Low Rate of Infectious Enterocolitis in Allogeneic Stem Cell Transplant Recipients with Acute Diarrhea: A Prospective Study by the GETH-TC.

Acute diarrhea is a common and debilitating complication in recipients of allogeneic hematopoietic stem cell transplantation (HCT). In this prospective, observational, and multicenter study we examined all episodes occurring in the first 6 months of 142 consecutive adult patients who underwent a reduced-intensity conditioning HCT in 10 Spanish tertiary university hospitals. Fifty-four patients (38%) developed a total of 75 acute diarrhea episodes. The median time from HCT to the first episode was 38 days (4-157). The main cause of enterocolitis was lower GI-aGVHD (38%), followed by infections (21%) and drug-related toxicity (8%). Causative infectious causes were identified in only 16/75 episodes (21%). C. difficile-related infection was the most common infectious agent with an incidence and recurrence of 13% and 2%, respectively. With a median follow-up for survivors of 32 months, the non-relapse mortality (NRM) and the overall survival (OS) at 1 year, were 20% (95% C.I.: 14-28%) and 69% (95% C.I.: 61-77%), respectively. Development of enterocolitis was not associated with higher NRM (p = 0.37) or worse OS (p = 0.9). This real-life study confirms that the diagnosis and management of acute diarrhea in the early stages after HCT is challenging. Nosocomial infections seem to be relatively uncommon, probably due to more rational use of antibiotics.

Hirschsprung's disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality.

PURPOSE: Down syndrome (DS) is the most frequent chromosomal abnormality associated with Hirschsprung's disease (HD). It has often been suggested that this association results in poorer outcomes with regard to postoperative complications, continence and mortality. On the other hand, the results after surgical treatment of HD in patients with DS are reportedly similar to those in cases with HD alone. The objective of this study was to determine the incidence of DS in cohorts with HD, and to compare pre-/postoperative complications, functional outcome and mortality between cohorts with and without coexisting DS. METHODS: A systematic literature-based search for relevant cohorts was conducted using multiple online databases. The number of DS cases in HD cohorts was recorded and data on pre-/postoperative complications, functional outcome and mortality were extracted. Pooled odds ratios with 95% confidence intervals were calculated using meta-analysis methodology. RESULTS: Sixty-one articles met defined inclusion criteria, comprising data from 16,497 patients with HD. The overall incidence of DS among them was 7.32%. Vice versa, the incidence of HD in 29,418 patients with DS was 2.62%. There were no significant differences regarding the male-to-female ratio between cohorts with and without coexisting DS (4:1 vs. 3:1 respectively; P = 0.5376). The rate of additional comorbidities was significantly higher in HD associated with DS (P < 0.0001). Recto-sigmoid HD was in both cohorts the most common type of HD (P = 0.8231). Long-segment HD was significantly more frequent in HD with coexisting DS (P = 0.0267), while total colonic aganglionosis occurred significantly more often in HD without DS (P = 0.0003). There were no significant differences in preoperative constipation/obstruction (P = 0.5967), but the rate of preoperative enterocolitis was significantly higher in HD associated with DS (P = 0.0486). Postoperative complications such as recurrent enterocolitis (P = 0.0112) and soiling (P = 0.0002) were significantly more frequent in HD with coexisting DS. Although not statistically significant, fecal incontinence (P = 0.1014) and persistent constipation (P = 0.1670) occurred more often after surgical treatment of HD with DS. The mortality rate was significantly higher in HD associated with DS (P < 0.0001). CONCLUSIONS: The association of HD with DS is well-recognized with an incidence of 7.32%. A large number of patients with DS continue to have persistent bowel dysfunction after surgical treatment of HD. Our data provide strong evidence that the coexistence of HD and DS is associated with higher rates of pre-/postoperative enterocolitis, poorer functional outcomes and increased mortality.

Recurrence of radiation enterocolitis within 1 year is predictive of 5-year mortality in surgical cases of radiation enterocolitis: our 18-year experience in a single center.

BACKGROUND: Pelvic irradiation is commonly used in the treatment of pelvic malignancies. Chronic radiation enterocolitis is the most serious complication resulting from such treatment, and it frequently requires surgery. The prognosis for patients after surgery remains ill-defined. We conducted a retrospective study to identify risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis. METHODS: From 1985 to 2009, a total of 89 patients were diagnosed as having chronic radiation enterocolitis in Taichung Veterans General Hospital. The chart records of 35 surgical and 54 nonsurgical patients were reviewed. A total of 21 candidate risk factors were selected from (1) those related to rapid disease progression (recurrence within 1 year, reoperation within 1 year, short latency), (2) those mentioned in published series (diabetes mellitus, history of smoking, history of abdominopelvic surgery), and (3) other risk factors that might adversely affect outcomes (older age, higher radiation dosage, longer latency period). Factors with p < 0.1 in univariate analysis were subjected to multivariate analysis to identify those that were independent risk factors. RESULTS: Surgical patients were significantly older (65.09 vs. 61.61 years, p = 0.011), had a longer latency period (17.08 vs. 8.09 months, p = 0.037), and were associated with a higher percentage of radiation uropathy (54.28 vs. 12.96%, p < 0.0001) than nonsurgical patients. There was no difference in radiation dosage between surgical and nonsurgical cases (p = 0.152). Recurrence of radiation enterocolitis within 1 year following surgery (p = 0.022), older age (p = 0.002), and uncured cancer (p = 0.001) were identified as independent risk factors for poor overall survival after surgery. All patients (100%) who had recurrent radiation enterocolitis within 1 year of surgery died within 5 years of recurrence. CONCLUSIONS: The surgical cases were older, had a longer latency period, and had a higher percentage of radiation uropathy .Recurrence of radiation enterocolitis within 1 year after surgery, older age, and uncured cancer were independent risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis.

Early-life gut dysbiosis linked to juvenile mortality in ostriches.

BACKGROUND: Imbalances in the gut microbial community (dysbiosis) of vertebrates have been associated with several gastrointestinal and autoimmune diseases. However, it is unclear which taxa are associated with gut dysbiosis, and if particular gut regions or specific time periods during ontogeny are more susceptible. We also know very little of this process in non-model organisms, despite an increasing realization of the general importance of gut microbiota for health. METHODS: Here, we examine the changes that occur in the microbiome during dysbiosis in different parts of the gastrointestinal tract in a long-lived bird with high juvenile mortality, the ostrich (Struthio camelus). We evaluated the 16S rRNA gene composition of the ileum, cecum, and colon of 68 individuals that died of suspected enterocolitis during the first 3 months of life (diseased individuals), and of 50 healthy individuals that were euthanized as age-matched controls. We combined these data with longitudinal environmental and fecal sampling to identify potential sources of pathogenic bacteria and to unravel at which stage of development dysbiosis-associated bacteria emerge. RESULTS: Diseased individuals had drastically lower microbial alpha diversity and differed substantially in their microbial beta diversity from control individuals in all three regions of the gastrointestinal tract. The clear relationship between low diversity and disease was consistent across all ages in the ileum, but decreased with age in the cecum and colon. Several taxa were associated with mortality (Enterobacteriaceae, Peptostreptococcaceae, Porphyromonadaceae, Clostridium), while others were associated with health (Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, Turicibacter, Roseburia). Environmental samples showed no evidence of dysbiosis-associated bacteria being present in either the food, water, or soil substrate. Instead, the repeated fecal sampling showed that pathobionts were already present shortly after hatching and proliferated in individuals with low microbial diversity, resulting in high mortality several weeks later. CONCLUSIONS: Identifying the origins of pathobionts in neonates and the factors that subsequently influence the establishment of diverse gut microbiota may be key to understanding dysbiosis and host development. Video Abstract.

Development and validation of a simple and robust model to predict 30-day mortality in patients with Clostridioides difficile-associated enterocolitis.

OBJECTIVE: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and associated with high morbidity and mortality. As current guidelines recommend treatment stratified for disease severity, this study aimed to identify predictors of 30-day mortality in order to develop a robust prediction model. DESIGN: This was a retrospective analysis of 207 inpatients with CDI who were treated at the Jena University Hospital between September 2011 and December 2015. In a training cohort (n=127), predictors of 30-day mortality were identified by receiver operating characteristics analysis and logistic regression. The derived model was validated in an independent cohort of 80 inpatients with CDI. RESULTS: Within 30 days, 35 (28%) patients in the training cohort died from any cause. C-reactive protein (CRP) of ≥121 mg/L (OR 3.80; 95% CI 1.64 to 7.80; p=0.003) and lower systolic blood pressure of ≤104 mm Hg (OR 3.73; 95% CI 1.63 to 8.53; p=0.002) at diagnosis as well as development of renal impairment (serum creatinine >1.5×baseline; OR 5.61; 95% CI 1.94 to 16.26; p=0.035) within the first 6 days were associated with 30-day mortality in univariate analysis. The use of these parameters enabled correct mortality prediction in 73% of cases on the day of diagnosis and in 76% at day 6. In the validation cohort, 30-day mortality was 18/80 (23%). Our model enabled a 73.7% correct prediction concerning 30-day mortality on day 6 after diagnosis of CDI. CONCLUSION: Hypotension and CRP elevation on the day of diagnosis as well as occurrence of kidney dysfunction during the first 6 days are suitable parameters to predict 30-day mortality in patients with CDI who need to be treated in the hospital.

IBD and IBD mimicking enterocolitis in children younger than 2 years of age.

Inflammatory bowel disease (IBD) is uncommon in children younger than 2 years of age. The criteria for differentiating IBD from other diseases with similar clinical presentation is unclear. We describe 16 patients who, between 1984 and 2004, received a histological diagnosis of IBD during the first two years of life. Six patients presented with histological Crohn's disease, eight with ulcerative colitis and two with indeterminate colitis. The median age at diagnosis was 125 days (range 1 day to 18 months) and the medium follow up was 89 months (range 65 days to 20 years). The disease appeared to be very severe: four children (25%) underwent total parenteral nutrition (TPN), two received colectomy (12.5%) and three patients died. Many of the patients required an aggressive, multidrug, immunosuppressive approach (azathioprine [AZA], Infliximab, thalidomide, cyclosporine A). One child presented with a hypogammaglobulinaemia without any specific immunodeficiency, while in the other patients, Wiskott-Aldrich syndrome (WAS) (4 cases) and chronic granulomatous disease (CGD) (2 cases) were identified. In 6/16 cases, allergic colitis was first considered; these cases initially underwent cow's milk protein-free diet as the only therapy before IBD was finally diagnosed. In conclusion, early IBD has a severe prognosis and often needs an aggressive therapeutic approach. Furthermore, an improper diagnosis of allergic colitis might cause an important diagnostic delay. Some severe immunodeficiencies, such as WAS and CGD, may represent a problem in terms of differential diagnosis and might be wrongly diagnosed as very early onset IBD.

Effects of caprylic acid and triacylglycerols of both caprylic and capric acid in rabbits experimentally infected with enteropathogenic Escherichia coli O103.

Eighty-eight rabbits weaned at the age of 35 days were divided into four groups. Rabbits of the first two groups were fed a granulated feed, free of antimicrobials. Rabbits of the 3rd and the 4th groups were fed the same diet, supplemented with caprylic acid at 5 g/kg, and with triacylglycerols (TAG) of caprylic and capric acid at 10 g/kg, respectively. Rabbits of the 2nd, 3rd and 4th groups were challenged orally with 10(9) cells of Escherichia coli of the O103 serogroup. Numbers of coliform bacteria in faeces of non-infected rabbits averaged 4.66 log(10)cfu/g. Six days after inoculation, caprylic acid and TAG of caprylic and capric acid decreased faecal output of coliforms from 10.18+/-0.62 to 7.79+/-0.48 log(10)cfu/g and 8.04+/-0.50 log(10)cfu/g, respectively. In the 2nd, 3rd and 4th groups 15, 11 and 9 infected rabbits died, respectively. However, the differences in mortality rate were not statistically significant. Surviving rabbits were slaughtered at 53 days of age. In caecal contents of infected rabbits, numbers of coliform bacteria were significantly reduced from 8.71 log(10)cfu/g to 5.55-5.83 log(10)cfu/g in treated groups. It can be concluded that both antimicrobial lipids are active against coliform bacteria, and may improve the resistance of weaned rabbits to enterocolitis.

Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography.

PURPOSE: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. PATIENTS AND METHODS: Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. RESULTS: Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean +/- SD, 10.2 +/- 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P <.0001), and the NE-related mortality rate was higher (29.5% v 0%, P <.001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness < or = 10 mm (4.2%, P <.001). CONCLUSION: Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.

Neutropenic enterocolitis in adults with acute leukemia.

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.

Management of Hirschsprung's disease in children with trisomy 21.

Thirteen infants and children with trisomy 21 have been treated for Hirschsprung's disease since 1975. Clinical presentation of Hirschsprung's disease included constipation (five); neonatal intestinal obstruction (four); enterocolitis (three); and meconium plug syndrome (one). Additional associated congenital anomalies occurred in 10 patients, of which complex cardiac disease accounted for 25% of the defects. Seven children underwent definitive operation: Duhamel pull-through (four); Soave pull-through (two); and anal myectomy (one). Satisfactory continence occurred in all but one child. Enterocolitis developed in seven patients (54%): two at diagnosis of Hirschsprung's disease; three after colostomy; and two after pull-through. Five children died (38%): one from enterocolitis, two from cardiorespiratory failure after recovery from enterocolitis, and two from end-stage cardiac disease. Children with trisomy 21 can safely undergo definitive operation for Hirschsprung's disease but are at high risk for developing enterocolitis and complications of associated cardiac disease.

Intestinal ischemia.

CONTEXT: As rejection in renal transplantation has become better controlled, gastrointestinal complications have become increasingly important. Ischemic colitis and colonic perforation are the most common of these lesions, contributing to morbidity and mortality in the early postoperative period. OBJECTIVE: We undertook this study to identify factors contributing to the risk of intestinal ischemia in patients undergoing renal transplantation and to define circumstances that may affect that risk. METHODS: We studied 356 patients undergoing renal transplantation during a 40-month period. We reviewed medical records, surgical pathology reports, autopsy reports, and pathology slides. RESULTS: Eleven (3.1%) of the patients developed ischemia of the small or large bowel or both within 20 days after transplantation, and 6 (54.5%) died as a result. Ten of these patients had received cadaveric kidneys and were older than 40 years. There was no sex predilection. The most common segment involved was the terminal ileum and ascending colon. We discuss possible reasons underlying these observations in this article. CONCLUSION: The mechanism behind posttransplantation intestinal ischemia is multifactorial, but regardless of etiology, it is important to emphasize the risk of intestinal ischemia in patients who develop abdominal symptoms during the early posttransplantation period, particularly in patients older than 40 years who have received cadaveric kidneys.

Intestinal perforations in infants with a very low birth weight: a disease of increasing survival?

Seventeen infants with a very low birth weight (VLBW) and spontaneous, non-necrotizing enterocolitis (NEC), intestinal perforations are presented; 14 of them were seen in the past 3 years. A comparison with 16 surgically treated NEC infants (< 1,000 g) is provided. At our institution, the yearly survival of VLBW infants increased from 54% to 90% over the past 6 years. All 17 non-NEC patients were operated on, and 15 (88.2%) survived. Ileal perforations were observed frequently. Initial enterostomies were followed by reanastomosis at an average age of 3 months. A 22.6-month follow-up was attained for all survivors. Non-NEC intestinal perforations in tiny neonates are increasing and constitute a challenging but treatable group. The improving survival rate of VLBW infants will probably be accompanied by a variety of complications.

Clinical risk factors of Hirschsprung-associated enterocolitis. I: Preoperative enterocolitis.

Enterocolitis is still the main source of mortality and morbidity in Hirschsprung's disease (HD). Between 1976 and 1993, 79 (26%) of 302 Hirschsprung patients proved to have Hirschsprung-associated enterocolitis (HAEC). Mortality was 7.6 percent (6 patients). HAEC patients, those who died of HAEC and those without HAEC were analyzed for differences in 34 parameters. The length of the aganglionic segment was found not to be a risk factor for HAEC, but early diagnosis and prompt treatment were found to decrease the occurrence of preoperative HAEC. Although we defined HAEC as foul-smelling, explosive diarrhea, some other symptoms and signs, such as abdominal distention on physical examination, vomiting, dehydration, and a history of nonspecific diarrhea were encountered with significant frequency. None of the patients had Down's syndrome. Sepsis was detected in all of the patients who died of HAEC. The severity of HAEC did not increase with the number of attacks of HAEC, and mortality was greater in the first three attacks. Differences in results between some series seemed to be related to differing definitions of HAEC.

[Clinical profile of cytomegalovirus (CMV) enterocolitis in acquired immunodeficiency syndrome]. / Perfil clínico da Enterocolite por Citomegalovírus (CMV) na síndrome da imunodeficiência adquirida (Aids).

OBJECTIVE: To determine the clinical profile of CMV colitis in AIDS patients, comparing clinical, endoscopic parameters and survival time between 2 groups of AIDS patients having chronic diarrhea. Group A being CMV colitis and group B without CMV colitis. METHODS: 48 patients with diarrhea that lasted more than 30 days, being 27 in Group A and 21 in Group B, were studied. Age, risk factors, interval time between the diagnosis of HIV infection and the beginning of diarrhea, hematochesia, the endoscopic findings and life table in both groups, were analysed. All of them were diagnosed by stool culture and stools for ovum and parasites, along colonoscopy with biopsies. The unpaired t test was used to assess statistical significance of differences observed in the means of continuous and the chi-square with Yates correction for non-parametric variables. The survival curves were assessed by the Kaplan-Meier and the Mantel-Haenszel's tests. A P value of less than 0,05 was considered to indicate statistical significance. RESULTS: The mucosal lesions associated with the CMV infection are typically ulcerative on a background of hemorrhagic erythema 14 (51,8%) p < 0,01. The life table analysis disclosed shorter survival time in the CMV colitis group 0,005> P>0,001. The others studied data did not achieve statistical significance. CONCLUSIONS: AIDS patients with CMV colitis have a poorer long-term survival. Among the colonoscopic findings, ulcerations with hemorrhagic background were the most common lesions.

Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.

BACKGROUND: Melanin-concentrating hormone (MCH), an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD). Expression of MCH is upregulated in inflamed intestinal mucosa in humans with colitis and MCH-deficient mice treated with trinitrobenzene-sulfonic acid (TNBS) develop an attenuated form of colitis compared to wild type animals. Zebrafish have emerged as a new animal model of IBD, although the majority of the reported studies concern zebrafish larvae. Regulation MCH expression in the adult zebrafish intestine remains unknown. METHODS: In the present study we induced enterocolitis in adult zebrafish by intrarectal administration of TNBS. Follow-up included survival analysis, histological assessment of changes in intestinal architecture, and assessment of intestinal infiltration by myeloperoxidase positive cells and cytokine transcript levels. RESULTS: Treatment with TNBS dose-dependently reduced fish survival. This response required the presence of an intact microbiome, since fish pre-treated with vancomycin developed less severe enterocolitis. At 6 hours post-challenge, we detected a significant influx of myeloperoxidase positive cells in the intestine and upregulation of both proinflammatory and anti-inflammatory cytokines. Most importantly, and in analogy to human IBD and TNBS-induced mouse experimental colitis, we found increased intestinal expression of MCH and its receptor in TNBS-treated zebrafish. CONCLUSIONS: Taken together these findings not only establish a model of chemically-induced experimental enterocolitis in adult zebrafish, but point to effects of MCH in intestinal inflammation that are conserved across species.

An attenuated Salmonella enterica serovar Typhimurium strain lacking the ZnuABC transporter induces protection in a mouse intestinal model of Salmonella infection.

Salmonella enterica serovar Typhimurium has long been recognised as a zoonotic pathogen of economic significance in animals and humans. Attempts to protect humans and livestock may be based on immunization with vaccines aimed to induce a protective response. We recently demonstrated that the oral administration of a Salmonella enterica serovar Typhimurium strain unable to synthesize the zinc transporter ZnuABC is able to protect mice against systemic salmonellosis induced by a virulent homologous challenge. This finding suggested that this mutant strain could represent an interesting candidate vaccine for mucosal delivery. In this study, the protective effect of this Salmonella strain was tested in a streptomycin-pretreated mouse model of salmonellosis that is distinguished by the capability of evoking typhlitis and colitis. The here reported results demonstrate that mice immunized with Salmonella enterica serovar Typhimurium (S. Typhimurium) SA186 survive to the intestinal challenge and, compared to control mice, show a reduced number of virulent bacteria in the gut, with milder signs of inflammation. This study demonstrates that the oral administration a of S. Typhimurium strain lacking ZnuABC is able to elicit an effective immune response which protects mice against intestinal S. Typhimurium infection. These results, collectively, suggest that the streptomycin-pretreated mouse model of S. typhimurium infection can represent a valuable tool to screen S. typhimurium attenuated mutant strains and potentially help to assess their protective efficacy as potential live vaccines.

Clinical experience in 89 consecutive cases of chronic radiation enterocolitis.

BACKGROUND: Pelvic irradiation has been a popular therapy modality for cervical cancer for many years, and its usage in rectal cancer and prostate cancer cases is on the rise. However, it is associated with significant side effects. In this study, we compared the different characteristics of surgical and nonsurgical patients who were treated for radiation enterocolitis, the treatment results, posttreatment quality of life (QOL), nutrition status, and predisposing factors for surgery. METHODS: From 1985 to 2009, the records of a total of 89 patients with chronic radiation enterocolitis in our hospital were retrospectively reviewed for demographic data, operative data and long-term treatment results. Posttreatment QOL and nutrition status were also recorded. Univariate and multivariate analyses were performed to identify the independent predicting factors associated with surgical intervention. Characteristics of surgical and nonsurgical patients were compared. RESULTS: Radiotherapy before 1995, concomitant radiation uropathy and smoking were independent predictive factors for surgery. Surgical and nonsurgical cases had similar Kaplan-Meier curves. Although the recurrence rate of radiation enterocolitis was much higher for the surgical group (p = 0.031), both groups had similar QOL score (median: 8 vs.7; p = 0.709), serum albumin level (3.29 g/dL vs. 3.16 g/dL; p = 0.095), and body mass index (20.19 vs. 19.86; p = 0.603). CONCLUSIONS: We confirmed that as compared with recently developed innovative techniques, early primitive radiotherapy techniques were associated with more severe radiotherapy complications that required surgery. Smoking may enhance patients' vulnerability to severe radiation injury. Surgery for radiation-induced intestinal obstruction, intestinal fistula and perforation is warranted because QOL, serum albumin level and body mass index were similar between the surgical and nonsurgical groups.

MyD88-dependent pathways mediate resistance to Cryptosporidium parvum infection in mice.

Cryptosporidium spp. cause diarrheal disease worldwide. Innate immune responses mediating resistance to this parasite are not completely understood. To determine whether MyD88-dependent pathways play a role in resistance to Cryptosporidium parvum, we compared the course of infection in MyD88(-/-) mice to that in their wild-type (WT) littermate controls. Three- to 4-week-old mice were infected with C. parvum, and infection was monitored by quantifying fecal oocyst shedding. Twelve days postinfection, the histology of the intestines was examined to quantify intestinal parasite burden and to determine if there were any pathological changes. Fecal oocyst shedding and intestinal parasite burden were significantly greater in MyD88(-/-) mice than in littermate controls. Nonetheless, both WT and MyD88(-/-) mice cleared the infection within 3 weeks. These results indicate that MyD88-dependent pathways are involved in mediating initial resistance to C. parvum. Since gamma interferon (IFN-gamma) is known to mediate resistance to C. parvum, we also studied infection in MyD88(-/-) mice and WT controls in which this cytokine was temporarily neutralized. Fecal oocyst shedding, as well as intestinal parasite burden, intestinal inflammation, and mortality, was significantly greater in MyD88(-/-) mice in which IFN-gamma was neutralized than in IFN-gamma-neutralized WT mice or in MyD88(-/-) mice in which this cytokine was active. These results suggest that MyD88 and IFN-gamma had an additive effect in conferring protection from C. parvum infection. While this study confirms the importance of IFN-gamma in conferring resistance to infection with C. parvum, it suggests that MyD88-mediated pathways also play a role in innate immunity to this parasite.