Adherence to the Mediterranean diet is associated with decreased fecal calprotectin in patients with ulcerative colitis after pouch surgery.

BACKGROUND: Mediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery. METHODS: Consecutive patients after pouch surgery due to ulcerative colitis (UC) were recruited at a comprehensive pouch clinic. Adherence to MED was calculated according to MED score, ranging from 0 (low adherence) to 9 (high adherence), based on food-frequency questionnaires. Pouch behavior was defined as normal pouch (NP) or pouchitis based on Pouchitis Disease Activity Index (PDAI) and disease activity was defined as active or inactive. C-reactive protein (CRP) and fecal calprotectin were assessed. RESULTS: Overall 153 patients were enrolled (male gender 47%; mean age 46 ± 14 years; mean pouch age 9.5 ± 7 years). MED scores were higher in patients with normal vs. elevated CRP and calprotectin levels (4.6 ± 1.8 vs. 4.4 ± 1.6, p = 0.28; 4.8 ± 1.8 vs. 4.07 ± 1.7, p < 0.05, respectively). In a multivariate regression, MED score was associated with decreased calprotectin levels (OR = 0.74 [0.56-0.99]). Adherence to MED was associated with dietary fiber and antioxidants intake. Finally, in a subgroup of patients with NP followed up for 8 years, higher adherence to MED trended to be inversely associated with the onset of pouchitis (log rank = 0.17). CONCLUSIONS: In patients with UC after pouch surgery, adherence to MED is associated with decreased calprotectin levels. Thus, MED may have a role in modifying intestinal inflammation in IBD.

Clinical recurrence and re-resection rates after extensive vs. segmental colectomy in Crohn's colitis: a retrospective cohort study.

BACKGROUND: The aim of the present study was to document long-term clinical recurrence and re-resection rates of segmental and extended colectomy in patients with Crohn's colitis and to identify risk factors causing recurrence. METHODS: Records of patients with isolated colonic Crohn's disease who underwent colectomy between 1995 and 2013 and were followed at our medical center were identified. Data on age at diagnosis, gender, smoking, disease location at diagnosis, perianal and rectal disease, indication for surgery, preoperative disease duration, type of operation, primary anastomosis at first operation, length of resected specimen, recurrence of symptoms, postoperative medication, reoperation, and total follow-up time were retrieved. RESULTS: Thirty-five suitable patients (18 segmental colectomy, 17 extensive colectomy; 17 males; mean age at operation 36.6 years) were identified. Mean age at primary operation was 36 years. The mean preoperative disease duration was 121 months. Postoperative medical treatment was needed in 10 (56 %) patients undergoing segmental colectomy and in 16 (94 %) of those undergoing extensive colectomy (p = 0.01). There was longer reoperation-free survival in the segmental colectomy patient group (p = 0.02) and also a trend toward longer symptom-free survival compared to the extensive colectomy patient group (p = 0.105). There was no correlation between the length of resected bowel and recurrence. Patients operated on at a younger age did not have a higher rate of recurrence of symptoms. Shorter disease duration, smoking, and male gender were risk factors for clinical recurrence. CONCLUSIONS: Segmental resection with primary anastomosis can be safely performed in patients with limited Crohn's colitis with reasonable clinical recurrence rates.

Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study.

Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

Simultaneous immunostaining with anti-S100P and anti-SV40 antibodies revealed the origin of BK virus-infected decoy cells in voided urine samples.

BACKGROUND: Methods for determining the origin of BK virus (BKV)-infected cells (decoy cells) in clinical urine samples have not been established although they could enhance the diagnosis of BKV infection in immunocompromised patients. METHODS: We performed simultaneous immunostaining with anti-S100P (a urothelial marker) and anti-SV40 antibodies in 66 clinical urine samples exhibiting SV40 positivity and a decoy-cell appearance on Papanicolaou staining. The clinical voided urine samples included seven cases of renal transplantation, 47 cases of cancer therapy and 12 cases of non-neoplastic disease. SurePath(™) liquid-based cytology was used for the urine samples. RESULTS: BKV-infected cells were categorized as SV40(+)/S100P(+) and SV40 (+)/S100p(-). SV40(+)/S100P(-) cells were found in 55 cases (83.4%); nine cases (13.6%) carried both SV40(+)/S100P(-) and SV40(+)/S100P(+) cells. The former were identified as BKV infection in renal tubules and the latter in both the renal tubules and urothelial epithelia. The remaining two cases (3.0%) had only SV40(+)/S100P(+) cells of urothelial origin. CONCLUSION: Simultaneous immunostaining with anti-S100P and anti-SV40 is a useful method for determining the origin of BKV-infected cells in clinical urine samples from immunocompromised patients such as renal transplantation recipients.

Nucleic acid sensing and beyond: virtues and vices of high-mobility group box 1.

High-mobility group box 1 (HMGB1) was first described as an architectural chromatin-binding protein. Today, a wealth of evidence indicates that this protein is very versatile and serves an amazing assortment of roles in the nucleus, cytoplasm and extracellular milieu. As a result, HMGB1 is fast becoming recognized as a key regulator of protective and pathological immune responses. Whilst acknowledging the many functions of HMGB1 and its family members, we focus this review on their role as broad effectors of immune responses mediated by nucleic acids. In addition, we touch upon the recent progress in determining the in vivo role of HMGB1 as revealed by the study of mice conditionally null for the Hmgb1 gene.

Association of TLR polymorphisms with development of tuberculosis in Indonesian females.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is a major cause of morbidity and mortality worldwide. Many candidate genes have been investigated for a possible association with TB. Toll-like receptors (TLRs) are known to play important roles in human innate immune systems. Polymorphisms in and functions of TLRs have been investigated to identify associations with specific infectious diseases, including TB. Here, we examined whether single-nucleotide polymorphisms (SNPs) in TLRs and genes in TLR signaling were associated with TB susceptibility in Indonesian and Vietnamese populations. A statistically significant association was observed between TB susceptibility in a classified Indonesian female group and rs352139, an SNP located in the intron of TLR9, using the genotype (P = 2.76E-04) and recessive (AA vs AG+GG, P = 2.48E-04, odds ratio = 1.827, 95% confidence interval = 1.321-2.526) models. Meta-analysis of the Indonesian and Vietnamese populations showed that rs352139 was significantly associated with TB in the recessive model. This finding indicated that a TLR9 polymorphism might have an important role in the susceptibility to M. tuberculosis in Asian populations.

Increasing adherence to the Mediterranean diet and lifestyle is associated with reduced fecal calprotectin and intra-individual changes in microbial composition of healthy subjects.

The Mediterranean diet (MED) is associated with the modification of gut microbial composition. In this pilot study, we investigate the feasibility of a microbiota-targeted MED-based lifestyle intervention in healthy subjects. MED intervention integrating dietary counseling, a supporting mobile application, and daily physical activity measurement using step trackers was prospectively applied for 4 weeks. Blood and fecal samples were collected at baseline, after the 4-week intervention, and at 6 and 12 months. Blood counts, inflammatory markers, microbial and eukaryotic composition were analyzed. Dietary adherence was assessed using daily questionnaires. All 20 healthy participants (females 65%, median age 37), completed the 4-week intervention. Adherence to MED increased from 15.6 ± 4.1 (baseline) to 23.2 ± 3.6 points (4 weeks), p < .01, reflected by increased dietary fiber and decreased saturated fat intake (both p < .05). MED intervention modestly reduced fecal calprotectin, white blood cell, neutrophil, and lymphocyte counts, within the normal ranges (P < .05). Levels of butyrate producers including Faecalibacterium and Lachnospira were positively correlated with adherence to MED and the number of daily steps. Bacterial composition was associated with plant-based food intake, while fungal composition with animal-based food as well as olive oil and sweets. Increasing adherence to MED correlated with increased absolute abundances of multiple beneficial gut symbionts. Therefore, increasing adherence to MED is associated with reduction of fecal calprotectin and beneficial microbial alterations in healthy subjects. Microbiota targeted lifestyle interventions may be used to modify the intestinal ecosystem with potential implications for microbiome-mediated diseases.

Essential role of high-mobility group box proteins in nucleic acid-mediated innate immune responses.

Central to protective and pathological immunity is the activation of innate immune responses upon recognition of nucleic acids by transmembrane Toll-like receptors (TLRs) and cytosolic receptors. In mammals, the transmembrane pattern recognition receptors TLR3, TLR7 and TLR9 recognize double-stranded RNA, single-stranded RNA and hypomethylated DNA, respectively, while the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), RIG-I and MDA5 are known to be cytosolic RNA-sensing receptors. In addition, cytosolic DNA-sensing receptors that include DAI, RIG-I/MDA5 and AIM2 also trigger innate immune responses. High-mobility group box (HMGB)1, 2 and 3 proteins, which also bind immunogenic nucleic acids, are generally involved in the nucleic acid receptor-mediated activation of innate immune responses. There is a hierarchy in the nucleic acid-mediated activation of immune responses, wherein the selective activation of the nucleic acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. The aim of this review is to summarize this novel feature of HMGB proteins, as essential frontline instigators of nucleic acid-mediated activation of innate immune responses. In addition, we will discuss the therapeutic implications of these findings.

Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis.

Chromosome 5q31 spans the T helper (Th) 2-related cytokine gene cluster, which is potentially important in Th1/Th2 immune responses. The chromosome 5q23.2-31.3 has been recently identified as a region with suggestive evidence of linkage to tuberculosis in the Asian population. With the aim of fine-mapping a putative tuberculosis susceptibility locus, we investigated a family-based association test between the dense single nucleotide polymorphism (SNP) markers within chromosome 5q31 and tuberculosis in 205 Thai trio families. Of these, 75 SNPs located within candidate genes covering SLC22A4, SLC22A5, IRF1, IL5, RAD50, IL13, IL4, KIF3A and SEPT8 were genotyped using the DigiTag2 assay. Association analysis revealed the most significant association with tuberculosis in haplotypes comprising SNPs rs274559, rs274554 and rs274553 of SLC22A5 gene (P(Global)=2.02 x 10(-6)), which remained significant after multiple testing correction. In addition, two haplotypes within the SLC22A4 and KIF3A region were associated with tuberculosis. Haplotypes of SLC22A5 were significantly associated with the expression levels of RAD50 and IL13. The results show that the variants carried by the haplotypes of SLC22A4, SLC22A5 and KIF3A region potentially contribute to tuberculosis susceptibility among the Thai population.

Genome-wide SNP-based linkage analysis of tuberculosis in Thais.

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.

Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam.

BACKGROUND: The association between environmental tobacco smoking (ETS) and childhood pneumonia has not been established in developed or developing countries. A study was conducted to assess the effect and impact of ETS exposure on pneumonia among children in central Vietnam. METHODS: A population-based large-scale cross-sectional survey was conducted covering all residents of 33 communes in Khanh Hoa Province, the central part of Vietnam. Information on demographics, socioeconomic status and house environment, including smoking status of each household member, was collected from householders. Hospital admissions for pneumonia among children aged <5 years in each household in the previous 12 months were recorded based on caregiver's report. RESULTS: A total of 353 525 individuals living in 75 828 households were identified in the study areas. Of these, 24 781 (7.0%) were aged <5 years. The prevalence of ETS was 70.5% and the period prevalence of hospital admissions for pneumonia was 2.6%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. CONCLUSIONS: Children in Vietnam are exposed to substantial levels of ETS which results in 44 000 excess hospital admissions due to pneumonia each year among children aged <5 years.

Choledochal cyst associated with duodenal atresia: case report and review of the literature.

We report a rare case of choledochal cyst (CC) associated with congenital duodenal atresia (DA) and annular pancreas (AP). A girl was born at 37 weeks of gestation weighing 2,974 g with a prenatal diagnosis of DA. She underwent a duodenoduodenostomy for type III DA with an AP 1 day after birth. At 4 years of age, she was admitted for evaluation of cholangitis and pancreatitis. Radiological studies demonstrated a fusiform-type CC with pancreaticobiliary maljunction (PBMJ). Excision of the CC and hepaticojejunostomy were performed. The patient was discharged without complications. Despite the fact that CC, DA, and AP are embryologically closely related entities, to the best of our knowledge, only eight such cases have been documented. We must be aware of the possible combination of CC in the follow-up of the patients with DA associated with AP.

Indo-Oceanic Mycobacterium tuberculosis strains from Thailand associated with higher mortality.

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province.OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality.DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models.RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death.CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.

National HIV prevalence surveillance among TB patients through periodic surveys: experience in Cambodia.

SETTING: The National Tuberculosis Programme (NTP) in Cambodia, one of the countries most affected by tuberculosis (TB) and human immunodeficiency virus (HIV) infection in Asia. OBJECTIVE: To conduct national HIV prevalence surveillance among TB patients, to estimate HIV prevalence among TB patients and to determine the potential of the NTP as a source for antiretroviral treatment (ART) scale-up. DESIGN: Anonymous unlinked cross-sectional seroprevalence surveys including all TB patients registered by the NTP in January 2003 and January 2005. RESULTS: HIV prevalence among all TB patients fell from 11.8% in 2003 to 9.9% in 2005 (P < 0.05). In 2003 and 2005, respectively 265 and 261 TB patients were identified as HIV-positive in a given month. Among new smear-positive pulmonary TB patients, the prevalence dropped from 8.2% to 5.2% (P < 0.01). CONCLUSION: The two periodic surveys demonstrated a high prevalence of HIV among TB patients in Cambodia. However, the declining incidence of HIV from the late 1990s might now be reflected in the HIV prevalence among new smear-positive TB patients. The NTP is a potential source of ART if HIV counselling and testing are made more widely available to TB patients.

Patient satisfaction with endoscopy measurement and assessment.

BACKGROUND: Several factors could influence patient satisfaction with endoscopy including technical quality of care, comfort and tolerability of the procedure, whether informed consent has been obtained, the level of communication with staff before and after the procedure, and delays in appointments. AIM: To assess what factors should be measured in assessing patient satisfaction by using a 16-point questionnaire based on the informed consent recommendations of the first workshop at Kos, and of the criteria of the American Society for Gastrointestinal Endoscopy (ASGE), and to compare the response of patients with gastroenterologists and the support staff. METHOD: The questionnaire was answered by 81 patients, 71 gastroenterologists and 36 support staff (nurses and receptionists). It graded the relative importance of different factors which influenced the perception of satisfaction in those undergoing endoscopy. These factors included: the waiting time for appointment, the explanation received at various stages before and after the procedure, the reception process, the importance of premedication against pain and discomfort, privacy and satisfaction related to findings at the procedure. RESULTS: Thirteen of the 16 factors were generally graded as important for patient satisfaction. The finding at endoscopy, a written explanation and the alternatives to the endoscopic procedure were regarded as of lesser importance. Gastroenterologists tended to rate the importance of a written explanation and the explanations from the nurses before and after the procedure lower than did the patients and nursing staff. CONCLUSIONS: The courtesy and personal manner of the entire medical staff, as evidenced by the explanation of the procedure by the various physicians before and after and the process of admission, were generally rated of the highest importance. The nurses' ranking of the various factors was closer to that of the patients than of the gastroenterologists.

Dysmenorrhea among Japanese women.

OBJECTIVE: To investigate the epidemiology of dysmenorrhea in Japanese women of menstrual age. METHODS: A prospective cohort study was conducted using a health diary in a sample representative of Japanese women. Information on health care use was also collected. RESULTS: Among 823 enrolled participants (age range, 18-51 years), dysmenorrhea (mean duration 1.75 days; range 1-5 days) was reported in 15.8% (95% CI, 13.3-18.3) during the 1-month study period. Common associated symptoms included headache (10.77%), back pain (6.92%), and fatigue (5.38%). No participant with dysmenorrhea visited a physician, while 51.5% of the women used self-medication, and 7.7% used complementary/alternative medicine. CONCLUSION: Dysmenorrhea is common in Japanese women. In our study, about half used self-medication, while some preferred complementary/alternative medicine. Dysmenorrhea is significantly associated with younger age and employment status.

Severe hypoglycemia in a patient with anorexia nervosa.

OBJECTIVE: Severe hypoglycemia is an important but uncommon complication of anorexia nervosa. A 35-year-old woman showed severe hypoglycemia after a recovery from severe liver dysfunction due to malnutrition. METHODS: To reveal the cause of severe hypoglycemia, we measured plasma hormones and performed a 75g oral glucose loading test. RESULTS: Fasting serum adrenocorticotropic hormone, cortisol, growth hormone, somatostatin, and active ghrelin were elevated. Serum free triiodothyronine, leptin, and adiponectin were reduced. Plasma glucose fluctuated from 67 to 76 mg/dl after a 75g glucose ingestion, without hyperinsulinemia. Serum growth hormone, somatostatin, and active ghrelin levels were decreased after glucose ingestion. Plasma glucagon levels were increased and remained at high levels at 120 min, and glucose-dependent insulinotropic polypeptide (GIP) levels were continuously and remarkably increased after glucose ingestion. CONCLUSION: We observed a strongly reduced sensitivity in glucagon-induced hepatic glycogenolysis, and significantly elevated fasting and postprandial GIP levels, and a defective GIP-mediated glucagon secretion, in an anorectic patient with severe hypoglycemia.

The feasibility and risk of early colonoscopy in acute diverticulitis: a prospective controlled study.

BACKGROUND AND STUDY AIM: Following acute diverticulitis, colonoscopy is advised to rule out malignancy. Commonly, the colonoscopy is postponed to avoid the potential risk of perforation. In a previous pilot, noncontrolled study, we showed that early colonoscopy is feasible in patients with acute diverticulitis. This randomized controlled trial compared early and late colonoscopy in hospitalized patients with acute diverticulitis. PATIENTS AND METHODS: 154 patients diagnosed with acute diverticulitis were hospitalized between January 2004 and June 2006. Of these, 35 patients were excluded because of either free perforation or pericolic air on computed tomography (CT), and another 18 because they had undergone colonoscopy in the previous year. The remaining 101 patients were offered the possibility of participating in the study, with random allocation to either early in-hospital colonoscopy or late colonoscopy, 6 weeks later. Randomization was refused by 15 patients, and 86 were included in the study. RESULTS: 45 patients were randomly allocated for early colonoscopy and 41 for late colonoscopy. Three and 10 did not present for the examination, in the early and late group respectively. The cecum could not be reached in eight and three patients from the early and late groups, respectively. The colonoscopy revealed polyps in five patients, two in the early group and three in the late group. No malignancy was detected. There were no complications in either group. CONCLUSIONS: Early colonoscopy in acute diverticulitis is feasible and safe in the absence of pericolic air on CT, and has greater compliance. However, no added value is apparent compared with the CT scan currently used.

A survey of tuberculosis prevalence in Hanoi, Vietnam.

OBJECTIVE: To assess the prevalence of tuberculosis (TB) in Hanoi, Vietnam, in 2003/2004. METHODS: A random selection was carried out involving 11624 subjects from 20 communes within the city. RESULTS: On chest X-ray examination, 317 subjects (2.73%) showed abnormal lung opacity, of which 17 were sputum smear-positive, two concentrated smear-positive and three culture-positive, all with active TB. The prevalence of sputum smear-positive pulmonary TB was 146 per 100000 in persons aged >or=15 years (95%CI 65-228). CONCLUSION: This is the first large-scale assessment of the prevalence of TB in Hanoi. The prevalence rate was higher than expected, suggesting that a significant number of patients with active TB, particularly females, remain undiagnosed, thus representing a continuing potential source of transmission in the community.