Glucose-fed microbiota alters C. elegans intestinal epithelium and increases susceptibility to multiple bacterial pathogens.

Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.

Trauma Surgeons Experience Compassion Fatigue - A Major Metropolitan Area Survey.

INTRODUCTION: Compassion Fatigue (CF), the physical, emotional, and psychological impact of helping others, is composed of three domains: Compassion Satisfaction (CS), Secondary Traumatic Stress (STS), and Burnout (BO). Trauma surgeons (TS) experience work-related stress resulting in high rates of CF which can manifest as physical and psychological disorders. We hypothesized that TS experience CF and there are potentially modifiable systemic factors to mitigate its symptoms. METHODS: All TS in a major metropolitan area were eligible. Personal and professional demographic information was obtained. Each participant completed six validated surveys: 1) Professional Quality of Life Scale (Pro-QOL), 2) Perceived Stress Scale (PSS), 3) Multidimensional Scale of Perceived Social Support (MSPSS), 4) Adverse Childhood Events (ACE) Questionnaire, 5) Brief Coping Inventory (BCI), and 6) Toronto Empathy Questionnaire (TEQ). CF subscale risk scores (low:<23, moderate:23-41, high:>41) were recorded. Linear regression analysis assessed the demographic and environmental factors association with BO, STS, and CS. Variables significant on univariate analysis were included in multivariate models to determine the independent influence on BO, STS, and CS. Significance was p ≤ 0.05. RESULTS: There were 57 TS (response rate:75.4% (n = 43); Caucasian: 65% (n = 28), male:67% (n = 29)). TS experienced CF (BO:26 (IQR: 21-32), STS:23 (IQR: 19-32), CS:39 (IQR: 34-45)). The PSS score was significantly associated with increased BO (Coef: 0.52, 95% CI: 0.28-0.77) and STS (Coef: 0.44. 95% CI: 0.15-0.73), and decreased CS (Coef: -0.51, 95% CI: -0.80- -0.23) (p < 0.01). Night shifts were associated with higher BO (Coef: 1.55, 95% CI: 0.07-3.03, p = 0.05), conversely day shifts were associated with higher STS (Coef: 1.94, 95% CI: 0.32-3.56, p = 0.03). Higher TEQ scores were associated with greater CS (Coef: 0.33, 95% CI: 0.12-0.55, p < 0.01). CONCLUSION: TS experience moderate BO and STS associated with modifiable system- and work-related stressors. Efforts to reduce CF should focus on addressing sources of workplace stress and promoting empathic care. LEVEL OF EVIDENCE: III, Prognostic and Epidemiological.

The tight rope act: A multicenter regional experience of tourniquets in acute trauma resuscitation.

BACKGROUND: As tourniquets have become more prevalent, device use has been questioned. This study sought to characterize the incidence, indication, and efficacy of tourniquet placement in acute trauma resuscitation. METHODS: Nine regional level 1 trauma centers prospectively enrolled for 12 months adult patients (18 years or older) who had a tourniquet placed. Age, sex, mechanism, tourniquet type, indication, applying personnel, location placed, level of occlusion, and degree of hemostasis were collected. Major vascular injury, imaging and operations performed, and outcomes were assessed. Analyses were performed with significance at p < 0.05. RESULTS: A total of 216 tourniquet applications were reported on 209 patients. There were significantly more male patients (183 [88%]) and penetrating injuries (186 [89%]) with gunshots being most common (127 [61%]). Commercial tourniquets were most often used (205 [95%]). Ninety-two percent were placed in the prehospital setting (by fire/paramedics, 56%; police, 33%; bystanders, 2%). The most common indications were pooling (47%) and pulsatile (32%) hemorrhage. Only 2% were for amputation. The most frequent location was high proximal extremity (70%). Four percent were placed over the wound, and 0.5% were distal to the wound. Only 61% of applications were arterial occlusive. Median application time was 30 minutes (interquartile range, 20-40 minutes). Imaging was performed in 54% of patients. Overall, 36% had a named arterial injury. Tourniquet application failed to achieve hemostasis in 22% of patients with a named vascular injury. There was no difference in hemostasis between those with and without vascular injury (p = 0.12) or between who placed the tourniquet (p = 0.07). Seventy patients (34%) required vascular operations. Thirty-four percent of patients were discharged home without admission. CONCLUSION: Discerning which injuries require tourniquets over pressure dressings remains elusive. Trained responders had high rates of superfluous and inadequate deployments. As tourniquets continue to be disseminated, emphasis should be placed on improving education, device development, and quality control. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level III.

Bacterial processing of glucose modulates C. elegans lifespan and healthspan.

Intestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. Our data reveal that bacterial processing of glucose results in reduced lifespan and healthspan including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. With chronic exposure to glucose, E. coli exhibits growth defects and increased advanced glycation end products. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of the glutathione-S-transferase, gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose fed bacterial diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

Obesity is Not Associated With Need for Skin Grafting After Hidradenitis Excision.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating disease associated with inflammation, recurrent abscesses, and fistulae of skin containing apocrine sweat glands. We hypothesize that the need for skin grafting after vacuum-assisted closure was decreased with increasing body mass index (BMI). METHODS: Seventy-one consecutive patients with excisions for HS were retrospectively evaluated for demographic data, number of excisions, the total area of excised skin, need for skin grafting, and BMI. Patients were stratified for BMI and underwent logistic regression to compare all other variables. RESULTS: Average for BMI was 30.8 ± 7.72, age was 36.89 ±13.52, area excised was 743 cm2 ± 774 cm2, mean operating room trips were 2.62 ± 1.59, and skin grafting was 0.52 ± 0.55. Patients were 60% male. Forty out of 71 patients were obese. There was no correlation between age, BMI, sex, thenumber of excisions, amount of skin excised, or need for a skin graft. There was a statistically significant relationship between the amount of skin excised and the need for skin grafting (P = .006). CONCLUSIONS: The amount of skin affected by HS appears to be independent of patient BMI. The need for skin grafting is solely dependent upon the amount of tissue excised. APPLICABILITY OF RESEARCH TO PRACTICE: This knowledge will help preoperative planning for all patients with HS, regardless of BMI.

Blunt trauma pelvic fracture-associated genitourinary and concomitant lower gastrointestinal injury: incidence, morbidity, and mortality.

PURPOSE: Limited data exist on the characteristics, risk factors, and management of blunt trauma pelvic fractures causing genitourinary (GU) and lower gastrointestinal (GI) injury. We sought to determine these parameters and elucidate independent risk factors. METHODS: The National Trauma Data Bank for years 2010-2014 was queried for pelvic fractures by ICD-9-CM codes. Exclusion criteria included age ≤ 17 years, penetrating injury, or incomplete records. Patients were divided into three cohorts: pelvic fracture, pelvic fracture with GU injury, and pelvic fracture with GU and GI injury. Between-group comparisons were made using stratified analysis. Multivariable logistic regression was used to determine independent risk factors for concomitant GI injury. RESULTS: In total, 180,931 pelvic fractures were found, 3.3% had GU, and 0.15% had GU and GI injury. Most common mechanism was vehicular collision. Injury severity score, pelvic AIS, and mortality were higher with combined injury (p < 0.001), leading to longer hospital and ICU stays and ventilator days (p < 0.001) with more frequent discharges to acute rehabilitation (p < 0.01). Surgical management of concomitant injuries involved both urinary (62%) and rectal repairs (81%) or diversions (29% and 46%, respectively). Male gender (OR = 2.42), disruption of the pelvic circle (OR = 6.04), pubis fracture (OR = 2.07), innominate fracture (OR = 1.84), and SBP < 90 mmgh (OR = 1.59) were the strongest independent predictors of combined injury (p < 0.01). CONCLUSION: Pelvic fractures with lower GU and GI injury represent < 1% of pelvic fractures. They are associated with more severe injuries and increased hospital resource utilization. Strongest independent predictors are disruption of the pelvic circle, male gender, innominate fracture, and SBP < 90mm Hg.

Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans.

As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans, excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C. elegans glycogen synthase, gsy-1, a key enzyme in glycogen synthesis, can extend lifespan, prolong healthspan, and limit the detrimental effects of a high-sugar diet. Importantly, limiting glycogen storage leads to a metabolic shift whereby glucose is now stored as trehalose. Two additional means to increase trehalose show similar longevity extension. Increased trehalose is entirely dependent on a functional FOXO transcription factor DAF-16 and autophagy to promote lifespan and healthspan extension. Our results reveal that when glucose is stored as glycogen, it is detrimental, whereas, when stored as trehalose, animals live a longer, healthier life if DAF-16 is functional. Taken together, these results demonstrate that trehalose modulation may be an avenue for combatting high-sugar-diet pathology.

Marjolin's Ulcer in Chronic Hidradenitis Suppurativa: A Rare Complication of an Often Neglected Disease.

Hidradenitis suppurativa (HS) is a chronic, debilitating disease with definitive treatment consisting of wide surgical excision of all affected tissue. Originally described in burns, Marjolin's ulcer (MU) has been described in a variety of wound types, including hidradenitis. HS patients often have long delays to diagnosis and management of their chronic wounds, leading to increased risk of MU. A retrospective review of our burn database was performed from 2008 to 2014. Seventy-two consecutive patients taken to the operating room for HS were retrospectively evaluated for demographic data, number of excisions, total area of excised skin, need for skin grafting, pathology results, and outcome. Fifty-eight percent of patients were male. Mean age was 36.88 ± 13.52 years. Mean size of excision was 743.71 ± 774.75 cm. Total number of operative procedures was 187, averaging 2.612 per patient, with 52% of patients undergoing skin grafting. Two patients had confirmed pathology of squamous cell carcinoma. Both were women with perineal HS and had metastatic disease on further workup. Both patients underwent chemotherapy and radiation with progression of their disease. The incidence of MU of 2.78% in this study is similar to the 2% incidence described historically in the burn population. All practitioners who treat HS patients should be aware of the devastating complication of MU arising in the chronic wound bed. We recommend that all excised tissue be sent to pathology for evaluation, and to consider early wide local excision of any chronically inflamed tissues to alleviate the risk of MU for this patient population.

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.

Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity.

In the nematode Caenorhabditis elegans, inactivating mutations in the insulin/IGF-1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a FOXO-family transcription factor. Downstream protein activities that directly regulate longevity during impaired insulin/IGF-1 signaling (IIS) are poorly characterized. Here, we use global cysteine-reactivity profiling to identify protein activity changes during impaired IIS. Upon confirming that cysteine reactivity is a good predictor of functionality in C. elegans, we profiled cysteine-reactivity changes between daf-2 and daf-16;daf-2 mutants, and identified 40 proteins that display a >2-fold change. Subsequent RNAi-mediated knockdown studies revealed that lbp-3 and K02D7.1 knockdown caused significant increases in lifespan and dauer formation. The proteins encoded by these two genes, LBP-3 and K02D7.1, are implicated in intracellular fatty acid transport and purine metabolism, respectively. These studies demonstrate that cysteine-reactivity profiling can be complementary to abundance-based transcriptomic and proteomic studies, serving to identify uncharacterized mediators of C. elegans longevity.

Trans-abdominal wall traction as a universal solution to the management of giant ventral hernias.

BACKGROUND: Domain loss following damage-control laparotomy is a challenging problem many surgeons face. The authors recently developed trans-abdominal wall traction, which closed 100 percent of domain loss abdomens in the acute setting. They hypothesized that it can be used successfully in patients with chronic giant ventral defects. METHODS: From 2008 to 2013, 44 patients with acute loss of domain and 10 with chronically giant ventral defects were enrolled in the open abdomen protocol with subsequent placement of the trans-abdominal wall traction device. RESULTS: Patients' average age in the acute and chronic groups was 28.2 and 35.3 years and average body mass index was 26.4 and 32.4 kg/m2, respectively. Ventral hernia size was reduced with the first trans-abdominal wall traction insertion from 610.5 cm2 to 274.6 cm2 in the acute setting and from 598 cm2 to 236.9 cm2 in the chronic setting. Average time from damage-control laparotomy to device insertion was 12.9 days in the acute group and more than 3 years in the chronic group. Lost domain was achieved with an average of less than 2.5 trans-abdominal wall traction tightenings, correlating to 9.2 and 8.2 days in the acute and chronic groups, respectively. Enterocutaneous fistula occurrence was 9 percent in the acute group and 0 percent in the chronic group. CONCLUSIONS: All patients were successfully closed after reestablishment of the lost domain. Trans-abdominal wall traction is an effective means of reestablishing abdominal domain and achieving primary abdominal wall closure in all patients with giant ventral defects, both acute and chronic.

Not so fast to skin graft: transabdominal wall traction closes most "domain loss" abdomens in the acute setting.

BACKGROUND: Damage-control laparotomy (DCL) has revolutionized the surgery of injury. However, this has led to the dilemma of the nonclosable abdomen. Subsequently, there exists a subgroup of patients who after resuscitation and diuresis, remain nonclosable. Before the adoption of our open abdomen protocol (OAP) and use of transabdominal wall traction (TAWT), these patients required skin grafting and a planned ventral hernia. We hypothesize that our OAP and TAWT device, which use full abdominal wall thickness sutures to dynamically distribute midline traction, achieve an improved method of fascial reapproximation. METHODS: From 2008 to 2011, all DCL and decompressive laparotomy patients in our urban trauma center were managed by our OAP. Thirty two were noncloseable "domain loss abdomens" after achieving physiologic steady state and near dry weight. All patients received the TAWT device when near dry weight was achieved. Wound size, days to closure, days to TAWT, and TAWT to closure were tracked. RESULTS: During this 36-month period, OAP/TAWT was applied to 32 patients. All patients demonstrated domain loss precluding fascial closure. Average wound size was 18.5-cm width by 30.5-cm length. Mean time DCL surgery to TAWT was 9.5 days. At time of placement, TAWT decreased initial wound width by an average of 9.8 cm (51.4%). Patients returned to the operating room for tightening/washout an average of 2.2 times (excluding TAWT insertion and final closure operations). Mean time TAWT to closure was 8.7 days. Mean time from admission surgery to primary closure was 18.2 days. All patients achieved primary fascial closure using this method without components separation or biologic bridge operations. CONCLUSION: OAP/TAWT has revolutionized the way we manage "domain loss" open abdomen patients and has virtually eliminated the acceptance of planned ventral hernia. TAWT consistently recaptures lost domain, preserves the leading fascial edge, and eliminates the need for biologic bridges, components separation, or skin grafting. LEVEL OF EVIDENCE: Therapeutic study, level III.