Roux-en-Y gastric bypass alters intestinal glucose transport in the obese Zucker rat.

Introduction: The gastrointestinal tract plays a major role in regulating glucose homeostasis and gut endocrine function. The current study examines the effects of Roux-en-Y gastric bypass (RYGB) on intestinal GLP-1, glucose transporter expression and function in the obese Zucker rat (ZR). Methods: Two groups of ZRs were studied: RYGB and sham surgery pair-fed (PF) fed rats. Body weight and food intake were measured daily. On post-operative day (POD) 21, an oral glucose test (OGT) was performed, basal and 30-minute plasma, portal venous glucose and glucagon-like peptide-1 (GLP-1) levels were measured. In separate ZRs, the biliopancreatic, Roux limb (Roux) and common channel (CC) intestinal segments were harvested on POD 21. Results: Body weight was decreased in the RYGB group. Basal and 30-minute OGT plasma and portal glucose levels were decreased after RYGB. Basal plasma GLP-1 levels were similar, while a 4.5-fold increase in GLP-1 level was observed in 30-minute after RYGB (vs. PF). The increase in basal and 30-minute portal venous GLP-1 levels after RYGB were accompanied by increased mRNA expressions of proglucagon and PC 1/3, GPR119 protein in the Roux and CC segments. mRNA and protein levels of FFAR2/3 were increased in Roux segment. RYGB decreased brush border glucose transport, transporter proteins (SGLT1 and GLUT2) and mRNA levels of Tas1R1/Tas1R3 and α-gustducin in the Roux and CC segments. Conclusions: Reductions in intestinal glucose transport and enhanced post-prandial GLP-1 release were associated with increases in GRP119 and FFAR2/3 after RYGB in the ZR model. Post-RYGB reductions in the regulation of intestinal glucose transport and L cell receptors regulating GLP-1 secretion represent potential mechanisms for improved glycemic control.

Evolving Antibiotic Resistance of Aeromonas Species in Finger Replantation.

Background: Infections with Aeromonas spp. are a recognized complication of leech therapy for circulatory complications in replanted digits. Ciprofloxacin is commonly used empirically for Aeromonas coverage in such cases. Evolving resistance patterns of Aeromonas should be considered in designing an antibiotic strategy. Methods: Three consecutive patients with complicated replantations had site cultures yielding Aeromonas isolates resistant to ciprofloxacin. These cultures were analyzed to identify effective antibiotic agents. Results: Each Aeromonas isolate, and each additional site organism, was sensitive to cefepime. Conclusion: Our routine antibiotic coverage for leech application has been changed to cefepime. Aeromonas sensitivities and resistances should be monitored to adapt to future changes in appropriate antibiotics.

Coronary Vasospasm After Burn Injury: First Described Case Series of a Lethal Lesion.

Burn injuries generate multisystem physiological derangements. The authors present a case series of three patients developing acute coronary syndrome (ACS) stemming from coronary vasospasm (CVS) over a course of 5 months. This etiology of ACS is significant as it has previously not been described in burn patients and requires a different management algorithm than vaso-occlusive disease.All patients were admitted to a single accredited burn unit. Burn mechanisms were flash burn, chemical fire, and house fire. TBSA were 20%, 72%, and 31%, respectively. Ages were 67-, 41-, and 52-year-old men. All smoked tobacco, and one had diabetes and coronary artery disease. CVS presented with acute onset ST elevations, severe bradycardia, and cardiac arrest in all. Diagnosis was made via EKG and angiography. Treatment was undertaken with nitrates and calcium channel blockers. One of the patients died of refractory disease.The authors identified CVS in burn patients with an incidence of 2% of admissions and accounting for 17% of our burn mortality during this period. To date, there is no linkage between CVS and burns described in humans; however, there is a well-described animal model in rats. The risk factors for CVS are common among burn patients, particularly smoking and endothelial dysfunction. CVS may be a significant cause of ACS in burn patients, and it should be considered in the setting of ACS especially with a negative angiography. Knowledge of this disease state can change burn management to mitigate risk and accommodate specific cardiac treatments.

The First Year of Global Cleft Surgery Education Through Digital Simulation: A Proof of Concept.

INTRODUCTION: Parallel to worldwide disparities in patient access to health care, the operative opportunities of surgical trainees are increasingly restricted across the globe. Efforts have been directed toward enhancing surgical education outside the operating room and reducing the wide variability in global trainee operative experience. However, high costs and other logistical concerns may limit the reproducibility and sustainability of nonoperative surgical education resources. METHODS: A partnership between the academic, nonprofit, and industry sectors resulted in the development of an online virtual surgical simulator for cleft repair. First year global access patterns were observed. RESULTS: The simulator is freely accessible online and includes 5 normal and pathologic anatomy modules, 5 modules demonstrating surgical markings, and 7 step-by-step procedural modules. Procedural modules include high-definition intraoperative footage to supplement the virtual animation in addition to include multiple-choice test questions. In its first year, the simulator was accessed by 849 novel users from 78 countries; 70% of users accessed the simulator from a developing nation. CONCLUSION: The Internet shows promise as a platform for surgical education and may help address restrictions and reduce disparities in surgical training. The virtual surgical simulator presented may serve as the foundation for the development of a global curriculum in cleft repair.

Carbon Monoxide and Cyanide Poisoning in the Burned Pregnant Patient: An Indication for Hyperbaric Oxygen Therapy.

Carbon monoxide (CO) is a small molecule poison released as a product of incomplete combustion. Carbon monoxide binds hemoglobin, reducing oxygen delivery. This effect is exacerbated in the burned pregnant patient by fetal hemoglobin that binds CO 2.5- to 3-fold stronger than maternal hemoglobin. With no signature clinical symptom, diagnosis depends on patient injury history, elevated carboxyhemoglobin levels, and alterations in mental status. The standard of care for treatment of CO intoxication is 100% normobaric oxygen, which decreases the half-life of CO in the bloodstream from 5 hours to 1 hour. Hyperbaric oxygen (HBO2) is a useful adjunct to rapidly reduce the half-life of CO to 20 minutes and the incidence of delayed neurologic sequelae. Because of the slow disassociation of CO from hemoglobin in the fetus, there is a far stronger indication for HBO2 in the burned pregnant patient than in other burn patient populations.Cyanide intoxication is often a comorbid disease with CO in inhalation injury from an enclosed fire, but may be the predominant toxin. It acts synergistically with CO to effectively lower the lethal doses of both cyanide and CO. Diagnosis is best made in the presence of high lactate levels, carboxyhemoglobin concentrations greater than 10%, injury history of smoke inhalation from an enclosed fire, and alterations in consciousness. While treatment with hydroxocobalamin is the standard of care and has the effect of reducing concomitant CO toxicity, data indicate cyanide may also be displaced by HBO2.Carbon monoxide and cyanide poisoning presents potential complications impacting care. This review addresses the mechanism of action, presentation, diagnosis, and treatment of CO and cyanide poisonings in the burned pregnant patient and the use of HBO2 therapy.

Fifty Years of Burn Care at Shriners Hospitals for Children, Galveston.

More than 50 years ago, Shriners Hospitals for Children expanded their philanthropy to include care for burned children. In so doing, the effects of their work weightily expanded from rehabilitation and quality of life outcomes to include survival proper. As the first facility dedicated to the care of burned children, originally designated the Shriners Burn Institute, the Galveston hospital remains the cornerstone of this endeavor. Shriners maintains charitable pediatric hospitals, provide care irrespective of the patient's or the family's ability to pay, and promote research. The sole criterion for admission at Shriners Hospitals for Children is the determination by a surgeon at a Shriners hospital that "the child's trouble may be corrected or improved." This philanthropic effort to provide medical care for children is one expression of the human commonality recognized by Shriners. In this article, we provide some background information on how this hospital came into existence as well as a global summary of its interventions toward greater survival and more complete rehabilitation of burned children. Based on the findings presented herein, we assert that there is less suffering and less loss of life due to childhood burns today than in previous years. We attribute much of this improvement to the simple voluntary collective decision by Shriners to provide alms for burned children.

Volume Resuscitation in Patients With High-Voltage Electrical Injuries.

Volume resuscitation of patients with high-voltage electrical injuries (>1000 V) is a more complex challenge than standard burn resuscitation. High voltages penetrate deep tissues. These deep injuries are not accounted for in resuscitation formulae dependent on percentage of cutaneous burn. Myonecrosis occurring from direct electrical injury and secondary compartment syndromes can result in rhabdomyolysis, compromising renal function and urine output. Urine output is the primary end point, with a goal of 1 mL/kg/h for adult patients with high-voltage electrical injuries. As such, secondary resuscitation end points of laboratory values, such as lactate, base deficit, hemoglobin, and creatinine, as well as hemodynamic monitoring, such as mean arterial pressure and thermodilution techniques, can become crucial in guiding optimum administration of resuscitation fluids. Mannitol and bicarbonates are available but have limited support in the literature. High-voltage electrical injury patients often develop acute kidney injury requiring dialysis and have increased risks of chronic kidney disease and mortality. Continuous venovenous hemofiltration is a well-supported adjunct to clear the myoglobin load that hemodialysis cannot from circulation.

Inhalation Injury in the Burned Patient.

Inhalation injury causes a heterogeneous cascade of insults that increase morbidity and mortality among the burn population. Despite major advancements in burn care for the past several decades, there remains a significant burden of disease attributable to inhalation injury. For this reason, effort has been devoted to finding new therapeutic approaches to improve outcomes for patients who sustain inhalation injuries.The three major injury classes are the following: supraglottic, subglottic, and systemic. Treatment options for these three subtypes differ based on the pathophysiologic changes that each one elicits.Currently, no consensus exists for diagnosis or grading of the injury, and there are large variations in treatment worldwide, ranging from observation and conservative management to advanced therapies with nebulization of different pharmacologic agents.The main pathophysiologic change after a subglottic inhalation injury is an increase in the bronchial blood flow. An induced mucosal hyperemia leads to edema, increases mucus secretion and plasma transudation into the airways, disables the mucociliary escalator, and inactivates hypoxic vasocontriction. Collectively, these insults potentiate airway obstruction with casts formed from epithelial debris, fibrin clots, and inspissated mucus, resulting in impaired ventilation. Prompt bronchoscopic diagnosis and multimodal treatment improve outcomes. Despite the lack of globally accepted standard treatments, data exist to support the use of bronchoscopy and suctioning to remove debris, nebulized heparin for fibrin casts, nebulized N-acetylcysteine for mucus casts, and bronchodilators.Systemic effects of inhalation injury occur both indirectly from hypoxia or hypercapnia resulting from loss of pulmonary function and systemic effects of proinflammatory cytokines, as well as directly from metabolic poisons such as carbon monoxide and cyanide. Both present with nonspecific clinical symptoms including cardiovascular collapse. Carbon monoxide intoxication should be treated with oxygen and cyanide with hydroxocobalamin.Inhalation injury remains a great challenge for clinicians and an area of opportunity for scientists. Management of this concomitant injury lags behind other aspects of burn care. More clinical research is required to improve the outcome of inhalation injury.The goal of this review is to comprehensively summarize the diagnoses, treatment options, and current research.

Topical Antimicrobials in Burn Care: Part 1-Topical Antiseptics.

Burn wounds disrupt the body's primary defense against invasion and colonization by microorganisms. Topical antimicrobials are one component in burn wound care. These agents suppress microbial growth to advantage skin cells and wound healing. Topical antimicrobials can be divided into 2 superclasses: antiseptics and antibiotics. We review the 4 main classes of topical antiseptics (emulsifiers, acids, oxidizers, and heavy metals) and antiseptic-impregnated dressings in current clinical use and address the mechanisms, as well as the advantages and disadvantages of each antiseptic for burn wound management.

Temporary ectopic implantation for salvaging amputated parts: A systematic review.

BACKGROUND: Temporary ectopic implantation is an option when handling severe crushing injuries to the distal extremities or other body parts. The surgical techniques applied in those cases, and the patient outcomes have not been previously analyzed. METHODS: Extensive literature search was performed using PubMed, EMBASE, and Google Scholar to collect articles reporting outcomes of temporary ectopic implantation for salvaging amputated extremities or other body parts. Age and sex of patients, injured part, amputation level, surgical details, and clinical outcomes were recorded. RESULTS: Twenty-two articles encompassing 38 amputated cases met the inclusion criteria. The publication dates ranged from 1986 to 2016. Of the 38 cases, temporary ectopic implantation procedures were performed in 16 digit cases, 10 hand cases, 3 forearm cases, 5 foot cases, 1 penis case, 1 testes case, and 2 scalp cases. The ectopic implantation duration varied from 6 to 319 days. The ectopic implantation and following replantation of the amputated parts resulted in a survival rate of 81.6% and 100%, respectively. With different follow-up durations, most patients were found to have sensation restore in the tips of reconstructed extremities, and those reconstructed extremities were functionally useful in daily lives. The function of other replanted parts was also satisfactory. CONCLUSION: Temporary ectopic implantation is a valuable technique for salvaging amputation cases resulted from severe crushing injuries. There is yet no consensus on the indications of this surgical technique. In future practices, both success and failure cases should be recorded and analyzed to help us to optimize the surgical strategies and improve the patient outcomes. LEVEL OF EVIDENCE: Systematic review, level IV.

Rapid Communication: Solution for the MEEK Glue Transfer Problem.

Meek micrografting permits wide expansion of skin grafts in true ratios from 3:1 to 9:1, as well as the utilization of poor donor sites. The proprietary glue critical to successful skin transference is unavailable in the United States. While the technique is widely employed worldwide, alternative glues resulted in poor skin transfer and frustrated use in American burn centers. The authors present their protocol resulting in effective MEEK skin transfer using Mastisol® adhesive: "The Rule of Sevens." 1) Soak the corks in normal saline for 7 minutes. 2) Then spread the grafts on the corks and mince with the MEEK machine. 3) Spray the epidermal surface of the micrograft-covered corks thoroughly with 7 pumps of Mastisol® from a distance of 7 inches (17.7 cm). 4) Allow the Mastisol® to dry for 7 minutes on the micrografts. 5) Apply the corks with the Mastisol®-imbued skin to the gauzes. Press firmly for 7 seconds. 6) Allow the skin to transfer from cork to gauze undisturbed for 7 minutes. Next, carefully remove the corks and expand the gauzes. Apply the micrograft-covered gauzes to excised and prepared wound beds and staple into position. 7) After 7 days, remove the gauzes, though the authors have left them in place for up to 21 days. This novel protocol provides reliable skin transfer and permits the modified MEEK technique to be a consistent part of our practice. The authors present this rapid communication to allow others to utilize this technique without the frustration of adhesive failure resulting in lost grafts.

Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat.

The hindgut hypothesis posits improvements in Type 2 diabetes after gastric bypass surgery are due to enhanced delivery of undigested nutrients to the ileum, which increase incretin production and insulin sensitivity. The present study investigates the effect of ileal interposition (IT), surgically relocating a segment of distal ileum to the proximal jejunum, on glucose tolerance, insulin sensitivity, and glucose transport in the obese Zucker rat. Two groups of obese Zucker rats were studied: IT and sham surgery ad libitum fed (controls). Changes in food intake, body weight and composition, glucose tolerance, insulin sensitivity and tissue glucose uptake, and insulin signaling as well as plasma concentrations of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide were measured. The IT procedure did not significantly alter food intake, body weight, or composition. Obese Zucker rats demonstrated improved glucose tolerance 3 wk after IT compared with the control group (P < 0.05). Euglycemic, hyperinsulinemic clamp and 1-[(14)C]-2-deoxyglucose tracer studies indicate that IT improves whole body glucose disposal, insulin-stimulated glucose uptake, and the ratio of phospho- to total Akt (P < 0.01 vs. control) in striated muscle. After oral glucose, the plasma concentration of glucagon-like peptide-1 was increased, whereas GIP was decreased following IT. Enhanced nutrient delivery to the ileum after IT improves glucose tolerance, insulin sensitivity and muscle glucose uptake without altering food intake, body weight, or composition. These findings support the concept that anatomic and endocrine alterations in gut function play a role in the improvements in glucose homeostasis after the IT procedure.

Percutaneous retrieval of a biliary stent after migration and ileal perforation.

We present a case of a migrated biliary stent that resulted in a distal small bowel perforation, abscess formation and high grade partial small bowel obstruction in a medically stable patient without signs of sepsis or diffuse peritonitis. We performed a percutaneous drainage of the abscess followed by percutaneous retrieval of the stent. The entero-peritoneal fistula closed spontaneously with a drain in place. We conclude, migrated biliary stents associated with perforation distal to the Ligament of Trietz (LOT), may be treated by percutaneous drainage of the abscess and retrieval of the stent from the peritoneal cavity, even when associated with a large intra-abdominal abscess.

Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat.

OBJECTIVE: Obesity-related diabetes is caused by insulin resistance and beta-cell dysfunction. The current study examines changes in food intake, weight loss, body fat depots, oxygen consumption, insulin sensitivity, and incretin levels as potential mechanisms for improved glucose tolerance after Roux-en-Y gastric bypass (RYGB). METHODS: Three groups of genetically obese Zucker rats were studied: RYGB, sham surgery pair-fed (PF), and sham surgery ad libitum (AL) fed rats. Changes in body weight, visceral and subcutaneous fat depots, oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide, and peptide YY (PYY) were measured. RESULTS: Body weight and subcutaneous fat were decreased after RYGB, compared with the PF and AL groups. The reduction in visceral fat after RYGB appeared largely because of food restriction. Glucose tolerance and insulin sensitivity were significantly improved in only the RYGB group (P < 0.05 vs. AL, PF). Euglycemic, hyperinsulinemic clamp studies indicated RYGB improved the ability of insulin to stimulate peripheral (eg, skeletal muscle) glucose uptake. Fasting total GLP-1, glucose-dependent insulinotropic peptide, and PYY levels were similar between the groups, whereas postprandial plasma levels of intact GLP-1 (7-36) amide, total GLP-1, and PYY were increased in the RYGB group compared with PF and AL controls. CONCLUSIONS: Glucose homeostasis after RYGB is associated with decreased subcutaneous fat, increased postprandial PYY, GLP-1, and insulin, as well as improved insulin sensitivity/action. Changes in food intake and visceral fat do not seem to explain improvements in insulin action after RYGB in the Zucker rat model.

Apolipoprotein A-IV, a putative satiety/antiatherogenic factor, rises after gastric bypass.

Roux-en-Y gastric bypass surgery (RYGBP) leads to improvements in satiety and obesity-related comorbidities. The mechanism(s) underlying these improvements are not known but may be revealed in part by discovery proteomics. Therefore, fasting plasma was collected from 12 subjects (mean BMI >45) during RYGBP and during a second procedure approximately 17 months later. Body weight, obesity-related comorbidities, and medication use were decreased after RYGBP. Mass spectrometry-based proteomic analysis was performed on a subset of seven samples using isobaric isotope-coded affinity tags (four plex iTRAQ). Initial proteomic analysis (n = 7) quantified and identified hundreds of plasma proteins. Manual inspection of the data revealed a 2.6 +/- 0.5-fold increase in apolipoprotein A-IV (apo A-IV, gene designation: APOA4), a approximately 46-kDa glycoprotein synthesized mainly in the bypassed small bowel and liver after RYGBP. The change in apo A-IV was significantly greater than other apolipoproteins. Immunoblot analysis of the full longitudinal sample set (n = 12) indicated even higher increases (8.3 +/- 0.2 fold) in apo A-IV. Thus iTRAQ may underestimate the changes in protein concentrations compared to western blotting of apo A-IV. Apo A-IV inhibits gastric emptying and serves as a satiety factor whose synthesis and secretion are increased by the ingestion of dietary fat. It also possesses anti-inflammatory and antiatherogenic properties. Based on these functions, we speculate changes in apo A-IV may contribute to weight loss as well as the improvements in inflammation and cardiovascular disease after RYGBP. In addition, the findings provide evidence validating the use of iTRAQ proteomics in discovery-based studies of post-RYGBP improvements in obesity-related medical comorbidities.

Genotypic alteration of HAART-persistent HIV-1 reservoirs in vivo.

Three HIV-1-infected individuals, on virally-suppressive highly active anti-retroviral therapy (HAART), were treated in vivo with anti-retroviral inhibitor intensification and cell stimulatory therapies in attempting to eradicate latent viral reservoirs. Afterwards, the patients ceased all anti-retroviral drugs. Sequences of the V3 region of HIV-1 envelope protein (ENV) from patient peripheral blood mononuclear cell (PBMC) proviral DNA, patient blood plasma viral RNA and virion-associated RNA from viruses amplified by patient cell co-culture, were obtained before, during, and certain times after the clinical regimen. As anticipated, the V3 loop sequencing results indicate diversity in viral strain complexity among the individual patients. However, the detection of unique V3 ENV signature sequences or V3 signatures of low frequency, relative to those observed prior to therapy, indicate that the expression of specific viruses, or viruses of low abundance, can be induced through stimulation in vivo. Furthermore, this stimulation or general immune activation therapy (IAT) approach, consisting of administration of the anti-T-cell receptor antibody, OKT3, and IL-2 in vivo, appeared to have subsequently altered the genotype of the persistent viral reservoir in peripheral blood cells for two of the three patients.

Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells.

Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics.