Pathogenic Intestinal Bacteria Enhance Prostate Cancer Development via Systemic Activation of Immune Cells in Mice

A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc[superscript Min/+] mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc[superscript Min/+] mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.RO1CA108854National Institute of Environmental Health Sciences (Massachusetts Institute of Technology. Center for Environmental Health Sciences Pilot Project Award P30-ES002109

Selenoprotein P in Patients with Nonalcoholic Fatty Liver Disease

Objective Main aim of this study was to evaluate circulating selenoprotein P (SEPP) levels in patients with simple steatosis (SS) and nonalcoholic steatohepatitis (NASH) compared with healthy controls. Methods Thirty-one patients with biopsy-proven NAFLD (15 with SS, 10 with borderline NASH, 6 with definite NASH) and 27 matched controls without NAFLD were enrolled. Serum SEPP levels and liver function tests plus biochemical parameters were measured with ELISA and standard methods, respectively. Homeostatic model of assessment - insulin resistance (HOMA-IR) was calculated. Results SEPP levels were statistically different between groups (p-value for trend=0.043). In pairwise comparisons, SEPP was lower in definite NASH compared with controls (p=0.029), but not SS (p=0.18) or borderline NASH (p=0.35). SEPP was not different between controls, SS and borderline NASH. The unadjusted trend between the controls, SS and NASH patients remained essentially unchanged after adjustment for age, sex, log(ALT) and waist circumference, but it marginally lost significance when log(HOMA-IR) entered into the model. SEPP levels were not different between groups of different severity of steatosis, fibrosis, hepatocellular ballooning, lobular and portal inflammation. Conclusions Lower SEPP levels were observed in patients with definite NASH compared with controls, a finding warranting larger studies. © 2019 BMJ Publishing Group. All rights reserved

Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines.

There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA. Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model. Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8×10 <sup>8</sup> erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal. Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment

Violence as the Most Frequent Cause of Oral and Maxillofacial Injuries among the Patients from Low- and Middle-Income Countries-A Retrospective Study at a Level I Trauma University Emergency Department in Switzerland.

Preventive strategies can be developed by gathering more information about oral and maxillofacial injuries and oral pathologies in immigrants from low- to middle-income countries (LMIC). Additional information on the quality of care can also improve the allocation of clinical resources for the management of these patients. We studied immigrants from LMIC who presented in the emergency department (ED) at Berne University Hospital with dental problems or oral or maxillofacial injuries. The patient data included age, gender, nationality, the etiology and type of trauma and infection in the oral-maxillofacial area, and overall costs. The greatest incidence of maxillofacial injuries was observed in the age group of 16-35 years (n = 128, 63.6%, p = 0.009), with males outnumbering females in all age groups. Trauma cases were most frequent in the late evening and were mostly associated with violence (n = 82, 55.4%, p = 0.001). The most common fracture was fracture of the nose (n = 31). The mean costs were approximately the same for men (mean = 2466.02 Swiss francs) and women (mean = 2117.95 Swiss francs) with maxillofacial injuries but were greater than for isolated dental problems. In conclusion, the etiology of dental and maxillofacial injuries in immigrants in Switzerland requires better support in the prevention of violence and continued promotion of oral health education

Helicobacter pylori Infection and Gastroesophageal Reflux Disease–Barrett’s Esophagus–Esophageal Adenocarcinoma Sequence

[No abstract available

Impact of occupational stress on irritable bowel syndrome pathophysiology and potential management in active duty noncombat Greek military personnel: A multicenter prospective survey

IntroductionIrritable bowel syndrome (IBS) is one of the gut-brain axis interaction disorders. It has global distribution with varying prevalence and particular financial and psychological consequences. IBS has been associated with stress and anxiety, conditions that are usually prevalent in the army. There are scarce data investigating the impact of IBS on noncombat active duty military without reports of Greek military or stress in the occupational environment.Materials and methodsThe main exclusion criteria in our noncombat military multicenter prospective survey were gastrointestinal pathologies, malignancies, hematochezia, recent infections and antibiotics prescription, and pregnancy. Questionnaires included a synthesis of baseline information, lifestyle, and diet, psychological and stress-investigating scales and the IBS diagnosis checklist. Hospital Anxiety and Depression Scale and Rome IV criteria were utilized.ResultsAmong 1605 participants included finally, the prevalence of IBS was 8% and 131 cases were identified. Women were more vulnerable to IBS, although male sex was prevalent at a ratio of 3.5: 1 (male:female) in the entire sample. The mean age of all participants was 23.85 years; most of the IBS patients were older than thirty. Abnormal anxiety scores and high levels of occupational stress were related to an IBS diagnosis.DiscussionThis prospective multicenter survey showed, for the first time, the potential impact of occupational stress on IBS in active duty noncombat Greek Military personnel. The diagnosis of IBS by questionnaire is a quick, affordable way that can upgrade, by its management, the quality of life and relieve from the military burden. Our results are comparable with previous studies, although large-scale epidemiological studies are required for the confirmation of a possible causative relationship. © 2019 Lippincott Williams and Wilkins. All rights reserved

Letter: Helicobacter pylori in proton pump inhibitor-associated biliary disease

[No abstract available

Noggin levels in nonalcoholic fatty liver disease: the effect of vitamin E treatment

Aim: The evaluation of (a) noggin levels in patients with simple steatosis (SS) vs. nonalcoholic steatohepatitis (NASH) vs. controls, and (b) the effect of combined spironolactone plus vitamin E vs. vitamin E monotherapy on noggin levels in biopsy-proven patients with nonalcoholic fatty liver disease (NAFLD). Methods: In the case-control study, 15 patients with SS, 16 with NASH, and 24 controls were included. In the randomized controlled trial, NAFLD patients were assigned to vitamin E (400 IU/d) or spironolactone (25 mg/d) plus vitamin E for 52 weeks. Results: Noggin levels were lower in SS (5.8 ± 1.5 pmol/l) and NASH (8.7 ± 2.4 pmol/l) patients than in controls (13.7 ± 2.7 pmol/l; p for trend = 0.040), but were similar in SS and NASH patients. After adjustment for potential cofounders, log(noggin) remained different between groups. Log(noggin) levels similarly increased post-treatment in both groups: log(noggin) was not different between groups (p = 0.20), but increased within groups over time (p < 0.001), without a significant group × time interaction (p = 0.62). Log(noggin) significantly increased at month 2 post-treatment (p = 0.008 vs. baseline) and remained stable thereafter. Conclusions: Lower noggin levels were observed in NAFLD patients than in controls. Noggin levels increased similarly by either combined low-dose spironolactone plus vitamin E or vitamin E monotherapy. Trial registration: NCT01147523. © 2018, Hellenic Endocrine Society