Rectal Injury After Foreign Body Insertion: Secondary Analysis From the AAST Contemporary Management of Rectal Injuries Study Group.

BACKGROUND: Retained rectal foreign bodies are a common but incompletely studied problem. This study defined the epidemiology, injury severity, and outcomes after rectal injuries following foreign body insertion. METHODS: Twenty-two level I trauma centers retrospectively identified all patients sustaining a rectal injury in this AAST multi-institutional trial (2005-2014). Only patients injured by foreign body insertion were included in this secondary analysis. Exclusion criteria were death before rectal injury management or ≤48 h of admission. Demographics, clinical data, and outcomes were collected. Study groups were defined as partial thickness (AAST grade I) versus full thickness (AAST grades II-V) injuries. Subgroup analysis was performed by management strategy (nonoperative versus operative). RESULTS: After exclusions, 33 patients were identified. Mean age was 41 y (range 18-57), and 85% (n = 28) were male. Eleven (33%) had full thickness injuries and 22 (67%) had partial thickness injuries, of which 14 (64%) were managed nonoperatively and 8 (36%) operatively (proximal diversion alone [n = 3, 14%]; direct repair with proximal diversion [n = 2, 9%]; laparotomy without rectal intervention [n = 2, 9%]; and direct repair alone [n = 1, 5%]). Subgroup analysis of outcomes after partial thickness injury demonstrated significantly shorter hospital length of stay (2 ± 1; 2 [1-5] versus 5 ± 2; 4 [2-8] d, P = 0.0001) after nonoperative versus operative management. CONCLUSIONS: Although partial thickness rectal injuries do not require intervention, difficulty excluding full thickness injuries led some surgeons in this series to manage partial thickness injuries operatively. This was associated with significantly longer hospital length of stay. Therefore, we recommend nonoperative management after a retained rectal foreign body unless full thickness injury is conclusively identified.

Impact of the Affordable Care Act on trauma and emergency general surgery: An Eastern Association for the Surgery of Trauma systematic review and meta-analysis.

BACKGROUND: Trauma and emergency general surgery (EGS) patients who are uninsured have worse outcomes as compared with insured patients. Partially modeled after the 2006 Massachusetts Healthcare Reform (MHR), the Patient Protection and Affordable Care Act was passed in 2010 with the goal of expanding health insurance coverage, primarily through state-based Medicaid expansion (ME). We evaluated the impact of ME and MHR on outcomes for trauma patients, EGS patients, and trauma systems. METHODS: This study was approved by the Eastern Association for the Surgery of Trauma Guidelines Committee. Using Grading of Recommendations Assessment, Development and Evaluation methodology, we defined three populations of interest (trauma patients, EGS patients, and trauma systems) and identified the critical outcomes (mortality, access to care, change in insurance status, reimbursement, funding). We performed a systematic review of the literature. Random effect meta-analyses and meta-regression analyses were calculated for outcomes with sufficient data. RESULTS: From 4,593 citations, we found 18 studies addressing all seven predefined outcomes of interest for trauma patients, three studies addressing six of seven outcomes for EGS patients, and three studies addressing three of eight outcomes for trauma systems. On meta-analysis, trauma patients were less likely to be uninsured after ME or MHR (odds ratio, 0.49; 95% confidence interval, 0.37-0.66). These coverage expansion policies were not associated with a change in the odds of inpatient mortality for trauma (odds ratio, 0.96; 95% confidence interval, 0.88-1.05). Emergency general surgery patients also experienced a significant insurance coverage gains and no change in inpatient mortality. Insurance expansion was often associated with increased access to postacute care at discharge. The evidence for trauma systems was heterogeneous. CONCLUSION: Given the evidence quality, we conditionally recommend ME/MHR to improve insurance coverage and access to postacute care for trauma and EGS patients. We have no specific recommendation with respect to the impact of ME/MHR on trauma systems. Additional research into these questions is needed. LEVEL OF EVIDENCE: Review, Economic/Decision, level III.

Traumatic rectal injuries: Is the combination of computed tomography and rigid proctoscopy sufficient?

BACKGROUND: There are no clear guidelines for the best test or combination of tests to identify traumatic rectal injuries. We hypothesize that computed tomography (CT) and rigid proctoscopy (RP) will identify all injuries. METHODS: American Association for the Surgery of Trauma multi-institutional retrospective study (2004-2015) of patients who sustained a traumatic rectal injury. Patients with known rectal injuries who underwent both CT and RP as part of their diagnostic workup were included. Only patients with full thickness injuries (American Association for the Surgery of Trauma grade II-V) were included. Computed tomography findings of rectal injury, perirectal stranding, or rectal wall thickening and RP findings of blood, mucosal abnormalities, or laceration were considered positive. RESULTS: One hundred six patients were identified. Mean age was 32 years, 85(79%) were male, and 67(63%) involved penetrating mechanisms. A total of 36 (34%) and 100 (94%) patients had positive CT and RP findings, respectively. Only 3 (3%) patients had both a negative CT and negative RP. On further review, each of these three patients had intraperitoneal injuries and had indirect evidence of rectal injury on CT scan including pneumoperitoneum or sacral fracture. CONCLUSION: As stand-alone tests, neither CT nor RP can adequately identify traumatic rectal injuries. However, the combination of both test demonstrates a sensitivity of 97%. Intraperitoneal injuries may be missed by both CT and RP, so patients with a high index of suspicion and/or indirect evidence of rectal injury on CT scan may necessitate laparotomy for definitive diagnosis. LEVEL OF EVIDENCE: Diagnostic, level IV.

Civilian Prehospital Tourniquet Use Is Associated with Improved Survival in Patients with Peripheral Vascular Injury.

BACKGROUND: Tourniquet use has been proven to reduce mortality on the battlefield. Although empirically transitioned to the civilian environment, data substantiating survival benefit attributable to civilian tourniquet use is lacking. We hypothesized that civilian prehospital tourniquet use is associated with reduced mortality in patients with peripheral vascular injuries. STUDY DESIGN: We conducted a multicenter retrospective review of all patients sustaining peripheral vascular injuries admitted to 11 Level I trauma centers (January 2011 through December 2016). The study population was divided into 2 groups based on prehospital tourniquet use. Baseline characteristics were compared and factors associated with mortality identified. Logistic regression, adjusting for demographic, physiologic and injury-related parameters, was used to evaluate the association between prehospital tourniquet use and mortality. Delayed amputation was the secondary end point. RESULTS: During 6 years, 1,026 patients with peripheral vascular injuries were admitted. Prehospital tourniquets were used in 181 (17.6%) patients. Tourniquet time averaged 77.3 ± 63.3 minutes (interquartile range 39.0 to 92.3 minutes). Traumatic amputations occurred in 98 patients (35.7% had a tourniquet). Mortality was 5.2% in the non-tourniquet group compared with 3.9% in the tourniquet group (odds ratio 1.36; 95% CI 0.60 to 1.65; p = 0.452). After multivariable analysis, the use of tourniquets was found to be independently associated with survival (adjusted odds ratio 5.86; 95% CI 1.41 to 24.47; adjusted p = 0.015). Delayed amputation rates were not significantly different between the 2 groups (1.1% vs 1.1%; adjusted odds ratio 1.82; 95% CI 0.36 to 9.99; adjusted p = 0.473). CONCLUSIONS: Although still underused, civilian prehospital tourniquet application was independently associated with a 6-fold mortality reduction in patients with peripheral vascular injuries. More aggressive prehospital application of extremity tourniquets in civilian trauma patients with extremity hemorrhage and traumatic amputation is warranted.

Injury patterns and outcomes in late middle age (55-65): The intersecting comorbidity with high-risk activity - A retrospective cohort study.

BACKGROUND: Late middle age (LMA), is a watershed between youth and old age, with unique physical and social changes and declines in vitality, but a desire to remain active despite increasing comorbidity. While post-injury outcomes in the elderly are well studied, little is known regarding LMA patients. We analyzed the injured LMA population admitted to a rural, regional Level 1 Trauma Center relative to outcomes for both younger and older patients. MATERIALS AND METHODS: Our registry was queried retrospectively for patients admitted 7/2008- 12/2015; they were divided into three cohorts: 18-54, 55-65, and >65 years. Demographics, injury details, comorbidities, and outcomes were compiled and compared using ANOVA and Chi-square; p < 0.05 was significant. RESULTS: During the study period, 10,543 were admitted; 1419 (14%) were LMA who experienced overall injury mechanisms, severities and patterns that mirrored the younger cohort. However comorbidity rates were high (56.4%) and comparable to the elderly. LMA patients had the highest rates of alcohol abuse, morbid obesity, and psychiatric illness (p < 0.0001) and suffered the poorest outcomes: highest complications and hospital charges, and longest ICU and hospital LOS. LMA mortality (4.1%) was 41% higher than younger patients (2.9%; p < 0.02) and similar to the older cohort (4.7%; p = 0.32). CONCLUSIONS: The LMA population has similar mechanisms and injury patterns to younger patients, while exhibiting comorbidity rates similar to the elderly. High-energy injuries exact a greater toll in LMA with poorer outcomes and greater resource utilization. Targeted outreach for injury prevention, and future studies, are needed to address high-risk behavior, substance abuse, and societal contributors.

Contemporary management of rectal injuries at Level I trauma centers: The results of an American Association for the Surgery of Trauma multi-institutional study.

INTRODUCTION: Rectal injuries have been historically treated with a combination of modalities including direct repair, resection, proximal diversion, presacral drainage, and distal rectal washout. We hypothesized that intraperitoneal rectal injuries may be selectively managed without diversion and the addition of distal rectal washout and presacral drainage in the management of extraperitoneal injuries are not beneficial. METHODS: This is an American Association for the Surgery of Trauma multi-institutional retrospective study from 2004 to 2015 of all patients who sustained a traumatic rectal injury and were admitted to one of the 22 participating centers. Demographics, mechanism, location and grade of injury, and management of rectal injury were collected. The primary outcome was abdominal complications (abdominal abscess, pelvic abscess, and fascial dehiscence). RESULTS: After exclusions, there were 785 patients in the cohort. Rectal injuries were intraperitoneal in 32%, extraperitoneal in 58%, both in 9%, and not documented in 1%. Rectal injury severity included the following grades I, 28%; II, 41%; III, 13%; IV, 12%; and V, 5%. Patients with intraperitoneal injury managed with a proximal diversion developed more abdominal complications (22% vs 10%, p = 0.003). Among patients with extraperitoneal injuries, there were more abdominal complications in patients who received proximal diversion (p = 0.0002), presacral drain (p = 0.004), or distal rectal washout (p = 0.002). After multivariate analysis, distal rectal washout [3.4 (1.4-8.5), p = 0.008] and presacral drain [2.6 (1.1-6.1), p = 0.02] were independent risk factors to develop abdominal complications. CONCLUSION: Most patients with intraperitoneal injuries undergo direct repair or resection as well as diversion, although diversion is not associated with improved outcomes. While 20% of patients with extraperitoneal injuries still receive a presacral drain and/or distal rectal washout, these additional maneuvers are independently associated with a three-fold increase in abdominal complications and should not be included in the treatment of extraperitoneal rectal injuries. LEVEL OF EVIDENCE: Therapeutic study, level III.

A comparison of initial lactate and initial base deficit as predictors of mortality after severe blunt trauma.

BACKGROUND: After injury, base deficit (BD) and lactate are common measures of shock. Lactate directly measures anaerobic byproducts, whereas BD is calculated and multifactorial. Although recent studies suggest superiority for lactate in predicting mortality, most were small or analyzed populations with heterogeneous injury severity. Our objective was to compare initial BD with lactate as predictors of inhospital mortality in a large cohort of blunt trauma patients all presenting with hemorrhagic shock. MATERIALS AND METHODS: The Glue Grant multicenter prospective cohort database was queried; demographic, injury, and physiologic parameters were compiled. Survivors, early deaths (≤24 h), and late deaths were compared. Profound shock (lactate ≥ 4 mmol/L) and severe traumatic brain injury subgroups were identified a priori. Chi-square, t-test, and analysis of variance were used as appropriate for analysis. Multivariable logistic regression and area under the receiver operating characteristic curve analysis assessed survival predictors. P < 0.05 was significant. RESULTS: A total of 1829 patients met inclusion; 289 (15.8%) died. Both BD and lactate were higher for nonsurvivors (P < 0.00001). After multivariable regression, both lactate (odds ratio [OR] 1.17; 95% confidence interval [CI]: 1.12-1.23; P < 0.00001) and BD (OR 1.04; 95% CI: 1.01-1.07; P < 0.005) predicted overall mortality. However, when excluding early deaths (n = 77), only lactate (OR 1.12 95% CI: 1.06-1.19; P < 0.0001) remained predictive but not BD (OR 1.00 95% CI: 0.97-1.04; P = 0.89). For the shock subgroup, (n = 915), results were similar with lactate, but not BD, predicting both early and late deaths. Findings also appear independent of traumatic brain injury severity. CONCLUSIONS: After severe blunt trauma, initial lactate better predicts inhospital mortality than initial BD. Initial BD does not predict mortality for patients who survive >24 h.

Impact of transfer distance and time on rural brain injury outcomes.

OBJECTIVES: After rural injury, evaluation at local hospitals with transfer to regional trauma centres may delay definitive care. This study sought to determine the impact of such delays on outcomes in patients with TBI within a mature regional trauma system. METHODS: The ETMC Level 1 Trauma registry was queried from 2008-2013 for patients with blunt TBI, aged ≥ 18 and admitted ≤ 24 hours from injury and stratified them as 'transfer' vs 'direct' admission. Demographics, transfer distance, transfer times and outcomes were compared using Chi-square, t-test and multivariable logistic regression; p < 0.05 was significant. RESULTS: During the study period, 1845 patients met inclusion criteria: 947 'direct' and 898 'transfers'. For transfers, median distance was 60.1 miles; mean time to initial care was 1.2 ± 2.7 hours and time to Level 1 care was 5.0 ± 2.4 hours. Transfer patients were older (56 vs 49 years; p < 0.01) and had more comorbidities, but had lower mean ISS (15.9 vs 18.8; p < 0.01) and lower mortality (7.0 vs 10.3%; p < 0.03), complications and LOS. Neurosurgical intervention was comparable (p = 0.88), as was mortality for patients with ISS ≥ 15 (12.4% vs 14.8%; p = 0.28). After regression analysis, advanced age and increasing ISS, not distance or time, predicted mortality. CONCLUSION: Neither transfer distance nor time independently contributed to mortality for TBI after rural injury. An established regional trauma system, with initial local stabilization using ATLS principles, may help reduce negative outcomes for injured patients in rural settings.

FabAV antivenin use after copperhead snakebite: clinically indicated or knee-jerk reaction?

BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) antivenin is commonly recommended after pit viper snakebites. Because copperhead envenomations are usually self-limited, some physicians are reluctant to use this costly treatment routinely, while others follow a more liberal approach. We hypothesized that, in practice, only patients with evidence of significant (moderate or severe) copperhead envenomation [those with snakebite severity score (SSS) > 3] receive FabAV and examined a large cohort to determine the relationship between clinical findings and FabAV administration. METHODS: All data from patients evaluated for copperhead snakebite at a rural tertiary referral center from 5/2002 to 10/2013 were compiled. Demographics, transfer status, antivenin use, and clinical findings were collected; SSS was calculated. The relationships among FabAV use, clinical findings, and SSS were analyzed using t-test, chi-square, and Pearson's coefficient (p < 0.05 was significant). RESULTS: During the study period, 318 patients were treated for copperhead snakebite; 44 (13.8 %) received antivenin. Median dose was four vials (range: 1-10; IQR: 4,6). There were no deaths. Most patients receiving FabAV (63.6 %) were admitted. With regard to demographics and symptoms, only the degree of swelling (moderate vs. none/mild; p < 0.01) and bite location (hand/arm vs. leg: p < 0.0001) were associated with FabAV use. A SSS > 3, indicating moderate or severe envenomation, was only very weakly correlated with antivenin use (r = 0.217; p < 0.0001). The majority of patients with SSS > 3 (65.8 %) did not receive antivenin while most patients who did receive antivenin (70.5 %) had SSS ≤ 3 (indicating mild envenomation). CONCLUSIONS: Considerable variation occurs in antivenin administration after copperhead snakebite. Use of FabAV appears poorly correlated with patients' symptoms. This practice may expose patients to the risks of antivenin and increasing costs of medical care without improving outcomes. Guidelines used for treating other pit viper strikes, such as rattlesnake or cottonmouth snakebite may be too liberal for copperhead envenomations. Our data suggests that most patients with mild or moderate envenomation appear to do well independent of FabAV use. We suggest, for patients with copperhead snakebite, that consideration be given to withholding FabAV for those without clinical evidence of severe envenomation until prospective randomized data are available.

FabAV antivenin use after copperhead snakebite: clinically indicated or knee-jerk reaction?

Abstract Background Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) antivenin is commonly recommended after pit viper snakebites. Because copperhead envenomations are usually self-limited, some physicians are reluctant to use this costly treatment routinely, while others follow a more liberal approach. We hypothesized that, in practice, only patients with evidence of significant (moderate or severe) copperhead envenomation [those with snakebite severity score (SSS) > 3] receive FabAV and examined a large cohort to determine the relationship between clinical findings and FabAV administration. Methods All data from patients evaluated for copperhead snakebite at a rural tertiary referral center from 5/2002 to 10/2013 were compiled. Demographics, transfer status, antivenin use, and clinical findings were collected; SSS was calculated. The relationships among FabAV use, clinical findings, and SSS were analyzed using t-test, chi-square, and Pearson’s coefficient (p < 0.05 was significant). Results During the study period, 318 patients were treated for copperhead snakebite; 44 (13.8 %) received antivenin. Median dose was four vials (range: 1–10; IQR: 4,6). There were no deaths. Most patients receiving FabAV (63.6 %) were admitted. With regard to demographics and symptoms, only the degree of swelling (moderate vs. none/mild; p < 0.01) and bite location (hand/arm vs. leg: p < 0.0001) were associated with FabAV use. A SSS > 3, indicating moderate or severe envenomation, was only very weakly correlated with antivenin use (r = 0.217;p < 0.0001). The majority of patients with SSS > 3 (65.8 %) did not receive antivenin while most patients who did receive antivenin (70.5 %) had SSS ≤ 3 (indicating mild envenomation). Conclusions Considerable variation occurs in antivenin administration after copperhead snakebite. Use of FabAV appears poorly correlated with patients’ symptoms. This practice may expose patients to the risks of antivenin and increasing costs of medical care without improving outcomes. Guidelines used for treating other pit viper strikes, such as rattlesnake or cottonmouth snakebite may be too liberal for copperhead envenomations. Our data suggests that most patients with mild or moderate envenomation appear to do well independent of FabAV use. We suggest, for patients with copperhead snakebite, that consideration be given to withholding FabAV for those without clinical evidence of severe envenomation until prospective randomized data are available.

FabAV antivenin use after copperhead snakebite: clinically indicated or knee-jerk reaction?

Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) antivenin is commonly recommended after pit viper snakebites. Because copperhead envenomations are usually self-limited, some physicians are reluctant to use this costly treatment routinely, while others follow a more liberal approach. We hypothesized that, in practice, only patients with evidence of significant (moderate or severe) copperhead envenomation [those with snakebite severity score (SSS) > 3] receive FabAV and examined a large cohort to determine the relationship between clinical findings and FabAV administration. Methods All data from patients evaluated for copperhead snakebite at a rural tertiary referral center from 5/2002 to 10/2013 were compiled. Demographics, transfer status, antivenin use, and clinical findings were collected; SSS was calculated. The relationships among FabAV use, clinical findings, and SSS were analyzed using t-test, chi-square, and Pearsons coefficient (p 0.05 was significant). Results During the study period, 318 patients were treated for copperhead snakebite; 44 (13.8 %) received antivenin. Median dose was four vials (range: 110; IQR: 4,6). There were no deaths. Most patients receiving FabAV (63.6 %) were admitted. With regard to demographics and symptoms, only the degree of swelling (moderate vs. none/mild; p 0.01) and bite location (hand/arm vs. leg: p 0.0001) were associated with FabAV use. A SSS > 3, indicating moderate or severe envenomation, was only very weakly correlated with antivenin use (r = 0.217;p 0.0001). The majority of patients with SSS > 3 (65.8 %) did not receive antivenin while most patients who did receive antivenin (70.5 %) had SSS 3 (indicating mild envenomation). Conclusions Considerable variation occurs in antivenin administration after copperhead snakebite. Use of FabAV appears poorly correlated with patients symptoms. This practice may expose patients to the risks of antivenin and increasing costs of medical care without improving outcomes. Guidelines used for treating other pit viper strikes, such as rattlesnake or cottonmouth snakebite may be too liberal for copperhead envenomations. Our data suggests that most patients with mild or moderate envenomation appear to do well independent of FabAV use. We suggest, for patients with copperhead snakebite, that consideration be given to withholding FabAV for those without clinical evidence of severe envenomation until prospective randomized data are available.

The financial burden of emergency general surgery: National estimates 2010 to 2060.

BACKGROUND: Adoption of the acute care surgery model has led to increasing volumes of emergency general surgery (EGS) patients at trauma centers. However, the financial burden of EGS services on trauma centers is unknown. This study estimates the current and future costs associated with EGS hospitalization nationwide. METHODS: We applied the American Association for the Surgery of Trauma's DRG International Classification of Diseases-9th Rev. criteria for defining EGS to the 2010 National Inpatient Sample (NIS) data and identified adult EGS patients. Cost of hospitalization was obtained by converting reported charges to cost using the 2010 all-payer inpatient cost-to-charge ratio for all hospitals in the NIS database. Cost was modeled via a log-gamma model in a generalized linear mixed model to account for potential correlation in cost within states and hospitals in the NIS database. Patients' characteristics and hospital factors were included in the model as fixed effects, while state and hospital were included as random effects. The national incidence of EGS was calculated from NIS data, and the US Census Bureau population projections were used to estimate incidence for 2010 to 2060. Nationwide costs were obtained by multiplying projected incidences by estimated costs and reported in year 2010 US dollar value. RESULTS: Nationwide, there were 2,640,725 adult EGS hospitalizations in 2010. The national average adjusted cost per EGS hospitalization was $10,744 (95% confidence interval [CI], $10,615-$10,874); applying these cost data to the national EGS hospitalizations gave a total estimated cost of $28.37 billion (95% CI, $28.03-$28.72 billion). Older age groups accounted for greater proportions of the cost ($8.03 billion for age ≥ 75 years, compared with $1.08 billion for age 18-24 years). As the US population continues to both grow and age, EGS costs are projected to increase by 45% to $41.20 billion (95% CI, $40.70-$41.7 billion) by 2060. CONCLUSION: EGS constitutes a significant portion of US health care costs and is expected to rise with the demographic changes in the population. Trauma centers should conduct careful financial analyses of their EGS services, based on their unique case mix and payer mix. LEVEL OF EVIDENCE: Economic analysis, level III.

Diverticulitis Outcomes are Equivalent Between Level 1 Trauma Centers and Community Hospitals in New Jersey.

Traditionally, general surgeons provide emergency general surgery (EGS) coverage by assigned call. The acute care surgery (ACS) model is new and remains confined mostly to academic centers. Some argue that in busy trauma centers, on-call trauma surgeons may be unable to also care for EGS patients. In New Jersey, all three Level 1 Trauma Centers (L1TC) have provided ACS services for many years. Analyzing NJ state inpatient data, we sought to determine whether outcomes in one common surgical illness, diverticulitis, have been different between L1TC and nontrauma centers (NTC) over a 10-year period. The NJ Medical Database was queried for patients aged 18 to 90 hospitalized from 2001 to 2010 for acute diverticulitis. Demographics, comorbidities, operative rates, and mortality were compiled and analyzed comparing L1TC to NTC. For additional comparison between L1TC and NTC, 1:1 propensity score matching with replacement was accomplished. χ(2), t test, and Cochran-Armitage trend test were used. From 2001 to 2010, 88794 patients were treated in NJ for diverticulitis. 2621 patients (2.95%) were treated at L1TCs. Operative rates were similar between hospital types. Patients treated at L1TCs were more often younger (63.1 ± 0.3 vs 64.7 ± 0.1; P < 0.001), nonwhite (43.1% vs 23.1%; P < 0.0001), and uninsured (11.0% vs 5.5%; P < 0.0001). After propensity matching, neither operative mortality (9.7% vs 7.9% P = 0.45), nor nonoperative mortality (1.2% vs 1.3% P = 0.60) were different between groups. Mortality and operative rates for patients with acute diverticulitis are equivalent between LT1C and NTC in NJ. Trauma centers in NJ more commonly provide care to minority and uninsured patients.

Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.

INTRODUCTION: Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV. METHODS: Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40. RESULTS: The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor α and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. CONCLUSIONS: By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

The public health burden of emergency general surgery in the United States: A 10-year analysis of the Nationwide Inpatient Sample--2001 to 2010.

BACKGROUND: Emergency general surgery (EGS) represents illnesses of very diverse pathology related only by their urgent nature. The growth of acute care surgery has emphasized this public health problem, yet the true "burden of disease" remains unknown. Building on efforts by the American Association for the Surgery of Trauma to standardize an EGS definition, we sought to describe the burden of disease for EGS in the United States. We hypothesize that EGS patients represent a large, diverse, and challenging cohort and that the burden is increasing. METHODS: The study population was selected from the Nationwide Inpatient Sample, 2001 to 2010, using the AAST EGS DRG International Classification of Diseases-9th Rev. codes, selecting all EGS patients 18 years or older with urgent/emergent admission status. Rates for operations, mortality, and sepsis were compiled along with hospital type, length of stay, insurance, and demographic data. The χ test, the t test, and the Cochran-Armitage trend test were used; p < 0.05 was significant. RESULTS: From 2001 to 2010, there were 27,668,807 EGS admissions, 7.1% of all hospitalizations. The population-adjusted case rate for 2010 was 1,290 admissions per 100,000 people (95% confidence interval, 1,288.9-1,291.8). The mean age was 58.7 years; most had comorbidities. A total of 7,979,578 patients (28.8%) required surgery. During 10 years, admissions increased by 27.5%; operations, by 32.3%; and sepsis cases, by 15% (p < 0.0001). Mortality and length of stay both decreased (p < 0.0001). Medicaid and uninsured rates increased by a combined 38.1% (p < 0.0001). Nearly 85% were treated in urban hospitals, and nearly 40% were treated in teaching hospitals; both increased over time (p < 0.0001). CONCLUSION: The EGS burden of disease is substantial and is increasing. The annual case rate (1,290 of 100,000) is higher than the sum of all new cancer diagnoses (all ages/types): 650 per 100,000 (95% confidence interval, 370.1-371.7), yet the public health implications remain largely unstudied. These data can be used to guide future research into improved access to care, resource allocation, and quality improvement efforts. LEVEL OF EVIDENCE: Epidemiologic study, level III.

APOε4 is associated with enhanced in vivo innate immune responses in human subjects.

BACKGROUND: The genetic determinants of the human innate immune response are poorly understood. Apolipoprotein (Apo) E, a lipid-trafficking protein that affects inflammation, has well-described wild-type (ε3) and disease-associated (ε2 and ε4) alleles, but its connection to human innate immunity is undefined. OBJECTIVE: We sought to define the relationship of APOε4 to the human innate immune response. METHODS: We evaluated APOε4 in several functional models of the human innate immune response, including intravenous LPS challenge in human subjects, and assessed APOε4 association to organ injury in patients with severe sepsis, a disease driven by dysregulated innate immunity. RESULTS: Whole blood from healthy APOε3/APOε4 volunteers induced higher cytokine levels on ex vivo stimulation with Toll-like receptor (TLR) 2, TLR4, or TLR5 ligands than blood from APOε3/APOε3 patients, whereas TLR7/8 responses were similar. This was associated with increased lipid rafts in APOε3/APOε4 monocytes. By contrast, APOε3/APOε3 and APOε3/APOε4 serum neutralized LPS equivalently and supported similar LPS responses in Apoe-deficient macrophages, arguing against a differential role for secretory APOE4 protein. After intravenous LPS, APOε3/APOε4 patients had higher hyperthermia and plasma TNF-α levels and earlier plasma IL-6 than APOε3/APOε3 patients. APOE4-targeted replacement mice displayed enhanced hypothermia, plasma cytokines, and hepatic injury and altered splenic lymphocyte apoptosis after systemic LPS compared with APOE3 counterparts. In a cohort of 828 patients with severe sepsis, APOε4 was associated with increased coagulation system failure among European American patients. CONCLUSIONS: APOε4 is a determinant of the human innate immune response to multiple TLR ligands and associates with altered patterns of organ injury in human sepsis.

Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.

Previously, we have shown that systemic insults in single injury models produced immunosuppressive effects in burn, and a strong acute phase response in sepsis through hepatic gene expression. In order to investigate the implications of these effects on a combined injury, a double hit model was explored to mimic the progression of clinical burn-sepsis. Rodents were subjected to a 20% total body surface area (TSA) full-thickness burn injury, and 48 hours later underwent cecal ligation and puncture (CLP) to induce sepsis. Pathways related to innate immune signaling through cytokines and NF-KB were co regulated with xenobiotic metabolism genes and acute phase protein genes, and that these genes were suppressed early, and then activated. Furthermore, we were able to identify that, in addition to amino acid metabolism, pyruvate metabolism, fatty acid metabolism and NRF-2 mediated oxidative stress genes were down regulated over the time course. Overall, these observed trends within the double hit burn-sepsis model represent unique immune and metabolic pathways and dynamics not found in either injury, including an early suppression followed by overreaction of pro inflammatory mediators, and an increase in amino acid metabolism at the expense of central carbon pathways.