Host Microbiome Threats in the Intensive Care Unit.

Human microbiota demonstrate diversity and balance that is adaptive for the host and supports maintaining homeostasis. Although acute illness or injury may derange microbiota diversity and the proportion of potentially pathogenic microbes, that derangement may be further exacerbated by commonly deployed intensive care unit (ICU) therapeutic and practices. These include antibiotic administration, delayed luminal nutrition, acid suppression, and vasopressor infusion. Furthermore, the local ICU microbial ecology, regardless of disinfection practices, shapes the patient's microbiota, especially with the acquisition of multi-drug-resistant pathogens. Current approaches to protect a normal microbiome, or restore a deranged one, are part of a multifaceted approach that may include antibiotic stewardship and infection control practices as microbiome-directed therapeutics emerge.

Sepsis and postoperative surgical site infections.

Surgical site infections remain a significant cause of morbidity and mortality. High-quality evidence supports several measures to prevent surgical site infections that should be applied with high compliance, although effective application remains suboptimal. Recognizing high-risk patients and avoiding potential pitfalls in the diagnosis of surgical site infections is paramount in preventing progression to sepsis, particularly in emergency surgical patients with physiologic derangement. A high index of suspicion postoperatively is critical to identify patients with surgical site infections and to prevent failure to rescue.

Emergency General Surgery Regionalization: Retrospective Cohort Study of Emergency General Surgery Patients at a Tertiary Care Center.

BACKGROUND: Emergency general surgery (EGS) patients presenting at tertiary care hospitals may bypass local hospitals with adequate resources. However, many tertiary care hospitals frequently operate at capacity. We hypothesized that understanding patient geographic origin could identify opportunities for enhanced system triage and optimization and be an important first step for EGS regionalization and care coordination that could potentially lead to improved utilization of resources. METHODS: We analyzed patient zip code and categorized EGS patients who were cared for at our tertiary care hospital as potentially divertible if the southern region hospital was geographically closer to their home, regional hospital admission (RHA) patients, or local admission (LA) patients if the tertiary care facility was closer. Baseline characteristics and outcomes were compared for RHA and LA patients. RESULTS: Of 14 714 EGS patients presenting to the tertiary care hospital, 30.2% were categorized as RHA patients. Overall, 1526 (10.4%) patients required an operation including 527 (34.5%) patients who were potentially divertible. Appendectomy and cholecystectomy comprised 66% of the operations for potentially divertible patients. Length of stay was not significantly different (P = .06) for RHA patients, but they did have lower measured short-term and long-term mortality when compared to their LA counterparts (P < .05). CONCLUSIONS: EGS diagnoses and patient geocode analysis can identify opportunities to optimize regional operating room and bed utilization. Understanding where EGS patients are cared for and factors that influenced care facility will be critical for next steps in developing EGS regionalization within our system.

Emergencies do not shut down during a pandemic: COVID pandemic impact on Acute Care Surgery volume and mortality at a level I trauma center.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The physiology of failure: Identifying risk factors for mortality in emergency general surgery patients using a regional health system integrated electronic medical record.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Prior Antibiotic Exposure Is Associated With Reoperation After Elective Non-colorectal Surgery.

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.

Effect of Antibiotic Duration in Emergency General Surgery Patients with Intra-Abdominal Infection Managed with Open vs Closed Abdomen.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%, p < 0.001). OA patients had higher Sequential Organ Failure Assessment (4.7 vs 1.8, p < 0.001), American Society of Anesthesiologists Physical Status (3.6 vs 2.7, p < 0.001), and APACHE II scores (16.1 vs 9.4, p < 0.001). The mean duration of antibiotics was 6.5 days (8.0 OA vs 5.4 CA, p < 0.001). A total of 179 (23.8%) patients developed SI (33.1% OA vs 16.8% CA, p < 0.001). 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% (p < 0.001). CONCLUSIONS: 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.

The Obesity Paradox in Emergency General Surgery Patients.

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.

Laparoscopy is associated with decreased all-cause mortality in patients undergoing emergency general surgery procedures in a regional health system.

BACKGROUND: 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. METHODS: 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. RESULTS: 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/m2 vs. 28.8 ± 8.3, p < 0.001). Patients in the laparoscopic group had lower mean CCI score (1.6 ± 2.3 vs. 3.4 ± 3.2, p ≤ 0.0001). On multivariable analysis, open surgery had the highest association with inpatient mortality (OR 8.67, 4.23-17.75, p < 0.0001) and at all time points (30-, 90-day, 1-, 3-year). At all time points, conversion to open was found to be a statistically significant protective factor. CONCLUSION: Use 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.

Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Background: Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). Objective: The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU). Methods: A retrospective cohort study was conducted including subjects admitted to the intensive care unit (ICU), with suspected pneumonia, and negative BALCx. Data were compared based on length of exposure to antibiotics, PAU (antibiotics >4 days) versus nPAU (antibiotics <4 days). Results: A total of 128 subjects were included, 57 in the PAU group and 71 in the nPAU group. Baseline demographics were similar between groups. Severity of illness measured by multiple organ dysfunction scores at time of bronchoalveolar lavage (BAL) collection to final result showed a statistically significant decrease in the PAU group but not in the nPAU group. No differences were found in ICU days, ventilator-free days, or mortality; however, length of stay was longer for PAU (23 vs. 17, p = .04). In the PAU group, there were fewer BALCx results of "no growth" (23% vs. 45%, p = .04), more positive gram stains (83% vs. 60%, p = .01) and more positive non-BALCx (40% vs. 14%, p = .01). In a multivariate analysis, factors associated with PAU were positive BAL gram stains (adjusted odds ratio [aOR] 3.1, p = .037) and positive non-BALCx (aOR 4.7, p = .002). Conclusion: For subjects with suspected pneumonia and negative BALCx, positive non-BALCx and positive BALCx gram stain influenced the length of exposure of antibiotics.

Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study.

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.

Readmission After Emergency General Surgery: NSQIP Review of Risk, Cause and Ideal Follow-Up.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 LOS >2 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 occur <10 d after discharge. CONCLUSIONS: 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.

Antibiotic Exposure Is Not Associated With Clearance of Bronchoalveolar Growth: Results From a Prospective Ventilator-Associated Pneumonia Study.

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.

Estimating the Impact of Necrotizing Soft Tissue Infections in the United States: Incidence and Re-Admissions.

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 hospital mortality after NSTI have increased the number of survivors at risk for long-term sequelae. This study estimates the incidence of NSTI and the burden of re-admission and associated healthcare spending in patients who survived admission for NSTI. Methods: Index admissions for NSTI were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes combined with either Current Procedural Technology (CPT) or diagnosis-related group codes to increase specificity. Two separate datasets were used to provide primary and secondary estimates of the annual incidence of NSTIs in the United States: the National Inpatient Sample (NIS) for the years 2012-2016 and the Watson Health dataset for 2009-2013, respectively, and extrapolated to estimate the incidence for 2018. The Nationwide Readmissions Database (NRD) from 2013-2015 was used to estimate of the risk for re-admission, cost of re-admissions, and to compare 90-day re-admission rates for NSTI to common medical conditions. Results: National Inpatient Sample and Watson Health datasets demonstrated an increasing annual incidence and estimated 33,600 and 28,500 cases in 2018, respectively. The estimated annual incidences in the United States in 2018 were 10.3 and 8.7 per 100,000 persons, respectively. Risk of 90-day re-admission ranged from 24%-29% over the 3 years, 89% of which were unplanned. Of those re-admitted, 90% had one or more comorbidities, the most common diagnoses associated with re-admission were infection in 65%, acute kidney injury in 22%, and shock in 10%. The median re-admission length of stay was seven days (interquartile range [IQR]: 4-13 days) with a median cost of re-admission of $13,590 (IQR: $7186-$27440). Conclusion: The incidence of NSTI is more common than generally reported. Re-admission within 90 days is common, occurring in more than one in four survivors resulting in high healthcare costs.

The CELIOtomy Risk Score: An effort to minimize futile surgery with analysis of early postoperative mortality after emergency laparotomy.

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.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.

Pro-Con Perspectives on Ethics in Surgical Research: Update from the 39th Annual Surgical Infection Society Meeting.

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.

Surgical Infection Society Guidance for Operative and Peri-Operative Care of Adult Patients Infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.

Maximizing the Calm before the Storm: Tiered Surgical Response Plan for Novel Coronavirus (COVID-19).

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.

Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.

BACKGROUND: Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE: Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS: Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS: eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION: Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.