Search

Kaushik Mukherjee,1 Vance L Albaugh,2 Justin E Richards,3 Kelli A Rumbaugh,4 Addison K May1 1Division of Trauma and Surgical Critical Care, 2Division of General Surgery, 3Department of Anesthesiology, 4Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Glucose metabolism in humans is exceedingly complex. At baseline, it is controlled by elaborate signaling mechanisms, and these mechanisms are profoundly altered by the surge of catecholamines and cytokines associated with acute postsurgical and post-traumatic stress. These alterations in signaling mechanisms result in hyperglycemia; although this hyperglycemia can start very rapidly after the traumatic or surgical insult, it can persist during the entire period of critical illness and even afterward. Numerous randomized clinical trials have been conducted to determine if hyperglycemia is associated with increased mortality in surgical patients. These studies have had different conclusions that are difficult to interpret in light of differences in study methodology, but there is certainly ample evidence that inadequately controlled hyperglycemia causes harm due to increased infectious morbidity, and possibly increased mortality. As we have become more proficient in controlling hyperglycemia, the concept of insulin resistance, determined as the amount of insulin required to achieve hyperglycemia, has come to the fore. Insulin resistance is not a static concept, and may change before significant events such as infection. Patients with elevated and persistent insulin resistance have been demonstrated to suffer increased infectious morbidity and mortality, albeit in nonrandomized studies. Along with insulin resistance, the concept of glycemic variability, the amount of variation in serum blood glucose over time, has also become relevant; increased variability has been associated with hypoglycemia and mortality. Both of these risks can result from aggressive insulin therapy, and glycemic control protocols must be appropriately planned and implemented to avoid hypoglycemia and excessive externally induced variability. Computer-assisted protocols may be of significant benefit in optimizing glycemic control. The most recent recommendations available are to keep serum blood glucose levels below 150 mg/dL and to avoid hypoglycemia. Keywords: insulin resistance, hypoglycemia, insulin signaling, hyperglycemia, critical illness, glycemic variability

Background:The Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (e.g. non-pulmonary sepsis); however, this hypothesis has not been well-studied in humans. Methods:We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single center study of 100 patients with ARDS and severe sepsis, and in a secondary analysis of 853 ARDS patients drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. Results:In both studies, direct ARDS patients had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein-D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2), compared with indirect ARDS patients. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, direct ARDS patients also had lower levels of von Willebrand factor antigen and interleukins 6 and 8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Conclusions:Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct or indirect ARDS, respectively.The Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (e.g. non-pulmonary sepsis); however, this hypothesis has not been well-studied in humans.We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single center study of 100 patients with ARDS and severe sepsis, and in a secondary analysis of 853 ARDS patients drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts.In both studies, direct ARDS patients had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein-D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2), compared with indirect ARDS patients. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, direct ARDS patients also had lower levels of von Willebrand factor antigen and interleukins 6 and 8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS.Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct or indirect ARDS, respectively.

Background: The Lung Injury Score (LIS) remains a commonly utilized measure of lung injury severity though the additive value of LIS to predict ARDS outcomes over the recent Berlin definition of ARDS, which incorporates severity, is not known. Methods: We

Introduction: Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker pane

ازداد في الآونة الأخيرة الاتجاه نحو استخدام اللعاب كبديل عن المصل في تشخيص العديد من الحالات في طب الأسنان , وكذلك الاهتمام بالأنزيمات والبحث عن وجود علاقة بين مستويات الأنزيمات والمعالجات المختلفة.وباعتبار الفوسفات القلوي من المحددات الأساسية لإعادة تشكيل العظام توجهالاهتمام بالبحث عن علاقة لاختلاف تركيز اللعاب لهذا الانزيم وربطها بالحركة السنية التقويمية . هدف الدراسة: تقييم مستويات أنزيم الأكالين فوسفات(Alp) في اللعاب عند المرضى المعالجون بأجهزة تقويمية ثابتة في مرحلة رصف وتسوية الأسنان. المواد والطرق: تضمنت عينة الدراسة( 9) مرضى من مراجعين قسم تقويم الأسنان والفكين وهم بحاجة لمعالجة بجهاز تقويمي ثابت، تم أخذ عينة من اللعاب من خلال محقنة بلاستيكية نبوذة( 3مل ) قبل العمل وبعد تركيب الجهاز وبعد عدة فترات أخرى ومعايرة اللعاب ضمن جهاز مقياس الطيف الضوئي . النتائج: كان هناك ارتفاع بمستوى الأنزيم بعد 7 أيام من العمل و بعد 14 يوم وكان هذا الارتفاع هام احصائيا.في حين لم يكن هناك أي تغيرات خلال الساعة الأولى و اليوم الأول. الاستنتاجات: يمكن استخدام الألكالين فوسفات (Alp)كمؤشر حيوي في اللعاب.

Background: The hyperglycemic state following trauma and surgery is related partially to insulin resistance (IR). The objective is to determine if critically ill surgical patients vary in their extent of IR and is IR associated with mortality. Methods: Prospective observational study in trauma and surgical intensive care units. There were 925 ventilated, critically ill surgical patients who were placed on an automated euglycemia protocol. A mathematic multiplier (M) employed by the protocol was used as a measure of IR. Outcome, phenotypic, laboratory, and treatment variables were analyzed. Results: 54,141 entries for glucose (mg/dl) and M were analyzed. Median glucose was 118mg/dL, with 45% of values between 80-110mg/dL, 81% between 80-150 mg/dL, and 0.2% less than 40 mg/ dL. M varied by 42 fold over the entire population, and by an average of 11-fold among individual patients. The median blood glucose was not different between groups (118 mg/dl for survivors and 118 mg/dl for non-survivors, P = 0.36). The median insulin dose and M were significantly higher in non-survivors (4.1 U/hr versus 3.4 U/hr, P = 0.005; 0.061 versus 0.058, P = 0.02). Conclusions: There was a large amount of variation in insulin resistance, as measured by an adapting multiplier, both across the population and within patients. In the setting of tight glucose control measures of glucose control (median blood glucose and percent in range) do not differentiate between patients who lived and died while measures of insulin resistance (median insulin dose and multiplier) do, suggesting that the insulin resistance is a better predictor of outcome. [ABSTRACT FROM AUTHOR]

Objective: Sexual dimorphism (variation in outcome related to sex) after trauma-hemorrhage and sepsis is well documented in animals, with the pro-estrus state being proinflammatory and associated with a survival advantage. Although some observational studies confirm this pattern in humans, others demonstrate no difference in mortality. Estrogens are important modulators of the inflammatory response and insulin resistance in humans and have been linked to increased mortality during sepsis. Our objective was to determine whether sex hormone levels were associated with outcomes in critically ill surgical patients.Design: Prospective cohort.Patients: A total of 301 adult critically ill or injured surgical patients remaining in the intensive care unit for > or = 48 hrs at two academic medical centers.Interventions: None.Measurements: Blood was collected 48 hrs after intensive care unit admission and assayed for sex hormones (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor necrosis factor-alpha and interleukin-1, -2, -4, -6, -8, and -10). Demographic and outcome data were also collected.Main Results: Estradiol was significantly higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol demonstrated greater than a three-fold increase in the mortality rate for the highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with an odds ratio for death of 4.60 (95% confidence interval, 1.56-13.0) compared with a reference estradiol level of 45 pg/mL.Conclusions: We conclude that serum estradiol correlates with mortality in critically ill and injured surgical patients and discuss potential mechanisms for this observation. [ABSTRACT FROM AUTHOR]

Objective: Hyperglycemia worsens clinical outcomes in critically ill patients. Precise glycemia control using intravenous insulin improves outcomes. To determine if we could improve glycemia control over a previous paper-based, manual protocol, authors implemented, in a surgical intensive care unit (SICU), an intravenous insulin protocol integrated into a care provider order entry (CPOE) system.Design: Retrospective before-after study of consecutive adult patients admitted to a SICU during pre (manual protocol, 32 days) and post (computer-based protocol, 49 days) periods.Measurements: Percentage of glucose readings in ideal range of 70-109 mg/dl, and minutes spent in ideal range of control during the first 5 days of SICU stay.Results: The computer-based protocol reduced time from first glucose measurement to initiation of insulin protocol, improved the percentage of all SICU glucose readings in the ideal range, and improved control in patients on IV insulin for > or =24 hours. Hypoglycemia (<40 mg/dl) was rare in both groups.Conclusion: The CPOE-based intravenous insulin protocol improved glycemia control in SICU patients compared to a previous manual protocol, and reduced time to insulin therapy initiation. Integrating a computer-based insulin protocol into a CPOE system achieved efficient, safe, and effective glycemia control in SICU patients. [ABSTRACT FROM AUTHOR]

Objectives: Acute Care Surgery (ACS) admissions and procedures are substantially increasing. ACS disproportionally accounts for a majority of morbidity and mortality among surgical patients. Minimally invasive techniques are associated with improved outcomes and shorter hospital length of stay within the ACS population. While laparoscopy is widespread, ACS surgeons have been slower to adopt the use of robotics. We aimed to evaluate the feasibility of incorporating robotic surgery within ACS practice., Methods: Robotic General Surgery operations performed by 8 Acute Care Surgeons from 5 local facilities within a large integrated healthcare system were queried over a 15 month period. Patients who underwent emergent, urgent, sub-acute, and elective robotic operations by ACS staff were identified. Demographics collected included age, gender, BMI, and ASA score. Outcomes recorded included procedure classification, total supply and implant charges (TSI), conversion to open, hospital length of stay (LOS), 30 day readmission, and 30 day mortality., Results: Of 200 operations, the most common were Cholecystectomy (43.5%), Inguinal hernia repair (26.0%), Ventral hernia repair (18.0%), Appendectomy (5.0%), and Sigmoid Colectomy (3.5%). The median (± std dev) age was 48 ± 16.66 years and BMI was 29.9 ± 8.79 kg/m 2 . 46% of cases were sub-acute (n = 92), 33.5% were elective (n = 67), 14% were emergent (n = 28), and 6.5% were urgent (n = 13). Most patients were ASA 2 (107, 46.1%) or ASA 3 (71, 45.9%). The median (IQR) TSI and LOS were $1,770 (889.50) USD and 0.1 (0.9) days. Forty-one inpatient procedures were performed. Median LOS was 3 days and expected LOS was 3.1 days (O:E = 0.96). Five patients were readmitted within 30 days, and there were no deaths within 30 days., Conclusion: Robotic techniques may be safely implemented by ACS surgeons, potentially benefitting both patient and surgeon. LOS was similar between laparoscopic and robotic cases and only two cases required conversion to an open procedure. Next steps include a multi-center prospective trial comparing robotic to laparoscopic cases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data. Child-caregiver dyads were recruited from informal tented settlements in Lebanon, and completed a battery of psychological instruments at baseline and follow-up (12 months apart). Univariate and multivariate Bayesian linear mixed models were used to examine a) the interrelationships between markers of sensitivity and b) the ability of sensitivity markers to predict anxiety, depression, post-traumatic stress disorder, and externalising behaviour. Self-reported sensitivity (using the Highly Sensitive Child Scale) significantly predicted a higher burden of all forms of mental illness across both waves, however, there were no significant cross-lagged pathways. Physiological and genetic markers were not stably predictive of self-reported sensitivity, and failed to similarly predict mental health outcomes. The measurement of environmental sensitivity may have significant implications for identifying and treating mental illness, especially amongst vulnerable populations, but clinical utility is currently limited to self-report assessment., (© 2024. The Author(s).)

For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees' mental health. As a relatively new research method, however, there remain several complexities and uncertainties surrounding the use of hair hormones, from initial hair sampling to final statistical analysis, many of which are underappreciated in the extant literature, and restrict the potential utility of hair hormones. To promote awareness, we provide a narrative overview of our experiences collecting and analyzing hair hormone data in a large cohort of Syrian refugee children ( n  = 1594), across two sampling waves spaced 12 months apart. We highlight both the challenges faced, and the promising results obtained thus far, and draw comparisons to other prominent studies in this field. Recommendations are provided to future researchers, with emphasis on longitudinal study designs, thorough collection and reporting of hair-related variables, and careful adherence to current laboratory guidelines and practices., Competing Interests: No conflict of interest., (© 2024 The Authors.)

Refugee children are often exposed to substantial trauma, placing them at increased risk for mental illness. However, this risk can be mitigated by a capacity for resilience, conferred from multiple ecological systems (e.g., family, community), including at an individual biological level. We examined the ability of hair cortisol concentrations and polygenic scores for mental health to predict risk and resilience in a sample of Syrian refugee children ( n = 1359). Children were categorized as either at-risk or resilient depending on clinical thresholds for posttraumatic stress disorder, depression, and externalizing behavior problems. Logistic regression was used to examine main and interacting effects while controlling for covariates. Elevated hair cortisol concentrations were significantly associated with reduced resilience (odds ratio (OR)=0.58, 95%CI [0.40, 0.83]) while controlling for levels of war exposure. Polygenic scores for depression, self-harm, and neuroticism were not found to have any significant main effects. However, a significant interaction emerged between hair cortisol and polygenic scores for depression (OR=0.04, 95%CI [0.003 0.47]), suggesting that children predisposed to depression were more at risk for mental health problems when hair cortisol concentrations were high. Our results suggest that biomarkers (separately and in combination) might support early identification of refugee children at risk for mental health problems.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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.

Interactions between the MAOA uVNTR and rearing environment are suggested to influence the developmental manifestations of childhood internalizing and externalizing behavior. However, few studies in the MAOA literature have included continental African children, or focused on non-clinical samples. We explored the main and interactive effects of the MAOA uVNTR (high and low activity alleles) in Black South African male ( n  = 478) and female ( n  = 540) children who were part of the longitudinal Birth to Twenty Plus cohort. Historical data on birth weight, gestational age at delivery, socioeconomic status, and maternal education were combined with genotypic information and analyzed using regression modeling. We found no significant main effects for the MAOA uVNTR on childhood behavior in either sex. A significant interaction ( p = .04) was identified between MAOA and maternal education, suggesting that externalizing behavior in boys carrying a low activity MAOA allele varied in direct proportion to the education levels of their mothers. However, the model fit failed to reach significance, possibly due to our inclusion of only non-clinical pre-pubertal males. No significant interactions were detected for female children. Our findings lend tentative credibility to the Environmental Sensitivity metaframework, which suggests that MAOA is an important plasticity factor in childhood development.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The 2016 National Academies of Science, Engineering and Medicine report included a proposal to establish a National Trauma Research Action Plan. In response, the Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care from prehospital care to rehabilitation as part of an overall strategy to achieve zero preventable deaths and disability after injury. The Postadmission Critical Care Research panel was 1 of 11 panels constituted to develop this research agenda., Methods: We recruited interdisciplinary experts in surgical critical care and recruited them to identify current gaps in clinical critical care research, generate research questions, and establish the priority of these questions using a consensus-driven Delphi survey approach. The first of four survey rounds asked participants to generate key research questions. On subsequent rounds, we asked survey participants to rank the priority of each research question on a 9-point Likert scale, categorized to represent low-, medium-, and high-priority items. Consensus was defined as ≥60% of panelists agreeing on the priority category., Results: Twenty-five subject matter experts generated 595 questions. By Round 3, 249 questions reached ≥60% consensus. Of these, 22 questions were high, 185 were medium, and 42 were low priority. The clinical states of hypovolemic shock and delirium were most represented in the high-priority questions. Traumatic brain injury was the only specific injury pattern with a high-priority question., Conclusion: The National Trauma Research Action Plan critical care research panel identified 22 high-priority research questions, which, if answered, would reduce preventable death and disability after injury., Level of Evidence: Diagnostic Tests or Criteria; Level IV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Andrew K. May et al.)

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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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/m 2 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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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/m 2 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/m 2 , 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: 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., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Resistance-based blood flow restriction training (BFRT) improves skeletal muscle strength and size. Unlike heavy-load resistance training (HLRT), there is debate as to whether strength adaptations following BFRT interventions can be primarily attributed to concurrent muscle hypertrophy, as the magnitude of hypertrophy is often minor. The present study aimed to investigate the effect of 7 weeks of BFRT and HLRT on muscle strength and hypertrophy. The expression of protein growth markers from muscle biopsy samples was also measured. Male participants were allocated to moderately heavy-load training (HL; n  = 9), low-load BFRT (LL + BFR; n  = 8), or a control (CON; n  = 9) group to control for the effect of time. HL and LL + BFR completed 21 training sessions (3 d.week -1 ) comprising bilateral knee extension and knee flexion exercises (HL = 70% one-repetition maximum (1-RM), LL + BFR = 20% 1-RM + blood flow restriction). Bilateral knee extension and flexion 1-RM strength were assessed, and leg muscle CSA was measured via peripheral quantitative computed tomography. Protein growth markers were measured in vastus lateralis biopsy samples taken pre- and post the first and last training sessions. Biopsy samples were also taken from CON at the same time intervals as HL and LL + BFR. Knee extension 1-RM strength increased in HL (19%) and LL + BFR (19%) but not CON (2%; p  < 0.05). Knee flexion 1-RM strength increased similarly between all groups, as did muscle CSA (50% femur length; HL = 2.2%, LL + BFR = 3.0%, CON = 2.1%; TIME main effects). 4E-BP1 (Thr37/46) phosphorylation was lower in HL and LL + BFR immediately post-exercise compared with CON in both sessions ( p  < 0.05). Expression of other growth markers was similar between groups ( p  > 0.05). Overall, BFRT and HLRT improved muscle strength and size similarly, with comparable changes in intramuscular protein growth marker expression, both acutely and chronically, suggesting the activation of similar anabolic pathways. However, the low magnitude of muscle hypertrophy was not significantly different to the non-training control suggesting that strength adaptation following 7 weeks of BFRT is not driven by hypertrophy, but rather neurological adaptation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 May, Russell, Della Gatta and Warmington.)

Background: Interstitial 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., Methods: Eligible 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., Discussion: The 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 registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true., (© 2021. The Author(s).)

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

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: 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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)