Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis.

BACKGROUND: Infectious complications following experimental pancreatitis involve major disruptions in the gut microbiota. The aim of this study was to characterize this disruption by examining the spatioregional distribution in microbial community structure and function following experimental pancreatitis associated with pancreatic infection. METHODS: Mice were subjected to infusion of the pancreatic duct with either taurocholate to induce necrotizing pancreatitis or normal saline (control group). The spatial (lumen versus mucosa) and regional composition and function of the microbiota from the duodenum, ileum, caecum, colon, pancreas and blood were evaluated using 16S rRNA gene amplicon sequencing. RESULTS: Mice that developed necrotizing pancreatitis demonstrated a decrease in microbial richness and significantly altered microbiota in distal parts of the gastrointestinal tract, compared with controls. Among the most differentially increased taxa were the mucus-degrading Akkermansia muciniphila, and there was a decrease of butyrate-producing bacteria following pancreatitis. Application of the SourceTracker tool to the generated metadata indicated that the duodenum was the most probable source of bacteria that subsequently infected pancreatic tissue in this model. The functional prediction annotation using pathway analyses indicated a diminished capacity of the caecal microbiota to metabolize carbohydrate, and fatty and amino acids. DISCUSSION: The distal gut microbiota was significantly impacted in this model of experimental necrotizing pancreatitis. Data suggest that the duodenal microbiota might also play a role in bacterial translation and secondary infections.

Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model.

BACKGROUND: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. METHODS: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. RESULTS: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65-90 per cent for WD versus 4-15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). CONCLUSION: The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice. Surgical relevance Worldwide, enhanced recovery programmes have developed into standards of care that reduce major complications after surgery, such as surgical-site infections and anastomotic leak. A complementary effort termed prehabilitation includes preoperative approaches such as smoking cessation, exercise and dietary modification. This study investigated whether a short course of dietary prehabilitation in the form of a low-fat/high-fibre composition can reverse the adverse effect of a high-fat Western-type diet on anastomotic healing in mice. Intake of a Western-type diet had a major adverse effect on both the intestinal microbiome and anastomotic healing following colonic anastomosis in mice. This could be reversed when mice received a low-fat/high-fibre diet before operation. Taken together, these data suggest that dietary modifications before major surgery can improve surgical outcomes via their effects on the intestinal microbiome.

ANTECEDENTES: Tanto la obesidad como la presencia de cepas bacterianas colagenolíticas (Enterococcus faecalis) pueden aumentar el riesgo de fuga anastomótica. El objetivo de este estudio fue determinar si los ratones alimentados durante un tiempo prolongado con una dieta de tipo occidental con alto contenido en grasas (western type diet, WD) desarrollaban una fuga anastomótica en asociación con una microbiota alterada, así como determinar si una dieta estándar preoperatoria de corta duración baja en grasa/alta en fibra (standard diet, SD) podía mitigar la aparición de fuga. MÉTODOS: Ratones machos C57BL/6 obtenidos de Charles River fueron asignados aleatoriamente a una dieta chow estándar (SD) o a una dieta de tipo occidental obesogénica (WD) durante 6 semanas, seguida de la administración preoperatoria de antibióticos y la realización de una anastomosis en el colon. La microbiota se analizó longitudinalmente después de la operación y se correlacionó con la curación utilizando una puntuación de cicatrización anastomótica ya establecida. En experimentos repetidos, los ratones con una WD durante 6 semanas fueron expuestos a una SD durante 2, 4 y 6 días antes de la cirugía de colon, analizándose la cicatrización de la anastomosis y la microbiota del colon. RESULTADOS: Los ratones alimentados con WD en comparación con los alimentados con SD presentaron un mayor riesgo de fuga anastomótica con un rápido incremento en la abundancia de Enterococcus (65-90% para WD versus 4-15% para SD, P < 0,01). La microbiota de ratones alimentados con SD, pero no con WD, se restableció a su composición preoperatoria después de la operación. La cicatrización anastomótica mejoró significativamente cuando los ratones alimentados con WD fueron expuestos a una dieta SD durante 2 días antes del tratamiento antibiótico y de la cirugía (P < 0,01). CONCLUSIÓN: En ratones, los efectos adversos de una alimentación crónica con una WD sobre la microbiota y la cicatrización anastomótica se pueden prevenir mediante una SD de corta duración.

Bowel preparation under siege.

An analysis of the results and conclusions from the most recent RCTs of the role of mechanical bowel preparation before colonic surgery is presented. The results indicate a wide disparity in the methods, results and conclusion of these studies, and the lack of microbial culture confirmation to advance understanding of how to move the field forward. Controversy on bowel preparation in colorectal surgery.

Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model.

BACKGROUND: Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues. METHODS: Polyphosphorylated polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA-PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed. RESULTS: Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA-PEG20k-Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6-4800-fold (P = 0·008; 5 animals). CONCLUSION: These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.

Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery.

BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery. METHODS: PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome', 'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'. RESULTS: There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself. CONCLUSION: Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

The gut microbiome and the mechanism of surgical infection.

BACKGROUND: Since the very early days of surgical practice, surgeons have recognized the importance of considering that intestinal microbes might have a profound influence on recovery from surgical diseases such as appendicitis and peritonitis. Although the pathogenesis of surgical diseases such as cholelithiasis, diverticulosis, peptic ulcer disease and cancer have been viewed as disorders of host biology, they are emerging as diseases highly influenced by their surrounding microbiota. METHODS: This is a review of evolving concepts in microbiome sciences across a variety of surgical diseases and disorders, with a focus on disease aetiology and treatment options. RESULTS: The discovery that peptic ulcer disease and, in some instances, gastric cancer can now be considered as infectious diseases means that to advance surgical practice humans need to be viewed as superorganisms, consisting of both host and microbial genes. Applying this line of reasoning to the ever-ageing population of patients demands a more complete understanding of the effects of modern-day stressors on both the host metabolome and microbiome. CONCLUSION: Despite major advances in perioperative care, surgeons today are witnessing rising infection-related complications following elective surgery. Many of these infections are caused by resistant and virulent micro-organisms that have emerged as a result of human progress, including global travel, antibiotic exposure, crowded urban conditions, and the application of invasive and prolonged medical and surgical treatment. A more complete understanding of the role of the microbiome in surgical disease is warranted to inform the path forward for prevention.

Diet creates metabolic niches in the "immature gut" that shape microbial communities.

Although diet composition has been implicated as a major factor in the etiology of various gastrointestinal diseases, conclusive evidence remains elusive. This is particularly true in diseases such as necrotizing enterocolitis where breast milk as opposed to commercial formula appears to confer a "protective effect" to the "immature gut." Yet the mechanism by which this occurs continues to remain speculative. In the present study we hypothesize that the basic chemical composition of diet fundamentally selects for specific intestinal microbiota which may help explain disparate disease outcome and therapeutic direction. Complimentary animal and human studies were conducted on young piglets (21 d.)(n = 8) (IACUC protocols 08070 and 08015) and premature infants (adjusted gestational age 34-36 weeks) (n = 11) (IRB Protocol 15895A). In each study, cecal or stool contents from two groups (Breast milk-fed (BF) vs. Formula-fed (FF)) were analyzed by gas chromatography/mass spectrometry (GC/MS) and comprehensive metabolic profiles generated and compared. Concurrently, bacterial community structure was assayed and respective representative microbiota of the groups determined by 16S rRNA gene amplicon pyrosequencing. Statistical modeling and analysis was done using SIMCA-P+ and R software. GC/MS metabolomics identified clear differences between BF and FF groups in the intestinal environment of piglets and humans. Sugars, amino-sugars, fatty acids, especially unsaturated fatty acids, and sterols were identified as being among the most important metabolites for distinguishing between BF and FF groups. Joint analysis of microbiota and metabolomics pinpointed specific sets of metabolites (p < 0.05) associated with the dominant bacterial taxa. The chemical composition of diet appears to have a significant role in defining the microbiota of the immature gut. Tandem analysis of intestinal microbial and metabolic profiles is potentially a powerful tool leading to better understanding of the role of diet in disease perhaps even leading to specific strategies to alter microbial behavior to improve clinical outcome.

The key role of Pseudomonas aeruginosa PA-I lectin on experimental gut-derived sepsis.

OBJECTIVE: To examine the effect of Pseudomonas aeruginosa on intestinal barrier function and its lethal potential when introduced into the intestinal tract of mice. SUMMARY BACKGROUND DATA: The mere presence of P. aeruginosa in the intestinal tract of critically ill patients is associated with a threefold increase in death compared with matched cohorts without this pathogen. Whether this effect is a cause or a consequence of the critically ill state has not been previously addressed. METHODS: Transepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells apically inoculated with live P. aeruginosa, exotoxin A, or purified PA-I lectin, an adhesin of P. aeruginosa. Lethality studies to P. aeruginosa were carried out in mice undergoing 30% surgical hepatectomy by injecting the bacteria or its various components directly into the cecum. RESULTS: Only cells exposed to P. aeruginosa or its PA-I lectin developed alterations in barrier function. P. aeruginosa or the combination of PA-I and exotoxin A was lethal to mice when injected into the cecum after partial hepatectomy. Alterations in epithelial barrier function and death in mice were prevented when Pseudomonas was pretreated with N-acetyl D-galactosamine (GalNAc), a binder of PA-I. CONCLUSIONS: P. aeruginosa may act as a pathogen in the gastrointestinal tract, resulting in altered epithelial barrier function and death in a susceptible host. The PA-I lectin of P. aeruginosa may play a key role in its pathogenicity to the intestinal epithelium by inducing a permeability defect to its cytotoxic exoproducts such as exotoxin A.

Surgical stress, bacteria, and mucosal immune function.

Bacteria share a benign coexistence with host mucosal surfaces in the gastrointestinal tract during periods of health. Both host epithelial defense function and bacterial virulence phenotypes are significantly affected by stress. Via discreet and specific sensory input signals to bacteria, the molecular machinery of otherwise commensal strains of bacteria can shift the phenotypes of residential colonizers to more virulent and invasive strains. This occurs at a time when the host may be relatively immunosuppressed by the injury. This adaptive response demonstrates the duplicitous nature of bacteria residing on mucosal surfaces whose ability to shift their virulence characteristics may play an important role in infectious-related morbidity following surgical stress.

Perturbed bioelectrical properties of the mouse cecum following hepatectomy and starvation: the role of bacterial adherence.

Previous work in our laboratory has demonstrated that bacterial adherence alone to the intestinal epithelium, as occurs following catabolic stress, significantly perturbs the normal electrophysiology of the cecal mucosa. The aim of this study was to further characterize these effects in the mouse cecum following hepatectomy and short-term starvation, and to define the role of bacterial adherence in this process. Groups of mice underwent a surgical hepatectomy and were either fed or starved during the postoperative period. Groups of controls underwent sham operations and were either fed or starved postoperatively. Electrophysiologic studies in Ussing chambers at 48 hours were performed. Bacterial adherence to the mucosa was assessed by culture and histologic staining. To determine the role of bacteria in the altered electrophysiologic response, ciprofloxacin decontamination studies were performed. Only mice subjected to both hepatectomy and starvation developed bacterial adherence of sufficient magnitude (>10(5) cfu/gm) to alter mucosal electrophysiology (short-circuit current and basal potential difference). Ciprofloxacin decontamination completely abrogated this effect. Ion replacement studies suggested that active sodium transport was primarily responsible for the observed changes in mucosal electrophysiology. Bacterial-epithelial cell interactions may be responsible for altered mucosal ion transport observed following operative catabolic stress and short-term starvation.

Increased type 1 fimbrial expression among commensal Escherichia coli isolates in the murine cecum following catabolic stress.

Although indigenous bacteria intimately colonize the intestinal mucosa, under normal conditions the intestinal epithelial cell is free of adherent bacteria. Nonetheless, commensal bacteria such as Escherichia coli adhere to and translocate across the intestinal epithelium in association with a number of pathologic states including hemorrhagic shock, immunosuppression, traumatic tissue injury, and lack of enteral feedings. The adhesins involved in the adherence of indigenous E. coli to the intestinal epithelium in vivo following catabolic stress are unknown. We have developed a mouse model to study the bacterial adhesins which mediate the increased intestinal adherence of E. coli after partial hepatectomy and short-term starvation. Our studies demonstrated that hepatectomy and starvation in the mouse were associated with a 7,500-fold increase in the numbers of E. coli bacteria adhering to the cecum. In addition, erythrocyte agglutination studies, as well as immunostaining of fimbrial preparations and electron micrographs of the bacteria, revealed that surface type 1 fimbriae were more abundant in the commensal E. coli harvested from the ceca of the stressed mice. These E. coli isolates adhered to a mouse colon cell line and injected cecal loops in a mannose-inhibitable manner, which suggests a role for type 1 fimbriae in the adherence of the E. coli isolates to the cecum in vivo following host catabolic stress.

Are physiological effects of sleep deprivation in the rat mediated by bacterial invasion?

Recent reports have indicated that rats subjected to total sleep deprivation (TSD) by the disk-over-water method and sacrificed when death appeared imminent showed aerobic bacteria in their blood. Yoked control rats did not. Extrapolating from these results, it has been suggested that the late body temperature declines and eventual deaths of TSD rats are caused by septicemia, and that other, earlier-appearing effects of TSD-including weight loss, increased energy expenditure, and regulation of temperature at a higher level-might be mediated by impaired host defenses against bacterial invasion. Three measures of aerobic bacterial invasion were used to evaluate these hypotheses: bacteremia, bacterial colonization in major organs of filtration (liver, kidney, and mesenteric lymph nodes), and adherence of bacteria to the cecal wall. Experiment 1 showed nonsignificant trends toward more bacterial invasion in 4-day TSD rats compared to yoked control rats and no relationship between the bacterial indicators and the early TSD effects. Experiment 2 showed that the elimination of aerobic bacterial infection by antibiotic treatment did not prevent the early TSD effects in 4-day TSD rats. Experiment 3 showed that the elimination of aerobic bacterial invasion in TSD rats did not eliminate the late temperature decline or the progression towards death. The results showed no significant evidence of aerobic bacterial invasion early in TSD and no indication that the major effects of TSD were dependent upon aerobic bacterial invasion.

Characteristics of the intestinal epithelial barrier during dietary manipulation and glucocorticoid stress.

OBJECTIVES: a) To determine the significance of stress-induced alterations in intestinal permeability by measuring the transmucosal flux of formyl-methionyl-leucyl-phenylalanine (f-MLP), a ubiquitous neutrophilic chemoattractant present in the human and rodent colon; and b) to determine whether stress and/or diet influence(s) bacterial adherence-induced changes in epithelial permeability by affecting the production of secretory immunoglobulin A (IgA), the main immune mechanism preventing bacterial adherence. DESIGN: Prospective, randomized, controlled study. SETTING: University animal research laboratory. SUBJECTS: Female Fischer rats. INTERVENTIONS: Rats were randomly assigned to four groups of seven animals each. Groups of animals were assigned to receive saline or dexamethasone (0.8 mg/kg ip) and were either starved (5% dextrose in water ad libitum) or fed (water and rat chow) for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Mucosal barrier function was evaluated by measuring secretory IgA, bacterial adherence to the intestinal mucosa, and transepithelial electrical resistance, a measure of tight junction permeability. The f-MLP permeation across the mucosa was also determined in segments with significant permeability changes. Results indicate that starvation in dexamethasone-treated rats significantly impairs secretory IgA, promotes bacterial adherence to the mucosa, and results in increased intestinal permeability to f-MLP. These effects are significantly attenuated by the feeding of rat chow. CONCLUSIONS: Alterations in intestinal barrier function are characterized by depressed IgA, bacterial adherence to the intestinal mucosa, and permeation of clinically relevant proinflammatory luminal macromolecules (f-MLP). Enteral stimulation with foodstuffs is a necessary protective measure to prevent altered epithelial barrier function during glucocorticoid stress.

Causes and consequences of bacterial adherence to mucosal epithelia during critical illness.

The interaction between host and pathogen during catabolic stress represents a dynamic battlefield, where the microbe's strategy to ensure its survival and multiplication come face to face with the repertoire of the host's immune system. From the microbe's point of view, the ICU offers the least optimal living condition, representing at times an outright holocaust for entire populations of fellow bacteria. This situation is especially true for intestinal bacteria, which can be exposed to all sorts of extreme conditions, such as starvation, turgor pressure, altered temperature, antibiotics, and osmolality changes. These conditions may act as environmental cues and elicit changes in bacterial gene expression that lead to effective coping responses. Starvation countermeasures can be especially strong signals for bacteria to follow chemical trails in search of nutrients. Harming the host is not the microbe's intent; its goal is to prevail. Injury to the host by a microbe struggling to survive is the inadvertent consequence of a threatening environment. This struggle between host and pathogen is particularly apparent at the mucosal surface, especially in the gastrointestinal tract, where microbes have enjoyed the leisurely life of a stable temperature and a constant food supply. The focus of this discussion is on one small aspect of the manner in which microbes ensure their survival during catabolic stress by attaching to host epithelial cells. The conditions and consequences of this process are discussed.

The effect of dexamethasone and endotoxin administration on biliary IgA and bacterial adherence.

Adherence of bacteria to the intestinal epithelial cell may be the crucial initiating event for invasion and translocation and is normally prevented by both immune (IgA) and nonimmune (mucus, peristalsis, desquamation) mucosal defense mechanisms. The purpose of the present study was to examine the effect of endotoxin administration on mucosal immunity and to define the role of glucocorticoids, commonly released during endotoxicosis, in this process. Thirty female Fisher rats were randomly assigned to three groups of 10 animals each. Group I (CONT), was fed rat chow and H2O ad lib., Group II (DEX) was administered 0.8 mg/kg subcutaneously of dexamethasone, and Group III (ETX) was given 1 mg/kg of endotoxin. Twenty-four hours later animals were sacrificed and mesenteric lymph nodes and vigorously washed stool-free ceca were collected and cultured. Bile was collected and assayed for IgA from 5 animals in each group. A significant decrease (P < 0.05) in secretory IgA was noted in animals treated with either dexamethasone or endotoxin (CONT = 332 +/- 42, DEX = 78 +/- 24, ETX = 68 +/- 16 micrograms/mg protein +/- SEM). No difference in S-IgA between animals in the dexamethasone-treated group and the endotoxin-treated group was noted (P = NS). A statistically significant increase (P < 0.001) in bacteria adherent to the cecal wall in both the dexamethasone-treated rats and the endotoxin-treated rats over that in = 7.5 +/- 0.8, CONT = 6.4 +/- 0.6 cfu/g(log10) +/- SD). Our results suggest that endotoxin or glucocorticoid administration results in significant bacterial adherence to the cecal mucosa and a decrease in IgA.(ABSTRACT TRUNCATED AT 250 WORDS)

Total parenteral nutrition: iatrogenic immunosuppression.

It may be necessary for future formulations of TPN to encompass functions other than mere provisions of nutrients. Although current solutions of TPN are well tolerated in most patients for short periods and remain an important adjunct to modern surgical therapy, these solutions have significant room for improvement. Designing the ideal artificial gut for the highly stressed patient may include reproduction of the neurological, endocrine, and immune responses that occur after the oral presentation of foodstuffs.

Hepatitis prevalence in trauma patients.

The risks of viral transmission from trauma patients is a continuing concern to those involved in their care. However, the prevalence of hepatitis (HPT) in trauma patients is poorly described. The purpose of this study is to evaluate the prevalence of HPT in trauma patients admitted to an urban trauma center. Two hundred sixty-four consecutive admissions to an urban Level I trauma center underwent serologic screening for HPT. Risk factors were assessed by direct patient questioning. Serologic evidence of HPT B was found in 19.7 per cent of patients. Intravenous (IV) drug abusers represented eight per cent of the study population; this group had a 67 per cent rate of seropositivity. Hepatitis A was not found in any patient. Antigenemia was found in 1.9 per cent of patients. It is concluded that HPT B seropositivity is common in trauma patients. IV drug abusers have particularly high prevalence of HPT. This high prevalence rate of HPT B serology poses a significant risk to those involved with the care of trauma patients. The authors suggest that specific protocols to avoid the transmission of viral disease should be mandatory in urban trauma centers.

Carotid-esophageal fistula following a penetrating neck injury: case report.

Carotid arterial injuries frequently are associated with injuries to adjacent structure of the neck, particularly the esophagus and trachea. Complications from these repairs are common and fistula formation is herein described between the carotid artery and esophageal repair.