The majority of major amputations after resuscitative endovascular balloon occlusion of the aorta are associated with preadmission trauma.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially life-saving intervention. However, recent reports of associations with limb loss and mortality have called its safety into question. We aimed to evaluate patient and hospital characteristics associated with major amputation and in-hospital mortality among patients undergoing REBOA for trauma. METHODS: The National Trauma Data Bank (2015-2017) was queried for patients presenting to trauma centers and treated with REBOA. We included REBOA performed on hospital day 1 in patients who survived 6 or more hours from presentation. Univariable and multivariable analyses evaluated associations with major amputation and in-hospital mortality. RESULTS: A total of 316 patients underwent REBOA and survived in the acute period after presentation. Overall, mean age was 45 ± 20 years and the majority were male (73%) and White (56%). Most patients presented to level I trauma centers (72%) after blunt injuries (79%) with an average Injury Severity Score (ISS) of 31 ± 15, indicating major trauma. In 15 patients (5%), there were 18 major amputations-7 above knee and 11 below knee. A subgroup of 11 amputations were either traumatic amputations (73%) or mangled limbs requiring amputation within 24 hours (27%). Of the remaining amputations, 71% were associated with ipsilateral vascular or orthopedic lower extremity injuries of serious to severe Abbreviated Injury Scale severity. Comparing patients with amputations with those without amputations, there were no significant differences in patient demographics, comorbidities, or hospital characteristics. During hospitalization, patients requiring amputation more frequently received open peripheral vascular interventions (40% vs 10%; P = .002), underwent similar numbers of endovascular interventions (6.7% vs 4.7%; P = .5), and more often developed compartment syndrome (13% vs 2%; P = .04). Overall, there were 110 deaths (35%). The major amputation prevalence was similar between patients who died vs those who survived (3.6% vs 5.3%; P = .5). In multivariable analysis, prehospital cardiac arrest (odds ratio [OR], 8.47; 95% confidence interval [CI], 1.47-48.66; P = .02), penetrating vs blunt trauma (OR, 5.5; 95% CI, 1.05-28.82; P = .04), decreased Glasgow Coma Scale score (OR, 1.18; 95% CI, 1.05-1.32; P = .01), older age (OR, 1.06; 95% CI, 1.03-1.10; P < .001), and increased Injury Severity Score (OR, 1.05; 95% CI, 1.0-1.1; P = .03) were associated with higher mortality. CONCLUSIONS: The majority of major amputations in patients undergoing REBOA were secondary to the initial traumatic mechanism. Injury type and severity, as well as initial hemodynamic derangements, are associated with mortality after REBOA. Despite concerns about prohibitive limb complications of REBOA, baseline injuries seem to be the primary cause of limb loss, but further prospective analysis is needed.

Quality improvement in tracheostomy care: A multidisciplinary approach to standardizing tracheostomy care to reduce complications.

PURPOSE: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications. METHODS: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters. RESULTS: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04). CONCLUSIONS: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points.

Quality Management of massive transfusion protocol incorporating tranexamic acid adherence.

Massive transfusion protocols (MTP) vary at different institutions. We implemented an algorithm in the transfusion service to support our Level I trauma center in 2007 and periodically monitor MTP utilization as part of ongoing quality management. At the last review in 2013, median plasma: RBC ratio was 1:1.8. We undertook a retrospective 3-year review of MTP activations stratifying by trauma versus non-trauma indications, and blood component utilization of the massive transfusion (MT) cases, adding a review of tranexamic acid (TXA) administration to the audit. The median transfused plasma: RBC ratio was 1:1.9 in trauma MT, and 1:1.6 in the non-trauma MT cases. Non-trauma MT patients at our institution were significantly older and more coagulopathic at MTP initiation compared to trauma MT patients, received fewer RBC units (15.5 versus 20.2), and had higher mortality. TXA adherence increased over the 3-year period to 60% of all trauma MTP activations in 2017.

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity.

CT imaging signs of surgically proven bowel trauma.

The objective of this study was to determine the incidence and interobserver agreement of individual CT findings as well as the bowel injury prediction score (BIPS) in surgically proven bowel injury after blunt abdominal trauma. This HIPAA-compliant retrospective study was IRB approved and consent was waived. All patients 14 years or older who sustained surgically proven bowel injury after blunt abdominal trauma between 1/1/2004 and 6/30/2015 were included. Admission trauma MDCT scans were independently interpreted by two abdominal fellowship-trained radiologists who recorded the following CT findings: intraperitoneal fluid, mesenteric hematoma/fat stranding, bowel wall thickening/hematoma, active intravenous contrast extravasation, free intraperitoneal air, bowel wall discontinuity, and focal bowel hypoenhancement. Subsequently, the electronic medical records of the included patients, admission abdominal physical exam results, admission white blood cell count, and findings at exploratory laparotomy of the included patients were recorded. Thirty-three patients met the inclusion criteria. The incidence and interobserver agreement of the CT findings were as follows: intraperitoneal fluid 93.9 %, kappa = 0.784 (good); mesenteric hematoma/fat stranding 84.8 %, kappa = 0.718 (good); bowel wall thickening/hematoma 42.4 %, kappa = 0.491 (moderate); active IV contrast extravasation 36.3 %, kappa = 1.00 (perfect); free intraperitoneal air 21.2 %, kappa = 0.904 (very good), bowel wall discontinuity 6.1 %, kappa = 1.00 (perfect); and focal bowel hypoenhancement 6.1 %, kappa = 0.468 (moderate). An absence of the specified CT findings was encountered in 9.1 % with surgically proven bowel injuries (kappa = 1.00, perfect). In our study, 9/16 patients or 56.3 % had a bowel injury prediction score (BIPS) of 2 or more as defined by McNutt et al. (J Trauma Acute Care Surg 78(1):105-111, 2014). The presence of intraperitoneal fluid and mesenteric hematoma/fat stranding are the most common CT findings in bowel injuries proven at laparotomy. A small percentage of patients have no abnormal CT findings. This grading system did not prove to be useful in our study likely due to our inherently small patient population; however, the use of BIPS deserves further investigation as it may help in identifying blunt bowel and mesenteric injury patients with often subtle or nonspecific CT findings.

Resistance to and killing by the sporicidal microbicide peracetic acid.

OBJECTIVES: To elucidate the mechanisms of spore resistance to and killing by the oxidizing microbicide peracetic acid (PAA). METHODS: Mutants of Bacillus subtilis lacking specific spore structures were used to identify resistance properties in spores and to understand the mechanism of action of PAA. We also assessed the effect of PAA treatment on a number of spore properties including heat tolerance, membrane integrity and germination. RESULTS: The spore coat is essential for spore PAA resistance as spores with defective coats were greatly sensitized to PAA treatment. Small acid-soluble spore proteins apparently provide no protection against PAA. Defects in spore germination, specifically in germination via the GerB and GerK but not the GerA germination receptors, as well as leakage of internal components suggest that PAA is active at the spore inner membrane. It is therefore likely that the inner membrane is the major site of PAA's sporicidal activity. CONCLUSIONS: PAA treatment targets the spore membrane, with some of its activity directed specifically against the GerB and GerK germination receptors.

The role of microRNAs in hepatocyte nuclear factor-4alpha expression and transactivation.

Hepatocyte nuclear factor (HNF)-4α is a key member of the transcription factor network regulating hepatocyte differentiation and function. Genetic and molecular evidence suggests that expression of HNF-4α is mainly regulated at the transcriptional level. Activation of HNF-4A gene involves the interaction of distinct sets of transcription factors and co-transcription factors within enhancer and promoter regions. Here we study the inhibitory effect of microRNAs (miRNAs) on the 3'-untranslated region (3'-UTR) of HNF-4A mRNA. The potential recognition elements of a set of miRNAs were identified utilizing bioinformatics analysis. The family members of miR-34 and miR-449, including miR-34a, miR-34c-5p and miR-449a, share the same target elements located at two distinct locations within the 3'-UTR of HNF-4A. The over-expression of miR-34a, miR-34c-5p or miR-449a in HepG2 cells led to a significant decrease in the activity of luciferase reporter carrying 3'-UTR of HNF-4A. The repressive effect on reporter activity was partially or fully eliminated when one or two of the binding site(s) for miR-34a/miR-34c-5p/miR-449a were deleted within the 3'-UTR. The protein level of HNF-4α was dramatically reduced by over-expression of miR-34a, miR-34c-5p and miR-449a, which correlates with a decrease in the binding activity of HNF-4α and transactivation of HNF-4α target genes. These results suggest that the recognition sites of miR-34a, miR-34c-5p and miR-449a within 3'-UTR of HNF-4A are functional. The mechanism of down-regulation of the binding activity and transactivation of HNF-4α by the miRNAs involves the decrease in HNF-4α protein level via miRNAs selectively targeting HNF-4A 3'-UTR, leading to the translational repression of HNF-4α expression.

Nutritional considerations for head and neck cancer patients: a review of the literature.

PURPOSE: Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer. MATERIALS AND METHODS: A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer. RESULTS: Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented. CONCLUSION: Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect.

Assessment of Risk Factors Correlated with Outcomes of Traumatic Lower Extremity Soft Tissue Reconstruction.

Identifying risk factors for traumatic lower extremity reconstruction outcomes has been limited by sample size. We evaluated patient and procedural characteristics associated with reconstruction outcomes using data from almost four million patients. Methods: The National Trauma Data Bank (2015-2018) was queried for lower extremity reconstructions. Univariable and multivariable analyses determined associations with inpatient outcomes. Results: There were 4675 patients with lower extremity reconstructions: local flaps (77%), free flaps (19.2%), or both (3.8%). Flaps were most commonly local fasciocutaneous (55.1%). Major injuries in reconstructed extremities were fractures (56.2%), vascular injuries (11.8%), and mangled limbs (2.9%). Ipsilateral procedures prereconstruction included vascular interventions (6%), amputations (5.6%), and fasciotomies (4.3%). Postoperative surgical site infection and amputation occurred in 2% and 2.6%, respectively. Among survivors (99%), mean total length of stay (LOS) was 23.2 ± 21.1 days and 46.8% were discharged to rehab. On multivariable analysis, vascular interventions prereconstruction were associated with increased infection [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.05-3.79, P = 0.04], amputation (OR 4.38, 95% CI 2.56-7.47, P < 0.001), prolonged LOS (OR 1.59, 95% CI 1.14-2.22, P = 0.01), and discharge to rehab (OR 1.49, 95% CI 1.07-2.07, P = 0.02). Free flaps were associated with prolonged LOS (OR 2.08, 95% CI 1.74-2.49, P < 0.001). Conclusions: Prereconstruction vascular interventions were associated with higher incidences of adverse outcomes. Free flaps correlated with longer LOS, but otherwise similar outcomes. Investigating reasons for increased complication and healthcare utilization likelihood among these subgroups is warranted.

Application of creatinine height index in patients with trauma for the evaluation of psoas muscle mass: A clinical validation study.

BACKGROUND: The creatinine height index (CHI) is an estimate of lean body mass. We hypothesize that a modified CHI estimate using serum creatinine (sCr) levels in patients with normal renal function when performed soon after injury would reflect preinjury protein nutrition status. METHODS: The urine CHI (uCHI) was calculated using the 24-h urine sample. The serum-derived estimated CHI (sCHI) was calculated using the sCr on admission. Correlation between abdominal computed tomography images at specific lumbar vertebral levels and total body fat and muscle content was used for comparison as an independent measurement of nutrition status unlikely to be substantially altered by trauma. RESULTS: A total of 45 patients were enrolled, all with a significant injury burden (median injury severity score [ISS] = 25; interquartile range, 17-35). The calculated sCHI on admission was 71.0% (SD = 26.9%) and likely underestimates the CHI when compared with uCHI (mean = 112.5%, SD = 32.6%). Stratifying by degree of stress demonstrated that in a group of 23 moderately and severely stressed patients, uCHI (mean = 112.7%, SD = 5.7%) and sCHI (mean = 60.8%, SD = 1.9%) were significantly different and without correlation (r = -0.26, P = 0.91). In patients without stress, there was a significant negative correlation between sCHI and psoas muscle area (r = -0.869, P = 0.03), and in patients with severe stress there was a significant positive correlation between uCHI and psoas muscle area (r = 0.733, P = 0.016). CONCLUSION: The CHI calculated from the initial sCr is not an appropriate estimate of uCHI in critically ill trauma patients and is not a valid measure of psoas muscle mass in this setting.

The Role of the US Trauma Centers in Older Adult Fall Prevention: A National Survey.

INTRODUCTION: Approximately 27.5% of adults 65 and older fall each year, over 3 million are treated in an emergency department, and 32 000 die. The American College of Surgeons and its Committee on Trauma (ACSCOT) have urged trauma centers (TCs) to screen for fall risk, but information on the role of TC in this opportunity for prevention is largely unknown. METHODS: A 29-item survey was developed by an ACSCOT Injury Prevention and Control Committee, Older Adult Falls workgroup, and emailed to 1000 trauma directors of the National Trauma Data Bank using Qualtrics. US TCs were surveyed regarding fall prevention, screening, intervention, and hospital discharge practices. Data collected and analyzed included respondent's role, location, population density, state designation or American College of Surgeons (ACS) level, if teaching facility, and patient population. RESULTS: Of the 266 (27%) respondents, 71% of TCs include fall prevention as part of their mission, but only 16% of TCs use fall risk screening tools. There was no significant difference between geographic location or ACS level. The number of prevention resources (F = 31.58, P < .0001) followed by the presence of a formal screening tool (F = 21.47, P < .0001) best predicted the presence of a fall prevention program. CONCLUSION: Older adult falls remain a major injury risk and injury prevention opportunity. The majority of TCs surveyed include prevention of older adult falls as part of their mission, but few incorporate the components of a fall prevention program. Development of best practices and requiring TCs to screen and offer interventions may prevent falls.

Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α.

BACKGROUND: The hepatic acute phase response(APR) is an organ-specific response to a diverse array of insults and is largely under transcriptional control. Liver-specific transcription factors, hepatic nuclear factors (HNFs)-1α and 4α play important roles in maintenance of liver phenotype and function and their binding activity changes early after injury. However, their roles in modulation of the liver's response over time are not defined. MATERIALS AND METHODS: C57/BL6 mice were anesthetized and exposed to 95°C water for 10 s to create a 15% body surface area full-thickness burn. At specific time points, the mice were sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for fibrinogen-γ and serum amyloid A(SAA)-3 were obtained through polymerase chain reaction (PCR). Transcriptional factor binding activity was assessed with electrophoretic mobility shift assays. RESULTS: Serum IL-6 levels peaked at 3 h and fibrinogen-γ and SAA mRNA levels increased more than 6-fold at 12 h before returning to control levels at 48 h. The binding activity of HNF-4α and HNF-1α rapidly declined after injury (1.5 h) but recovered to near control level at 24 and 6 h, respectively. CONCLUSIONS: Changes in HNF-4α and HNF-1α binding occurred before changes in acute phase protein mRNA levels and were preceded by the peak in IL-6 levels. The rapid suppression and reconstitution of liver-specific transcription factor binding after injury may represent a mechanism that allows the normal liver phenotype to change and an injury-response phenotype to prevail. This mechanism in the liver's adaptive response to injury suggests a central role for both HNF-4α and HNF-1α in transcriptional regulation of the hepatic APR.

Chest X-ray after tracheostomy is not necessary unless clinically indicated.

BACKGROUND: Chest radiography is routinely used post-tracheostomy to evaluate for complications. Often, the chest X-ray findings do not change clinical management. The present study was conducted to evaluate the utility of post-tracheostomy X-rays. METHOD: This retrospective review of 255 patients was performed at a single-center, university, level I trauma center. All patients underwent tracheostomy and were evaluated for postprocedure complications. RESULTS: Of the 255 patients, 95.7% had no change in postprocedure chest X-ray findings. New significant chest X-ray findings were found in 4.3% of patients, including subcutaneous emphysema, pneumothorax, and new significant consolidation. Only three of these patients required change in clinical management, and all changes were based on clinical presentation alone. CONCLUSIONS: Routine chest X-ray following tracheostomy fails to provide additional information beyond clinical examination. Therefore radiographic examination should be performed only after technically difficult procedures or if the patient experiences clinical deterioration. Significant cost savings and minimization of radiation exposure can be achieved when chest radiography after tracheostomy is performed exclusively for clinical indications.

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.

Quantitative analysis of cytokine-induced hepatocyte nuclear factor-4α phosphorylation by mass spectrometry.

Hepatocyte nuclear factor-4α (HNF-4α), a liver-enriched transcription factor, is essential for liver development and function. HNF-4α regulates a large number of liver-specific genes, many of which are modulated by injury. While HNF-4α function is regulated by phosphorylation, only a limited number of phosphorylation sites in HNF-4α have been identified, and the roles of HNF-4α phosphorylation after injury are unexplored. To address these issues, we have carried out an extensive quantitative mass spectrometry (MS)-based analysis of HNF-4α serine and threonine phosphorylation in response to cytokine stimulation. Studies were performed in HNF-4α-enriched HepG2 cells treated with cytokines for 3 h or left untreated, followed by chemical derivatization of the phosphoserine and phosphothreonine residues using stable isotopic variants of dithiothreitol (DTT) and MS analysis. This has allowed the identification and relative quantification of 12 serine/threonine phosphorylation sites in HNF-4α. Eight of these phosphorylation sites and their sensitivity to cytokine stimulation have not been previously reported. We found that cytokine treatment leads to an increase of HNF-4α phosphorylation in several phosphopeptides. The phosphorylation of HNF-4α mediated by protein kinase A (PKA) significantly reduces HNF-4α binding activity, which mimics the repressive effect of cytokines on HNF-4α binding, and the inhibition of PKA activity by PKA inhibitor can partially recover the reduced HNF-4α binding activity induced by cytokines. These results suggest that the mechanism that alters HNF-4α binding after cytokine stimulation involves modulation of specific HNF-4α phosphorylation dependent, in part, on a PKA signaling pathway.

Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α.

BACKGROUND: Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells. RESULTS: The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK). CONCLUSION: The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.

The effects of injury magnitude on the kinetics of the acute phase response.

BACKGROUND: The acute-phase response (APR) is critical to the body's ability to successfully respond to injury. A murine model of closed unilateral femur fractures and bilateral femur fracture were used to study the effect of injury magnitude on this response. METHODS: Standardized unilateral femur fracture and bilateral femur fracture in mice were performed. The femur fracture sites, livers, and serum were harvested over time after injury. Changes in mRNA expression of cytokines, hepatic acute-phase proteins, and serum cytokines overtime were measured. RESULTS: There was a rapid and short-lived hepatic APR to fracture injuries. The overall pattern in both models was similar. Both acute-phase proteins' mRNA (fibrinogen-γ and serum amyloid A-3) showed increased mRNA expression over baseline within the first 48 hours and their levels positively correlated with the extent of injury. However, increased severity of injury resulted in a delayed induction of the APR. A similar effect on the gene expression of cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) at the fracture site was seen. Serum IL-6 levels increased with increased injury and showed no delay between injury models. CONCLUSIONS: Greater severity of injury resulted in a delayed induction of the liver's APR and a diminished expression of cytokines at the fracture site. Serum IL-6 levels were calibrated to the extent of the injury, and changes may represent mechanisms by which the local organ responses to injury are regulated by the injury magnitude.

Amplifying inequity: The compounding impact of COVID-19 and violence.

While "stay-at-home" orders for COVID-19 were in effect, many American cities witnessed a rise in community and interpersonal violence. Our own institution, the largest regional trauma facility and Boston's safety net hospital, saw a paradoxical rise in penetrating violent trauma admissions despite decreases in other hospital admissions, leading to our most violent summer in five years. It has been established that minoritized and marginalized communities have faced the harshest impacts of the pandemic. Our findings suggest that the conditions created by the COVID-19 pandemic have amplified the inequities that exist in communities of color that place them at risk for exposure to violence. The pandemic has served to potentiate the impacts of violence already plaguing the communities and patients we serve.

Clinical diagnostic phenotypes in hospitalizations due to self-inflicted firearm injury.

BACKGROUND: . Hospitalized self-inflicted firearm injuries have not been extensively studied, particularly regarding clinical diagnoses at the index admission. The objective of this study was to discover the diagnostic phenotypes (DPs) or clusters of hospitalized self-inflicted firearm injuries. METHODS: . Using Nationwide Inpatient Sample data in the US from 1993 to 2014, we used International Classification of Diseases, Ninth Revision codes to identify self-inflicted firearm injuries among those ≥18 years of age. The 25 most frequent diagnostic codes were used to compute a dissimilarity matrix and the optimal number of clusters. We used hierarchical clustering to identify the main DPs. RESULTS: . The overall cohort included 14072 hospitalizations, with self-inflicted firearm injuries occurring mainly in those between 16 to 45 years of age, black, with co-occurring tobacco and alcohol use, and mental illness. Out of the three identified DPs, DP1 was the largest (n=10,110), and included most common diagnoses similar to overall cohort, including major depressive disorders (27.7%), hypertension (16.8%), acute post hemorrhagic anemia (16.7%), tobacco (15.7%) and alcohol use (12.6%). DP2 (n=3,725) was not characterized by any of the top 25 ICD-9 diagnoses codes, and included children and peripartum women. DP3, the smallest phenotype (n=237), had high prevalence of depression similar to DP1, and defined by fewer fatal injuries of chest and abdomen. LIMITATIONS: . Claims data. CONCLUSIONS: . There were three distinct diagnostic phenotypes in hospitalizations due to self-inflicted firearm injuries. Further research is needed to determine how DPs can be used to tailor clinical care and prevention efforts.

Diagnosis, management, and pathogenesis of TTP/HUS in an HIV positive patient.

An atypical presentation of HUS/TTP in an HIV positive adult with a prodrome of bloody diarrhea and lack of neurological deficits makes atypical HUS the likely etiology. This case demonstrates the differing treatment modalities for HUS and TTP given the atypical presentation and a discussion of the pathogenesis.