04). Thirty-day in-hospital mortality was 10.3% in the balanced crystalloid group and 11.1% in the saline group (P=0.06). The incidence of new renal replacement therapy was 2.5% and 2.9% respectively (P=0.08), and the incidence of persistent creatinine elevation was 6.4% and 6.6% respectively (P=0.60). CONCLUSIONS: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration appeared to reduce the composite outcome of in-hospital mortality, new renal replacement therapy, and persistent renal dysfunction compared with the use of saline. (SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)

Background: Ventilator-associated pneumonia (VAP) is common in critically injured patients. The pathogenesis of VAP is not completely understood. We hypothesized that mechanically ventilated trauma patients who develop pneumonia have a progressive increase in pathogen burden over the course of ventilation until a threshold for symptomatic pneumonia is reached, leading to clinical suspicion of VAP. Methods: Critically injured adults ventilated for more than two successive days were enrolled. Patients underwent daily surveillance mini-bronchoscopic alveolar lavage (mBAL) while ventilated for 14 days or until extubation. Standard semi-quantitative cultures were performed, and the investigators were blinded to the results. Standard patient management was performed by the clinical team. Patients suspected of having VAP by the clinical team underwent bronchoscopic bronchoalveolar lavage (bBAL) and semi-quantitative culture, with VAP defined as clinical symptoms plus >10(4) colony-forming units (CFU) of bacteria. Standard statistical analysis for non-parametric data was performed. Results: The 37 patients enrolled were ventilated for a median of nine days. While ventilated, 23 patients met the criteria for a clinical suspicion of VAP, of which two were too ill for bronchoscopy. Thus, 21 patients underwent bBALs because of a suspicion of VAP, and 13 (35%) were positive, with >10(4) CFU of one or more pathogens, and were treated for pneumonia. The bacterial burden on mBAL remained 10(4) CFU without clinical suspicion of VAP. Half (56%) of positive surveillance cultures were followed by clinical VAP, confirmed by bBAL, all of which had identical pathogens on mBAL and bBAL. Almost half (44%) of the patients with positive surveillance mBALs never developed clinical VAP. Conclusion: A significant percentage of critically injured, ventilated adults develop high bacterial burdens in the lungs early in their course, and many clear these bacteria without developing VAP. Further study is needed to identify the factors causing progression to VAP.

Injury is an external stressor that often initiates a cycle of decline in many older adults. The influence of physical frailty and cognitive decline on 6-month and 1-year outcomes after injury is unreported. We hypothesized that physical frailty and cognitive impairment would be predictive of 6-month and 1-year postinjury function and overall mortality.The sample involved patients who are 65 years or older admitted to a Level I trauma center between October 2013 and March 2014 with a primary injury diagnosis. Surrogates of 188 patients were interviewed within 48 hours of hospital admission to determine preinjury cognitive and physical frailty impairments using brief screening instruments. Follow-up was completed on 172 patients at 6 months and 176 patients at 1 year to determine posthospitalization status and outcomes. Data analysis involved frequencies, measures of central tendency, χ analyses, linear and logistic regression.The mean age of the patients was 77 years. The median Injury Severity Score (ISS) was 10. The mechanism of injury involved falls from standing (n = 101, 54%). Preinjury vulnerabilities included cognitive impairment (AD8 Dementia Screen [AD8] score ≥ 2, n = 93, 50%) and physical frailty (Vulnerable Elders Survey [VES-13] score ≥ 4, n = 94, 50%). Overall, median physical frailty scores did not return to baseline in the majority of survivors at 1 year. Multivariate regression analysis revealed that preinjury cognitive impairment (6 months, AD8, β = -0.20, p = 0.002) and preinjury physical frailty (6 months, Barthel Index, β = 0.60, p0.001; 1 year, Barthel Index, β = 0.52, p0.001) are independently associated with physical function (frailty). Multivariate logistic regression analysis revealed that age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.14), injury severity (OR, 1.07; 95% CI, 1.02-1.12), and preinjury physical frailty (OR, 1.28; 95% CI, 1.14-1.47) are independently associated with overall mortality at 1 year.Preinjury physical frailty is the predominant predictor of postinjury functional status and mortality in geriatric trauma patients. Identification of frailty and appropriate follow-up are crucial for decision making by providers, patients, and family caregivers.Prognostic study, level II.

Background Teaching hospitals often employ advanced practice providers (nurse practitioners and physician assistants or APPs) to counteract residents' work-hour restrictions. With increased utilization of APPs in labor-intense areas, such as intensive care units (ICUs), APPs may have an impact on resident education and experience. No studies have investigated the direct role an APP plays on the training experience of a surgical resident in the ICU. Materials and methods An institutional review board-approved survey was emailed to residents in Accreditation Council for Graduate Medical Education-accredited general surgery programs. Surveys asked about demographics, residency and/or ICU characteristics, and the effects of APPs on patient care, workflow, and educational experience. Regression analysis determined predictors of resident perception. Results A total of 354 of 1178 residents responded to the survey (30%). Some residents felt that nurses calling APPs preferentially for patient-care issues interfered with education (17%) and residents' ability to follow patients (12%) and was associated with overall detrimental effects to ICU experience on regression (odds ratio, 3.7; confidence interval, 1.5–9.1). Most residents reported positive effects of APPs, such as reduced resident workload (79.8%), teaching protocols and/or guidelines (60.3%), enhanced patient care (60.3%), and enhanced communication (50.5%). When asked how APPs affected their overall ICU experience, 48.4% reported positive effects, 20.6% reported “no effect,” and 31% reported detrimental effects. Conclusions Only a minority of residents perceived that APPs detract from training, particularly those who felt excluded when nurses preferentially contact APPs with patient-care issues. APPs have the potential to enhance training and ICU experience, as reflected in many of the responses. Strategies to maintain direct nurse and resident communication might preserve residents' perception of the educational value of APPs.

LInkers of Nucleoskeleton and Cytoskeleton (LINC) complexes, composed of SUN and KASH-domain proteins, span the nuclear envelope and physically connect the nuclear interior to cytoskeletal elements. Most human cells contain two SUN proteins, Sun1 and Sun2, and several KASH-proteins suggesting that multiple functionally distinct LINC complexes co-exist in the nuclear envelope. We show here, however, that while Sun1 and Sun2 in HeLa cells are each able to bind KASH-domains, Sun1 is more efficiently incorporated into LINC complexes under normal growth conditions. Furthermore, the balance of Sun1 and Sun2 incorporated into LINC complexes is cell type-specific and is correlated with SRF/Mkl1-dependent gene expression. In addition, we found that Sun1 has a LINC complex-independent role in transcriptional control, possibly by regulating the SRF/Mkl1 pathway. Together, these data reveal novel insights into the mechanisms of LINC complex regulation and demonstrate that Sun1 modulates gene expression independently of its incorporation into LINC complexes.

Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.

SummaryBackground: Hospital length of stay and discharge destination are important outcome measures in evaluating effectiveness and efficiency of health services. Although hospital administrative data are readily used as a data collection source in health services research, no research has assessed this data collection method against other commonly used methods.Objective: Determine if administrative data from electronic patient management programs are an effective data collection method for key hospital outcome measures when compared with alternative hospital data collection methods.Method: Prospective observational study comparing the completeness of data capture and level of agreement between three data collection methods; manual data collection from ward-based sources, administrative data from an electronic patient management program (i.PM), and inpatient medical record review (gold standard) for hospital length of stay and discharge destination. Results: Manual data collection from ward-based sources captured only 376 (69%) of the 542 in-patient episodes captured from the hospital administrative electronic patient management program. Administrative data from the electronic patient management program had the highest levels of agreement with inpatient medical record review for both length of stay (93.4%) and discharge destination (91%) data.Conclusion: This is the first paper to demonstrate differences between data collection methods for hospital length of stay and discharge destination. Administrative data from an electronic patient management program showed the highest level of completeness of capture and level of agreement with the gold standard of inpatient medical record review for both length of stay and discharge destination, and therefore may be an acceptable data collection method for these measures.Citation: Sarkies MN, Bowles K-A, Skinner EH, Mitchell D, Haas R, Ho M, Salter K, May K, Markham D, O’Brien L, Plumb S, Haines T.P. Data collection methods in health services research – hospital length of stay and discharge destination. Appl Clin Inf 2015; 6: 96–109http://dx.doi.org/10.4338/ACI-2014-10-RA-0097

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes.

Background & Aims There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome. Methods We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis. Results Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8–1.7) ( P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0–5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) ( P = .04). Conclusions In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.

Low-load resistance training with blood flow restriction has been shown to elicit substantial increases in muscle mass and muscle strength; however, the effect on myogenic stem cells (MSCs) and myonuclei number remains unexplored. Ten male subjects (22.8 ± 2.3 years) performed four sets of knee extensor exercise (20% 1RM) to concentric failure during blood flow restriction (BFR) of the proximal thigh (100 mmHg), while eight work-matched controls (21.9 ± 3.0 years) trained without BFR (control, CON). Twenty-three training sessions were performed within 19 days. Maximal isometric knee extensor strength (MVC) was examined pre- and post-training, while muscle biopsies were obtained at baseline (Pre), after 8 days intervention (Mid8) and 3 (Post3) and 10 days (Post10) post training to examine changes in myofibre area (MFA), MSC and myonuclei number. MVC increased by 7.1% (Post5) and 10.6% (Post12) (P < 0.001) with BFR training, while type I and II MFA increased by 38% (Mid8), 35–37% (Post3) and 31–32% (Post10) (P < 0.001). MSCs per myofibre increased with BFR training from 0.10 ± 0.01 (Pre) to 0.38 ± 0.02 (Mid8), 0.36 ± 0.04 (Post3) and 0.25 ± 0.02 (Post10) (P < 0.001). Likewise, myonuclei per myofibre increased from 2.49 ± 0.07 (Pre) to 3.30 ± 0.22 (Mid8), 3.20 ± 0.16 (Post3) and 3.11 ± 0.11 (Post10), (P < 0.01). Although MFA increased in CON at Mid8, it returned to baseline at Post3. No changes in MSC or myonuclei number were observed in CON. This study is the first to show that short-term low-load resistance exercise performed with partial blood flow restriction leads to marked proliferation of myogenic stem cells and resulting myonuclei addition in human skeletal muscle, which is accompanied by substantial myofibre hypertrophy.