Hospital Outcomes in Patients Who Developed Acute Respiratory Distress Syndrome After Community-Acquired Pneumonia.

Purpose: To identify risk factors for and outcomes in acute respiratory distress syndrome (ARDS) in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a retrospective study using the Premier Healthcare Database between 2016 and 2020. Patients diagnosed with pneumonia, requiring mechanical ventilation (MV), antimicrobial therapy, and hospital admission ≥2 days were included. Multivariable regression models were used for outcomes including in-hospital mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, and days on MV. Results: 1924 (2.7%) of 72 107 patients with CAP developed ARDS. ARDS was associated with higher mortality (33.7% vs 18.9%; adjusted odds ratio 2.4; 95% confidence interval [CI] 2.16-2.66), longer hospital LOS (13 vs 9 days; adjusted incidence risk ratio (aIRR) 1.24; 95% CI 1.20-1.27), ICU LOS (9 vs 5 days; aIRR 1.51; 95% CI 1.46-1.56), more MV days (8 vs 5; aIRR 1.54; 95% CI 1.48-1.59), and increased hospitalization cost ($46 459 vs $29 441; aIRR 1.50; 95% CI 1.45-1.55). Conclusion: In CAP, ARDS was associated with worse in-patient outcomes in terms of mortality, LOS, and hospitalization cost. Future studies are needed to explore outcomes in patients with CAP with ARDS and explore risk factors for development of ARDS after CAP.

Whole Blood Resuscitation for Injured Patients Requiring Transfusion: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma.

INTRODUCTION: Whole blood resuscitation has reemerged as a resuscitation strategy for injured patients. However, the effect of whole blood-based resuscitation on outcomes has not been established. The primary objective of this guideline was to develop evidence-based recommendations on whether whole blood should be considered in civilian trauma patients receiving blood transfusions. METHODS: An EAST working group performed a systematic review and meta-analysis utilizing the GRADE methodology. One PICO question was developed to analyze the effect of whole blood resuscitation in the acute phase on mortality, transfusion requirements, infectious complications, and ICU length of stay. English language studies including adult civilian trauma patients comparing in-hospital whole blood to component therapy were included. Medline, Embase, Cochrane CENTRAL, CINAHL Plus, and Web of Science were queried. GRADEpro was used to assess quality of evidence and risk of bias. The study was registered on PROSPERO (#CRD42023451143). RESULTS: A total of 21 studies were included. Most patients were severely injured and required blood transfusion, massive transfusion protocol activation, and/or a hemorrhage control procedure in the early phase of resuscitation. Mortality was assessed separately at the following intervals: early (i.e., ED, 3-, or 6-hour), 24-hour, late (i.e., 28- or 30-day), and in-hospital. On meta-analysis, whole blood was not associated with decreased mortality. Whole blood was associated with decreased 4-hour RBC (mean difference -1.82, 95% CI -3.12 to -0.52), 4-hour plasma (mean difference -1.47, 95% CI -2.94 to 0), and 24-hour RBC transfusions (mean difference -1.22, 95% CI -2.24 to -0.19) compared to component therapy. There were no differences in infectious complications or ICU length of stay between groups. CONCLUSION: We conditionally recommend WB resuscitation in adult civilian trauma patients receiving blood transfusions, recognizing that data are limited for certain populations, including women of childbearing age, and therefore this guideline may not apply to these populations. LEVEL OF EVIDENCE: Level III, Guidelines.

Fat malabsorption in critical illness.

Malnutrition in critical illness is common and is associated with significant increases in adverse outcomes. A hypermetabolic state and underfeeding both contribute to the incidence of malnutrition. Malabsorption caused by critical illness is also an important contributor to the development of malnutrition. The early provision of enteral nutrition is associated with improved outcomes. Strategies for nutrition therapy must be informed by the alterations in absorption of macronutrients present in these patients. The following review examines alterations in fat metabolism during critical illness, and its consequences to overall nutrition status. Critical illness, as well as the sequalae of common medical interventions, may lead to alterations in the mechanical and chemical processes by which fat is digested and absorbed. Mechanical alterations include delayed gastric emptying and changes to the normal gut transit time. Pharmacologic interventions aimed at reducing these impacts may themselves, negatively affect efficient fat absorption. Exocrine pancreatic insufficiency can also occur in critical illness and may be underappreciated as a cause of fat malabsorption. Dysfunction of the gut lymphatics has been proposed as a contributing factor to fat malabsorption, and additional work is needed to better describe and quantify those effects. Achieving optimal outcomes for nutrition therapy requires recognition of these alterations in fat digestion.

American Association for the Surgery of Trauma/American College of Surgeons Committee on Trauma clinical protocol for management of acute respiratory distress syndrome and severe hypoxemia.

LEVEL OF EVIDENCE: Therapeutic/Care Management: Level V.

Efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute pain after orthopedic trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Orthopedic Trauma Association.

Objectives: Fracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established. Methods: Clinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The working group reached consensus on the final evidence-based recommendations. Results: A total of 19 studies were identified for analysis. Not all outcomes identified as critically important were reported in all studies, and the outcome of pain control was too heterogenous to perform a meta-analysis. Nine studies reported on non-union (three randomized control trials), six of which reported no association with NSAIDs. The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively. Of studies reporting on pain control and reduction of opioids, the use of NSAIDs reduced pain and the need for opioids after traumatic fracture. One study reported on the outcome of acute kidney injury and found no association with NSAID use. Conclusions: In patients with traumatic fractures, NSAIDs appear to reduce post-trauma pain, reduce the need for opioids and have a small effect on non-union. We conditionally recommend the use of NSAIDs in patients suffering from traumatic fractures as the benefit appears to outweigh the small potential risks.

Non-surgical management and analgesia strategies for older adults with multiple rib fractures: A systematic review, meta-analysis, and joint practice management guideline from the Eastern Association for the Surgery of Trauma and the Chest Wall Injury Society.

BACKGROUND: Chest wall injury in older adults is a significant cause of morbidity and mortality. Optimal nonsurgical management strategies for these patients have not been fully defined regarding level of care, incentive spirometry (IS), noninvasive positive pressure ventilation (NIPPV), and the use of ketamine, epidural, and other locoregional approaches to analgesia. METHODS: Relevant questions regarding older patients with significant chest wall injury with patient population(s), intervention(s), comparison(s), and appropriate selected outcomes were chosen. These focused on intensive care unit (ICU) admission, IS, NIPPV, and analgesia including ketamine, epidural analgesia, and locoregional nerve blocks. A systematic literature search and review were conducted, our data were analyzed qualitatively and quantitatively, and the quality of evidence was assessed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. No funding was used. RESULTS: Our literature review (PROSPERO 2020-CRD42020201241, MEDLINE, EMBASE, Cochrane, Web of Science, January 15, 2020) resulted in 151 studies. Intensive care unit admission was qualitatively not superior for any defined cohort other than by clinical assessment. Poor IS performance was associated with prolonged hospital length of stay, pulmonary complications, and unplanned ICU admission. Noninvasive positive pressure ventilation was associated with 85% reduction in odds of pneumonia ( p < 0.0001) and 81% reduction in odds of mortality ( p = 0.03) in suitable patients without risk of airway loss. Ketamine use demonstrated no significant reduction in pain score but a trend toward reduced opioid use. Epidural and other locoregional analgesia techniques did not affect pneumonia, length of mechanical ventilation, hospital length of stay, or mortality. CONCLUSION: We do not recommend for or against routine ICU admission. We recommend use of IS to inform ICU status and conditionally recommend use of NIPPV in patients without risk of airway loss. We offer no recommendation for or against ketamine, epidural, or other locoregional analgesia. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level IV.

Management of adult renal trauma: a practice management guideline from the eastern association for the surgery of trauma.

BACKGROUND: The kidney is the most frequently injured component of the genitourinary system, accounting for 5% of all trauma cases. Several guidelines by different societies address the management of urological trauma. However, unanswered questions remain regarding optimal use of angioembolization in hemodynamically stable patients, indications for operative exploration of stable retroperitoneal hematomas and renal salvage techniques in the setting of hemodynamic instability, and imaging practices for patients undergoing non-operative management. We performed a systematic review, meta-analysis, and developed evidence-based recommendations to answer these questions in both blunt and penetrating renal trauma. METHODS: The working group formulated four population, intervention, comparator, outcome (PICO) questions regarding the following topics: (1) angioembolization (AE) usage in hemodynamically stable patients with evidence of ongoing bleeding; (2) surgical approach to stable zone II hematomas (exploration vs. no exploration) in hemodynamically unstable patients and (3) surgical technique (nephrectomy vs. kidney preservation) for expanding zone II hematomas in hemodynamically unstable patients; (4) frequency of repeat imaging (routine or symptom based) in high-grade traumatic renal injuries. A systematic review and meta-analysis of currently available evidence was performed. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members and concurrence was obtained for each final recommendation. RESULTS: A total of 20 articles were identified and analyzed. Two prospective studies were encountered; the majority were retrospective, single-institution studies. Not all outcomes projected by PICO questions were reported in all studies. Meta-analysis was performed for all PICO questions except PICO 3 secondary to the discrepant patient populations included in those studies. PICO 1 had the greatest number of articles included in the meta-analysis with nine studies; yet, due to differences in study design, no critical outcomes emerged; similar differences among a smaller set of articles prevented observation of critical outcomes for PICO 4. Analyses of PICOs 2 and 3 favored a non-invasive or minimally invasive approach in-line with current international practice trends. CONCLUSION: In hemodynamically stable adult patients with clinical or radiographic evidence of ongoing bleeding, no recommendation could be made regarding the role of AE vs. observation. In hemodynamically unstable adult patients, we conditionally recommend no renal exploration vs. renal exploration in stable zone II hematomas. In hemodynamically unstable adult patients, we conditionally recommend kidney preserving techniques vs. nephrectomy in expanding zone II hematomas. No recommendation could be made for the optimal timing of repeat imaging in high grade renal injury. LEVEL OF EVIDENCE: Guideline; systematic review, level III.

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome coronavirus 2-induced hyperinflammation is one of the mechanisms underlying the high mortality, the association between age and innate immune responses in COVID-19 mortality remains unclear. DESIGN: Flow cytometry of fresh blood and multiplexed inflammatory chemokine measurements of sera were performed on samples collected longitudinally from our cohort. Aggregate impact of comorbid conditions was calculated with the Charlson Comorbidity Index, and association between patient factors and outcomes was calculated via Cox proportional hazard analysis and repeated measures analysis of variance. SETTING: A cohort of severely ill COVID-19 patients requiring ICU admission was followed prospectively. PATIENTS: In total, 67 patients (46 male, age 59 ± 14 yr) were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality in our cohort was 41.8%. We identified older age (hazard ratio [HR] 1.09 [95% CI 1.07-1.11]; p = 0.001), higher comorbidity index (HR 1.24 [95% CI 1.14-1.35]; p = 0.039), and hyponatremia (HR 0.90 [95% CI 0.82-0.99]; p = 0.026) to each independently increase risk for death in COVID-19. We also found that neutrophilia (R = 0.2; p = 0.017), chemokine C-C motif ligand (CCL) 2 (R = 0.3; p = 0.043), and C-X-C motif chemokine ligand 9 (CXCL9) (R = 0.3; p = 0.050) were weakly but significantly correlated with mortality. Older age was associated with lower monocyte (R = -0.2; p = 0.006) and cluster of differentiation (CD) 16+ cell counts (R = -0.2; p = 0.002) and increased CCL11 concentration (R = 0.3; p = 0.050). Similarly, younger patients (< 65 yr) demonstrated a rise in CD4 (b-coefficient = 0.02; p = 0.036) and CD8 (0.01; p = 0.001) counts, as well as CCL20 (b-coefficient = 6.8; p = 0.036) during their ICU stay. This CD8 count rise was also associated with survival (b-coefficient = 0.01; p = 0.023). CONCLUSIONS: Age, comorbidities, and hyponatremia independently predict mortality in severe COVID-19. Neutrophilia and higher CCL2 and CXCL9 levels are also associated with higher mortality, while independent of age.

Ketamine in Critically Ill Patients: Use, Perceptions, and Potential Barriers.

Objective: To evaluate practitioner use of ketamine and identify potential barriers to use in acutely and critically ill patients. To compare characteristics, beliefs, and practices of ketamine frequent users and non-users. Methods: An online survey developed by members of the Society of Critical Care Medicine (SCCM) Clinical Pharmacy and Pharmacology Section was distributed to physician, pharmacist, nurse practitioner, physician assistant and nurse members of SCCM. The online survey queried SCCM members on self-reported practices regarding ketamine use and potential barriers in acute and critically ill patients. Results: Respondents, 341 analyzed, were mostly adult physicians, practicing in the United States at academic medical centers. Clinicians were comfortable or very comfortable using ketamine to facilitate intubation (80.0%), for analgesia (77.9%), procedural sedation (79.4%), continuous ICU sedation (65.8%), dressing changes (62.4%), or for asthma exacerbation and status epilepticus (58.8% and 40.4%). Clinicians were least comfortable with ketamine use for alcohol withdrawal and opioid detoxification (24.7% and 23.2%). Most respondents reported "never" or "infrequently" using ketamine preferentially for continuous IV analgesia (55.6%) or sedation (61%). Responses were mixed across dosing ranges and duration. The most common barriers to ketamine use were adverse effects (42.6%), other practitioners not routinely using the medication (41.5%), lack of evidence (33.5%), lack of familiarity (33.1%), and hospital/institutional policy guiding the indication for use (32.3%). Conclusion: Although most critical care practitioners report feeling comfortable using ketamine, there are many inconsistencies in practice regarding dose, duration, and reasons to avoid or limit ketamine use. Further educational tools may be targeted at practitioners to improve appropriate ketamine use.

Antibiotic prophylaxis for tube thoracostomy placement in trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma.

Background: Antibiotic prophylaxis is routinely administered for most operative procedures, but their utility for certain bedside procedures remains controversial. We performed a systematic review and meta-analysis and developed evidence-based recommendations on whether trauma patients receiving tube thoracostomy (TT) for traumatic hemothorax or pneumothorax should receive antibiotic prophylaxis. Methods: Published literature was searched through MEDLINE (via PubMed), Embase (via Elsevier), Cochrane Central Register of Controlled Trials (via Wiley), Web of Science and ClinicalTrials.gov databases by a professional librarian. The date ranges for our literature search were January 1900 to March 2020. A systematic review and meta-analysis of currently available evidence were performed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Results: Fourteen relevant studies were identified and analyzed. All but one were prospective, with eight being prospective randomized control studies. Antibiotic prophylaxis protocols ranged from a single dose at insertion to 48 hours post-TT removal. The pooled data showed that patients who received antibiotic prophylaxis were significantly less likely to develop empyema (OR 0.47, 95% CI 0.25 to 0.86, p=0.01). The benefit was greater in patients with penetrating injuries (penetrating OR 0.25, 95% CI 0.10 to 0.59, p=0.002, vs blunt OR 0.25, 95% CI 0.06 to 1.12, p=0.07). Administration of antibiotic prophylaxis did not significantly affect pneumonia incidence or mortality. Discussion: In adult trauma patients who require TT insertion, we conditionally recommend antibiotic prophylaxis be given at the time of insertion to reduce incidence of empyema. PROSPERO registration number: CRD42018088759.

Vaccination after spleen embolization: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Angioembolization is an important adjunct in the non-operative management of adult trauma patients with splenic injury. Multiple studies have shown that angioembolization may increase the non-operative splenic salvage rate for patients with high-grade splenic injuries. We performed a systematic review and developed evidence-based recommendations regarding the need for post-splenectomy vaccinations after splenic embolization in trauma patients. METHODS: A systematic review and meta-analysis of currently available evidence were performed utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Nine studies were identified and analyzed. A total of 240 embolization patients were compared to 443 control patients who neither underwent splenectomy nor were embolized. There was no statistical difference between the splenic immune function of embolized and control patients. In addition, a total of 3974 splenectomy patients was compared with 686 embolization patients. Embolization patients had fewer infectious complications and a greater degree of preserved splenic immune function. CONCLUSION: In adult trauma patients who have undergone splenic angioembolization, we conditionally recommend against routine post-splenectomy vaccinations. STUDY TYPE: systematic review/meta-analysis Level of evidence: level III.

Management of the open abdomen: A systematic review with meta-analysis and practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Multiple techniques describe the management of the open abdomen (OA) and restoration of abdominal wall integrity after damage-control laparotomy (DCL). It is unclear which operative technique provides the best method of achieving primary myofascial closure at the index hospitalization. METHODS: A writing group from the Eastern Association for the Surgery of Trauma performed a systematic review and meta-analysis of the current literature regarding OA management strategies in the adult population after DCL. The group sought to understand if fascial traction techniques or techniques to reduce visceral edema improved the outcomes in these patients. The Grading of Recommendations Assessment, Development and Evaluation methodology was utilized, meta-analyses were performed, and an evidence profile was generated. RESULTS: Nineteen studies met inclusion criteria. Overall, the use of fascial traction techniques was associated with improved primary myofascial closure during the index admission (relative risk, 0.32) and fewer hernias (relative risk, 0.11.) The use of fascial traction techniques did not increase the risk of enterocutaneous fistula formation nor mortality. Techniques to reduce visceral edema may improve the rate of closure; however, these studies were very limited and suffered significant heterogeneity. CONCLUSION: We conditionally recommend the use of a fascial traction system over routine care when treating a patient with an OA after DCL. This recommendation is based on the benefit of improved primary myofascial closure without worsening mortality or enterocutaneous fistula formation. We are unable to make any recommendations regarding techniques to reduce visceral edema. LEVEL OF EVIDENCE: Systematic Review and Meta-Analysis; Level IV.

Bovine versus porcine acellular dermal matrix for abdominal wall herniorrhaphy or bridging.

BACKGROUND: The management of complicated ventral hernias (CVH), namely ventral hernias in actively or recently infected/contaminated operative fields, and open abdomens in which the native fascia cannot be primarily reapproximated, pose a surgical challenge. Fetal Bovine and Porcine Acellular Dermal Matrix (BADM and PADM) biologic meshes are being increasingly used in these scenarios. A comparison, however, of clinically relevant outcomes between the two is lacking. With this investigation, we aim to review and compare clinically relevant outcomes in patients that underwent abdominal wall herniorrhaphy with either BADM or PADM at a tertiary urban academic institution over a 5-year period. METHODS: Patients who had a BADM or PADM implanted during CVH over a 5-year period at a tertiary urban academic hospital were identified. Baseline clinical and hernia characteristics, as well as postoperative outcomes were compared after a retrospective chart review. Phone interviews were also conducted to assess for recurrence, followed by in-person visits as indicated. Cox Proportional Hazard regression was fitted to identify risk factors for recurrence. RESULTS: Of the 140 patients who underwent biologic mesh implantation for CVH, 109 were for ventral hernia repair and 31 for open abdomen bridging. Mean age was 52.7 ± 14.2 and males constituted 57.9% of our sample, while 25.1% had undergone > 5 prior abdominal operations. Thirty percent were active smokers, and another 30% required emergency surgery. Only immunosuppression was a risk factor for recurrence [HR 13.3 (1.04-169.2), p = 0.047] on Cox Proportional Hazard regression, while mesh selection had no effect. CONCLUSIONS: Both BADM and PADM meshes perform well in CVH, with satisfactory recurrence rates, only slightly higher compared to traditional synthetic mesh repairs.

Management of rhabdomyolysis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: The treatment of rhabdomyolysis remains controversial. Although there is no question that any associated compartment syndrome needs to be identified and released, debate persists regarding the benefit of further therapy including aggressive intravenous fluid resuscitation (IVFR), urine alkalization with bicarbonate, and the use of mannitol. The goal of this practice management guideline was to evaluate the effects of bicarbonate, mannitol, and aggressive intravenous fluids on patients with rhabdomyolysis. METHODS: A systematic review and meta-analysis comparing treatments in patients with rhabdomyolysis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of evidence and to create evidence-based recommendations regarding the use of bicarbonate, mannitol, and aggressive IVFR in patients with rhabdomyolysis. RESULTS: A total of 12 studies were identified for analysis. On quantitative analysis, IVFR decreased the incidence of acute renal failure (ARF) and need for dialysis in patients with rhabdomyolysis. Neither bicarbonate nor mannitol administration improved the incidence of acute renal failure and need for dialysis in patients with rhabdomyolysis. Quality of evidence was deemed to be very low, with the vast majority of the literature being retrospective studies. CONCLUSION: In patients with rhabdomyolysis, we conditionally recommend for aggressive IVFR to improve outcomes of ARF and lessen the need for dialysis. We conditionally recommend against treatment with bicarbonate or mannitol in patients with rhabdomyolysis.

Acute Respiratory Distress Syndrome (ARDS) after trauma: Improving incidence, but increasing mortality.

PURPOSE: Acute Respiratory Distress Syndrome (ARDS) is an infrequent, yet morbid inflammatory complication in injury victims. With the current project we sought to estimate trends in incidence, determine outcomes, and identify risk factors for ARDS and related mortality. MATERIALS & METHODS: The national Trauma Quality Improvement Program dataset (2010-2014) was queried. Demographics, injury characteristics and outcomes were compared between patients who developed ARDS and those who did not. Logistic regression models were fitted for the development of ARDS and mortality respectively, adjusting for relevant confounders. RESULTS: In the studied 808,195 TQIP patients, incidence of ARDS decreased over the study years (3-1.1%, p < 0.001), but related mortality increased (18.-21%, p = 0.001). ARDS patients spent an additional 14.7 ± 10.3 days in the hospital, 9.7 ± 7.9 in the ICU, and 6.6 ± 9.4 on mechanical ventilation (all p < 0.001). Older age, male gender, African American race increased risk for ARDS. Age, male gender, lower GCS and higher ISS also increased mortality risk among ARDS patients. Several pre-existing comorbidities including chronic alcohol use, diabetes, smoking, and respiratory disease also increased risk. CONCLUSION: Although the incidence of ARDS after trauma appears to be declining, mortality is on the rise.

Sex differences in long-term outcomes after traumatic injury: A mediation analysis.

BACKGROUND: We sought to examine the association and potential mediators between sex and long-term trauma outcomes. METHODS: Moderately-to-severely injured patients admitted to 3 level-1 trauma centers were contacted between 6 and 12-months post-injury to assess for functional limitations, use of pain medications, and posttraumatic stress disorder (PTSD). Multivariable adjusted regression analyses were used to compare long-term outcomes by sex. Potential mediators of the relationship between sex and outcomes was explored using mediation analysis. RESULTS: 2607 patients were followed, of which 45% were female. Compared to male, female patients were more likely to have functional limitations (OR: 1.45; 95% CI: 1.31-1.60), take pain medications (OR: 1.17; 95% CI: 1.02-1.38), and screen positive for PTSD (OR: 1.60; 95% CI: 1.46-1.76) post-injury. Age, extremity injury, previous psychiatric illness, and pre-injury unemployment, partially mediated the effect of female sex on long-term outcomes. CONCLUSIONS: There are significant sex differences in long-term trauma outcomes, which are partially driven by patient and injury-related factors.

IL-10 and class 1 histone deacetylases act synergistically and independently on the secretion of proinflammatory mediators in alveolar macrophages.

INTRODUCTION: Anti-inflammatory cytokine IL-10 suppresses pro-inflammatory IL-12b expression after Lipopolysaccharide (LPS) stimulation in colonic macrophages, as part of the innate immunity Toll-Like Receptor (TLR)-NF-κB activation system. This homeostatic mechanism limits excess inflammation in the intestinal mucosa, as it constantly interacts with the gut flora. This effect is reversed with Histone Deacetylase 3 (HDAC3), a class I HDAC, siRNA, suggesting it is mediated through HDAC3. Given alveolar macrophages' prominent role in Acute Lung Injury (ALI), we aim to determine whether a similar regulatory mechanism exists in the typically sterile pulmonary microenvironment. METHODS: Levels of mRNA and protein for IL-10, and IL-12b were determined by qPCR and ELISA/Western Blot respectively in naïve and LPS-stimulated alveolar macrophages. Expression of the NF-κB intermediaries was also similarly assessed. Experiments were repeated with AS101 (an IL-10 protein synthesis inhibitor), MS-275 (a selective class 1 HDAC inhibitor), or both. RESULTS: LPS stimulation upregulated all proinflammatory mediators assayed in this study. In the presence of LPS, inhibition of IL-10 and/or class 1 HDACs resulted in both synergistic and independent effects on these signaling molecules. Quantitative reverse-transcriptase PCR on key components of the TLR4 signaling cascade demonstrated significant diversity in IL-10 and related gene expression in the presence of LPS. Inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the transcription of MyD88, IRAK1, Rela and the NF-κB p50 subunit. Interestingly, by quantitative ELISA inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the secretion of not only IL-10, IL-12b, and TNFα, but also proinflammatory mediators CXCL2, IL-6, and MIF. These results suggest that IL-10 and class 1 HDAC activity regulate both independent and synergistic mechanisms of proinflammatory cytokine/chemokine signaling. CONCLUSIONS: Alveolar macrophages after inflammatory stimulation upregulate both IL-10 and IL-12b production, in a highly class 1 HDAC-dependent manner. Class 1 HDACs appear to help maintain the balance between the pro- and anti-inflammatory IL-12b and IL-10 respectively. Class 1 HDACs may be considered as targets for the macrophage-initiated pulmonary inflammation in ALI in a preclinical setting.

Management of simple and retained hemothorax: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Traumatic hemothorax poses diagnostic and therapeutic challenges both acutely and chronically. A working group of the Eastern Association for the Surgery of Trauma convened to formulate a practice management guideline for traumatic hemothorax. METHODS: We formulated four questions: whether tube thoracostomy vs observation be performed, should pigtail catheter versus thoracostomy tube be placed to drain hemothorax, should thrombolytic therapy be attempted versus immediate thoracoscopic assisted drainage (VATS) in retained hemothorax (rHTX), and should early VATS (≤4 days) versus late VATS (>4 days) be performed? A systematic review was undertaken from articles identified in multiple databases. RESULTS: A total of 6391 articles were identified, 14 were selected for guideline construction. Most articles were retrospective with very low-quality evidence. We performed meta-analysis for some of the outcomes for three of the questions. CONCLUSIONS: For traumatic hemothorax we conditionally recommend pigtail catheters, in hemodynamically stable patients. In patients with rHTX, we conditionally recommend VATS rather than attempting thrombolytic therapy and recommend that it should be performed early (≤4 days).