Duration of antimicrobial treatment for complicated intra-abdominal infections after definitive source control: A systematic review, meta-analysis, and practice management guideline from the Eastern Association for the Surgery of Trauma

Recent studies have evaluated outcomes associated with duration of antimicrobial treatment for complicated intra-abdominal infections (cIAI). The goal of this guideline was to help clinicians better define appropriate antimicrobial duration in patients who have undergone definitive source control for cIAI. A working group of Eastern Association for the Surgery of Trauma (EAST) performed a systematic review and meta-analyses of the available data pertaining to the duration of antibiotics after definitive source control of cIAI in adult patients. Only studies that compared patients treated with short vs. long duration antibiotic regimens were included. The critical outcomes of interest were selected by the group. Noninferiority of short compared with long duration of antimicrobial treatment was defined as an indicator for a potential recommendation in favor of shorter antibiotics course. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of the evidence and to formulate recommendations. Sixteen studies were included. The short duration ranged from 1 dose to ≤10 days, with an average of 4 days, and the long duration ranged >1 day to 28 days, with an average of 8 days. There were no differences between short and long duration of antibiotics in terms of mortality (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.44), rate of surgical site infection (OR, 0.88; 95% CI, 0.56-1.38); persistent/recurrent abscess (OR, 0.76; 95% CI, 0.45-1.29); unplanned interventions (OR, 0.53; 95% CI, 0.12-2.26); hospital length of stay (mean difference, -2.62 days; CI, -7.08 to 1.83 days); or readmissions (OR, 0.92; 95% CI, 0.50-1.69). The level of evidence was assessed as very low. The group made a recommendation for shorter (four or less days) versus longer duration (eight or more days) of antimicrobial treatment in adult patients with cIAIs who had definitive source control.

Duration of antimicrobial treatment for complicated intra-abdominal infections after definitive source control: A systematic review, meta-analysis, and practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Recent studies have evaluated outcomes associated with duration of antimicrobial treatment for complicated intra-abdominal infections (cIAI). The goal of this guideline was to help clinicians better define appropriate antimicrobial duration in patients who have undergone definitive source control for cIAI. METHODS: A working group of Eastern Association for the Surgery of Trauma (EAST) performed a systematic review and meta-analyses of the available data pertaining to the duration of antibiotics after definitive source control of cIAI in adult patients. Only studies that compared patients treated with short vs. long duration antibiotic regimens were included. The critical outcomes of interest were selected by the group. Noninferiority of short compared with long duration of antimicrobial treatment was defined as an indicator for a potential recommendation in favor of shorter antibiotics course. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of the evidence and to formulate recommendations. RESULTS: Sixteen studies were included. The short duration ranged from 1 dose to ≤10 days, with an average of 4 days, and the long duration ranged >1 day to 28 days, with an average of 8 days. There were no differences between short and long duration of antibiotics in terms of mortality (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.44), rate of surgical site infection (OR, 0.88; 95% CI, 0.56-1.38); persistent/recurrent abscess (OR, 0.76; 95% CI, 0.45-1.29); unplanned interventions (OR, 0.53; 95% CI, 0.12-2.26); hospital length of stay (mean difference, -2.62 days; CI, -7.08 to 1.83 days); or readmissions (OR, 0.92; 95% CI, 0.50-1.69). The level of evidence was assessed as very low. CONCLUSION: The group made a recommendation for shorter (four or less days) versus longer duration (eight or more days) of antimicrobial treatment in adult patients with cIAIs who had definitive source control. LEVEL OF EVIDENCE: Systematic Review and Meta-Analysis; Level III.

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.

Re-Admission in Patients with Necrotizing Soft Tissue Infections: Continuity of Care Matters.

Background: Necrotizing soft tissue infections (NSTIs) are rapidly progressive infections with high mortality and complication rates. The incidence of NSTIs has been increasing steadily whereas mortality has decreased; survivors have a high risk of re-hospitalization. We hypothesized that re-admission to the index hospital where the first admission occurred would be associated with better clinical outcomes compared with re-admission to a non-index hospital. Patients and Methods: We identified patients from the 2017 Nationwide Readmissions Database with an index admission for NSTIs and examined all-cause re-admissions within 90 days of discharge. We noted whether re-admission occurred at the index or a non-index hospital. Survey-weighted logistic regression identified factors associated with death at the first re-admission and re-admission to index hospital. We also compared patient outcomes between patients admitted to index versus non-index hospitals. Results: We identified 27,051 NSTI survivors, of whom 6,954 (25.7%) had an unplanned re-admission within 90 days. A large proportion of re-admission occurred at non-index hospitals (28.3%; n = 1,966). Factors associated with non-index re-admission included prolonged index length of stay, discharge to short-term hospital, and leaving against medical advice. Patients re-admitted to index hospitals had a lower mortality rate (4.7% vs. 6.7%; p = 0.003), lower admission costs (in $1000; 45 [23-88] vs. 50 [24-104]; p = 0.004) and higher discharge rate to home (55.7% vs. 48.6%; p < 0.001). Conclusions: More than one-quarter of re-admissions among NSTI survivors were to non-index hospitals. Continuity of care is important because re-admission to the index hospital was associated with better patient outcomes.

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 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.

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).

Rheology of Polymethylmethacrylate-Collagen Gel Filler: Physiochemical Properties and Clinical Applications.

BACKGROUND: Soft tissue fillers are comprised of a range of materials with differing physiochemical and rheologic (ie, flow) properties. These properties can inform treatment selection for specific anatomic areas, planes of injection, and clinical applications. OBJECTIVES: The aim of this study was to characterize the rheologic properties of polymethylmethacrylate (PMMA)-collagen gel for comparison with other available fillers. METHODS: Commercially available PMMA-collagen gel, hyaluronic acid (HA), and calcium hydroxylapatite (CaHA) fillers were obtained from their respective manufacturers. Measures of complex viscosity (η*) and elastic modulus (G') for each filler were collected at 0.7 Hz in triplicate according to standard procedures on a rotational rheometer fitted with a 40-mm steel plate at 25°C on a Peltier plate (500-µm gap). RESULTS: The measured η* and G' values for HA and CaHA fillers were in agreement with previously published data. The difference in η* between CaHA (mean [standard deviation], 358.9 [21.56] Pa-s) and PMMA-collagen gel (656.41 [68.03] Pa-s) was statistically significant (P < 0.0001), as was the difference between the G' of CaHA (1424.8 [83.3] Pa) and the G' of PMMA-collagen gel (2815.27 [304.07] Pa; P < 0.0001). CONCLUSIONS: PMMA-collagen gel exhibited the highest η* and G' of all tested fillers. These properties likely underpin an increased capacity for lifting and support in areas where long-lasting revolumization is appropriate. In practice, PMMA-collagen gel is well suited for treatment of acne scars, as well as injection into the supraperiosteal plane in the temple, chin, mandible, and piriform by a retrograde linear threading technique. Additional clinical considerations are discussed.

Grade of injury, not initial management, is associated with unplanned interventions in liver injury.

INTRODUCTION: Risk factors for complications after liver injury do not distinguish between patients undergoing selective non-operative management (sNOM) vs operative management (OM) as the initial treatment strategy. Our objective was to identify risk factors for complications requiring an unplanned intervention following sNOM or OM. We hypothesized that patient undergoing sNOM will have fewer unplanned interventions. METHODS: Adults presenting to a level I trauma center with grade III or higher liver injury over a period of 6 years were reviewed. Patient and injury factors, initial management strategy, subsequent complications and interventions were obtained. Bivariate analysis was performed between patients undergoing sNOM vs OM to determine factors associated with unplanned interventions, defined as intervention >48 h after injury. Logistic regression was performed to identify independent risk factors for unplanned interventions. RESULTS: 191 patients were identified: 105 (55%) grade III, 64 (34%) grade IV, and 22 (12%) grade V injury; 136 (71%) underwent sNOM and 55 (29%) underwent OM. 21 (15%) patients required an unplanned intervention: 26 percutaneous drainage, 10 ERCP, and 3 angiography; 12 had multiple procedures. Male gender, younger age, higher ISS, higher grade of injury, firearm mechanism, and initial OM (all p < 0.05) were associated with unplanned interventions. Firearm mechanism and injury grade IV and V, but not initial OM, were independent risk factors for an unplanned intervention. CONCLUSIONS: Grade of liver injury, not the initial mode of treatment, was significantly associated with requiring an unplanned intervention for liver-related complications. Surveillance at 7-10 days, or prior to discharge, in the high-risk group may be able to capture those requiring unplanned intervention and readmission.

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline.

OBJECTIVE: To determine if beta-(ß)-blockers improve outcomes after acute traumatic brain injury (TBI). BACKGROUND: There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with ß-blockers offers a potentially beneficial approach. METHODS: Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was ß-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I). RESULTS: Data were extracted from 9 included studies encompassing 2005 unique TBI patients with ß-blocker treatment and 6240 unique controls. Exposure to ß-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified. CONCLUSIONS: In adults with acute TBI, observational studies reveal a significant mortality advantage with ß-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital ß-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after ß-blocker use for TBI.

Selective nonoperative management of abdominal gunshot wounds with isolated solid organ injury.

OBJECTIVE: To review selective nonoperative management (SNOM) of gunshot wound (GSW) patients with isolated abdominal solid organ injury. METHODS: Patients who sustained isolated solid organ injury secondary to GSW from 2003 to 2014 were studied. The use of SNOM over time was analyzed, and comparisons of initial SNOM and operative management (OM) groups were performed. RESULTS: Of 127 patients, 63 (50%) underwent SNOM. There were no significant differences between the early/late or SNOM/OM groups in demographics, physiologic presentation, or Injury Severity Score. SNOM increased from the early to late cohorts (31%-67%, p < 0.001), without any change in outcomes. SNOM patients had shorter hospital stays (5.8 vs. 10.0 days, p < 0.001), received fewer PRBCs (0.8 vs. 4 units, p < 0.001), and suffered fewer complications (13% vs. 28%, p < 0.05) than the OM group. CONCLUSION: An increase in SNOM vs. OM was associated with equivalent outcomes. Patients undergoing SNOM received fewer PRBCs and had shorter LOS.

Operative fixation of rib fractures after blunt trauma: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Rib fractures are identified in 10% of all injury victims and are associated with significant morbidity (33%) and mortality (12%). Significant progress has been made in the management of rib fractures over the past few decades, including operative reduction and internal fixation (rib ORIF); however, the subset of patients that would benefit most from this procedure remains ill-defined. The aim of this project was to develop evidence-based recommendations. METHODS: Population, intervention, comparison, and outcome (PICO) questions were formulated for patients with and without flail chest. Outcomes of interest included mortality, duration of mechanical ventilation (DMV), hospital and intensive care unit (ICU) length of stay (LOS), incidence of pneumonia, need for tracheostomy, and pain control. A systematic review and meta-analysis of currently available evidence was performed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: Twenty-two studies were identified and analyzed. These included 986 patients with flail chest, of whom 334 underwent rib ORIF. Rib ORIF afforded lower mortality; shorter DMV, hospital LOS, and ICU LOS; and lower incidence of pneumonia and need for tracheostomy. The data quality was deemed very low, with only three prospective randomized trials available. Analyses for pain in patients with flail chest and all outcomes in patients with nonflail chest were not feasible due to inadequate data. CONCLUSION: In adult patients with flail chest, we conditionally recommend rib ORIF to decrease mortality; shorten DMV, hospital LOS, and ICU LOS; and decrease incidence of pneumonia and need for tracheostomy. We cannot offer a recommendation for pain control, or any of the outcomes in patients with nonflail chest with currently available data. LEVEL OF EVIDENCE: Systematic review/meta-analysis, level III.

Management of adult pancreatic injuries: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Traumatic injury to the pancreas is rare but is associated with significant morbidity and mortality, including fistula, sepsis, and death. There are currently no practice management guidelines for the medical and surgical management of traumatic pancreatic injuries. The overall objective of this article is to provide evidence-based recommendations for the physician who is presented with traumatic injury to the pancreas. METHODS: The MEDLINE database using PubMed was searched to identify English language articles published from January 1965 to December 2014 regarding adult patients with pancreatic injuries. A systematic review of the literature was performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to formulate evidence-based recommendations. RESULTS: Three hundred nineteen articles were identified. Of these, 52 articles underwent full text review, and 37 were selected for guideline construction. CONCLUSION: Patients with grade I/II injuries tend to have fewer complications; for these, we conditionally recommend nonoperative or nonresectional management. For grade III/IV injuries identified on computed tomography or at operation, we conditionally recommend pancreatic resection. We conditionally recommend against the routine use of octreotide for postoperative pancreatic fistula prophylaxis. No recommendations could be made regarding the following two topics: optimal surgical management of grade V injuries, and the need for routine splenectomy with distal pancreatectomy. LEVEL OF EVIDENCE: Systematic review, level III.

Management of penetrating extraperitoneal rectal injuries: An Eastern Association for the Surgery of Trauma practice management guideline.

BACKGROUND: The management of penetrating rectal trauma invokes a complex decision tree that advocates the principles of proximal diversion (diversion) of the fecal stream, irrigation of stool from the distal rectum, and presacral drainage based on data from World War II and the Vietnam War. This guideline seeks to define the initial operative management principles for nondestructive extraperitoneal rectal injuries. METHODS: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding penetrating rectal trauma from January 1900 to July 2014. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included the management principles of diversion, irrigation of stool from the distal rectum, and presacral drainage using the GRADE methodology. RESULTS: A total of 306 articles were screened leading to a full-text review of 56 articles. Eighteen articles were used to formulate the recommendations of this guideline. CONCLUSION: This guideline consists of three conditional evidence-based recommendations. First, we conditionally recommend proximal diversion for management of these injuries. Second, we conditionally recommend the avoidance of routine presacral drains and distal rectal washout in the management of these injuries.

Fabrication, nanomechanical characterization, and cytocompatibility of gold-reinforced chitosan bio-nanocomposites.

Chitosan, a naturally derived polymer represents one of the most technologically important classes of active materials with applications in a variety of industrial and biomedical fields. Gold nanoparticles (~32 nm) were synthesized via a citrate reduction method from chloroauric acid and incorporated in Chitosan matrix. Bio-nanocomposite films with varying concentrations of gold nanoparticles were prepared through solution casting process. Uniform distribution of gold nanoparticles was achieved throughout the chitosan matrix and was confirmed with SEM. Synthesis outcomes and prepared nanocomposites were characterized using SEM, TEM, EDX, SAED, UV-vis, XRD, DLS, and Zeta potential for their physical, morphological and structural properties. Nanoscale properties of materials under the influence of temperature were characterized through nanoindentation techniques. From quasi-static nanoindentation, it was observed that hardness and reduced modulus of the nanocomposites were increased significantly in direct proportion to the gold nanoparticle concentration. Gold nanoparticle concentration also showed positive impact on storage modulus and thermal stability of the material. The obtained films were confirmed to be biocompatible by their ability to support growth of human cells in vitro. In summary, the results show enhanced mechanical properties with increasing gold nanoparticle concentration, and provide better understanding of the structure-property relationships of such biocompatible materials for potential biomedical applications.

SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint.

Structural maintenance of chromosomes (SMC) proteins (SMC1, SMC3) are evolutionarily conserved chromosomal proteins that are components of the cohesin complex, necessary for sister chromatid cohesion. These proteins may also function in DNA repair. Here we report that SMC1 is a component of the DNA damage response network that functions as an effector in the ATM/NBS1-dependent S-phase checkpoint pathway. SMC1 associates with BRCA1 and is phosphorylated in response to IR in an ATM- and NBS1-dependent manner. Using mass spectrometry, we established that ATM phosphorylates S957 and S966 of SMC1 in vivo. Phosphorylation of S957 and/or S966 of SMC1 is required for activation of the S-phase checkpoint in response to IR. We also discovered that the phosphorylation of NBS1 by ATM is required for the phosphorylation of SMC1, establishing the role of NBS1 as an adaptor in the ATM/NBS1/SMC1 pathway. The ATM/CHK2/CDC25A pathway is also involved in the S-phase checkpoint activation, but this pathway is intact in NBS cells. Our results indicate that the ATM/NBS1/SMC1 pathway is a separate branch of the S-phase checkpoint pathway, distinct from the ATM/CHK2/CDC25A branch. Therefore, this work establishes the ATM/NBS1/SMC1 branch, and provides a molecular basis for the S-phase checkpoint defect in NBS cells.