Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran.

This study investigated the molecular epidemiology of carbapenem-resistant classic Klebsiella pneumoniae (CR-cKp) and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolates in southwestern Iran. From 2019 to 2021, 136 (88.9%) cKp and 17 (11.1%) hvKp isolates were identified using biochemical tests and polymerase chain reaction (PCR). Antibiotic resistance, beta-lactamases, and clonal relatedness of carbapenem-resistant isolates were investigated using disk diffusion, PCR, and enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), respectively. The different markers of hvKp isolates were as follows: string test (35.3%, n = 6/17), magA (11.8%, n = 2/17), rmpA (11.8%, n = 2/17), rmpA2 (52.9%, n = 9/17), iucA (52.9%, n = 9/17), and peg344 (35.3%, n = 6/17). Also, 55.1% (n = 75/136) of cKp and 47.1% (n = 8/17) of hvKp isolates were CR-cKp and CR-hvKp, respectively. All CR-hvKp (100.0%, n = 8) isolates were MDR. Colistin, tetracycline, and tigecycline were the most effective antibiotics. The occurrence of beta-lactamase genes in 75 CR-cKp and 8 CR-hvKp isolates was as follows: bla NDM (41.3, 25.0%), bla IMP (4.0, 0.0%), bla VIM (8.0, 0.0%), bla GES (14.7, 25.0%), bla OXA-48-like (20.0, 0.0%), bla CTX-M (26.7, 12.5%), bla SHV (24.0, 12.5%), bla TEM (10.7, 0.0%), bla FOX (6.7, 0.0%), bla DHA (6.7, 0.0%), bla CMY (5.3, 0.0%), bla LAT (12.0, 0.0%), and bla ACT (8.0, 0.0%). ERIC-PCR showed a high diversity among isolates. In this study, the occurrence of MDR CR-hvKp isolates harboring bla NDM and bla GES was detected for the first time in southwestern Iran. To prevent the spread of CR-hvKp and reduce selection pressure, long-term surveillance and more effective treatment strategies should be implemented.

IS DAIRY FOODS RESTRICTION MANDATORY FOR INFLAMMATORY BOWEL DISEASE PATIENTS: A MULTINATIONAL CROSS-SECTIONAL STUDY.

BACKGROUND: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. OBJECTIVE: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. METHODS: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). RESULTS: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). CONCLUSION: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

A restrição de alimentos lácteos é obrigatória para pacientes com doença inflamatória intestinal? Estudo transversal multinacional / Is dairy foods restriction mandatory for inflammatory bowel disease patients: a multinational cross-sectional study

ABSTRACT Background: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. Objective: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. Methods: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). Results: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). Conclusion: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

RESUMO Contexto: O papel dos alimentos lácteos na doença inflamatória intestinal (DII) tem sido controverso e é discutível se os pacientes com DII devem ou não evitar leite e laticínios, bem como a relação entre esses alimentos e sintomas nesta população. Objetivo: Estudo transversal multicêntrico foi projetado para avaliar se é realmente necessário privar os pacientes com DII do consumo desta classe de alimentos. Métodos: Um estudo multicêntrico com 12 centros de referência em gastroenterologia de quatro países foi projetado para avaliar sintomas gastrointestinais após o consumo de alimentos lácteos em todos os ambulatórios de DII durante seis meses e comparar pacientes tratados nos mesmos centros sem DII. Resultados: No total, foram incluídos 1888 casos (872 pacientes com DII e 1016 casos sem DII. 56,6% dos participantes eram do sexo feminino com idade média de 40,1 anos. 79,8% dos participantes eram caucasianos e originalmente eram cidadãos de 10 países. A prevalência relativa de DII foi maior em africanos e indianos e a prevalência mais frequente de intolerância a alimentos lácteos observada nos asiáticos. Entre os pacientes com DII, 571 casos foram diagnosticados como colite ulcerativa e 189 participantes como doença de Crohn. A duração média do diagnóstico como DII foi de 6,8 anos (de 2 meses a 35 anos). Os sintomas de gastrointestinais mais prevalentes após o consumo de todos os alimentos lácteos foram inchaço e dor abdominal. No total, a intolerância aos alimentos lácteos e a deficiência de lactase foi mais prevalente entre os pacientes com DII em comparação com os casos sem DII (65,5% vs 46,1%, P=0,0001). A taxa de queixas gastrointestinais entre os pacientes com DII que não tinham histórico familiar de deficiência de lactase, histórico de sensibilidade alimentar ou ambos foram de 59,91%, 52,87% e 50,33% respectivamente e semelhantes aos casos sem DII (P=0,68, 0,98 e 0,99, respectivamente). Conclusão: A taxa de intolerância de alimentos lácteos entre pacientes com DII sem histórico familiar de deficiência de lactase ou histórico de sensibilidade alimentar é semelhante aos casos sem DII e provavelmente não há razão para privá-los dessa importante fonte de cálcio dietético, vitamina D e outros nutrientes.

Occult Hepatitis B Virus Infection among ß-Thalassemia Major Patients in Ahvaz City, Iran.

Occult Hepatitis B Infection (OBI) is a critical risk factor for triggering post-transfusion hepatitis (PTH), cirrhosis, hepatocellular carcinoma, and hepatitis B virus (HBV) reactivation, which ß-thalassemia major (BTM) patients are at risk of it due to multiple blood transfusions. This study was aimed at determining the prevalence of OBI among BTM patients from Khuzestan Province, Iran. In this cross-sectional study, 90 thalassemia patients, who have received blood 36 to 552 times, participated referred to the Shafa hospital of Ahvaz city from January 2018 to April 2019. ELISA for determining serological markers (HBsAg, anti-HBc, anti-HBs, and anti-HCV) and real-time PCR for detecting HBV-DNA were performed; Nested PCR was conducted for DNA sequencing and determining the genotype of OBI case. Phylogenetic and statistical analyses were done by R package. Of 90 subjects enrolled in this study; 95.5% (86/90) were HBsAg negative, and the frequency of OBI among them was 1.16% (1/86). The anti-HBs, anti-HBc, and anti-HCV were detected in 80.00%, 7.78%, and 12.2% of patients, respectively. HBV-DNA was assessed at four HBsAg-positive subjects as well, and all of them were negative. The phylogenetic analysis showed that the detected HBV DNA in the OBI case belongs to the genotype D. This research, for the first time, demonstrated that OBI is present among ß-thalassemia patients in Iran. Also, further studies are necessary to determine the actual prevalence of OBI among BTM patients in Iran to decisions concerning OBI screening, especially in transfusion centers.

Prevalence of occult hepatitis C virus infection in beta-thalassemia major patients in Ahvaz, Iran.

Occult hepatitis C virus infection (OCI) is defined by the presence of HCV RNA in peripheral blood mononuclear cells (PBMCs) and liver tissue cells despite the absence of HCV RNA in plasma. Currently, OCI is classified into two types: seropositive OCI (anti-HCV positive and serum HCV RNA negative) and seronegative OCI (anti-HCV and serum HCV RNA negative). Beta-thalassemia is described as a blood disorder that decreases the synthesis of hemoglobin. Repeated blood transfusion is the standard treatment for patients with beta-thalassemia major (BTM), and this increases the risk of exposure to infectious agents. The aim of this study was to investigate the prevalence of OCI among BTM patients. Plasma and PBMCs were collected from 90 BTM patients who were referred to Shafa Hospital in the city of Ahvaz and were screened for HCV antibody using a commercial ELISA kit as the first step. Next, nested RT-PCR was performed on extracts of plasma and PBMCs. HCV RNA from positive PBMCs was sequenced, the sequences were aligned, and a phylogenetic tree was constructed to determine their relationship to reference sequences retrieved from the GenBank database. Seventy-nine out of 90 patients (87.8%) were negative for HCV Ab (seronegative), while 11 patients (12.2%) were seropositive. HCV RNA was found in PBMCs of four patients (66.7%) who were negative for HCV Ab (seronegative) and two patients (33.3%) who were positive for HCV Ab (seropositive). HCV RNA was not detected in plasma samples from these six patients. Six out of 90 BTM patients (6.7%) had OCI. HCV genotyping revealed that all six patients were infected with HCV subtype 3a. We found a high frequency of OCI in BTM patients, which warrants more attention, considering the importance of this infection. Further studies are needed to determine the actual prevalence of OCI in BTM patients in Iran.

The Efficacy and Safety of Modified Docetaxel, Cisplatin, and 5-Fluorouracil Vs. Epirubicin, Oxaliplatin, and Capecitabine Regimen in the Advanced Gastric Cancer: A Randomized Controlled Clinical Trial.

INTRODUCTION: One of the major challenges of advanced gastric cancer treatment is the lack of a standard regimen for patients. However, several clinical trials have shown that modified docetaxel, cisplatin, and 5-fluorouracil (m-DCF) and epirubicin, oxaliplatin, and capecitabine (EOX) regimens are superior to other regimens. METHODS: This randomized, single-center clinical trial was performed on 40 patients with advanced gastric cancer. The first group received the m-DCF regimen as follows: docetaxel (40 mg/m2) on the first day; cisplatin (40 mg/m2) on the first and second days; and 5-fluorouracil (400 mg/m2) from the first to fourth day. The second group received the EOX regimen, including epirubicin (50 mg/m2) and oxaliplatin (130 mg/m2) i.v on the first day and capecitabine at a twice-daily dose of 625 mg/m2 p.o for 21 days. Treatment was applied every three weeks for a total of eight cycles in both groups. In each group, the overall and progression-free survival rates and toxicity were assessed. RESULTS: A total of 40 patients were enrolled in this study (21 samples in the m-DCF group and 19 samples in the EOX group), 62.5% of whom were male. The median survival rate was 14.00 (95% CI: 11.82-16.18) months in the m-DCF group and 15.00 (95% CI: 9.56-20.43) months in the EOX group; however, differences between the groups were not significant. The progression-free survival rate was higher in the EOX group, although there was no significant difference between the two groups. Also, there was no significant difference regarding the side effects (e.g., toxicity) or need for supportive care between the groups. CONCLUSION: It seems that both m-DCF and EOX regimens are similar in terms of survival and toxicity and are recommended as first-line treatment for advanced gastric cancer with respect to the patient's status.

A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD) are classified as chronic inflammatory bowel diseases (IBD) which have similar symptoms and lead to digestive disorders and inflammation in the digestive system. The reason why they occur is still a mystery. A number of factors can be attributed to the prevalence of CD and UC, some of which include geographical location, inappropriate diet, genetics, and inappropriate immune response. Both diseases are more often diagnosed in urban areas compared to rural areas and both have their own challenges and side effects, but the patients can still have a good quality of life. Given the fact that the prevalence of this disease is higher at younger ages and that it disrupts half the life of the patient, it will, most likely, become a major health problem in the near future, even in developing countries. By reviewing valid scientific resources and evaluating new methods of addressing this disease, the present study aims to provide researchers and patients with new insights into this field and facilitate access to new treatments.

Comparison between gluten-free regime and regime with gluten in symptoms of patients with irritable bowel syndrome (IBS).

BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder and accounts for most of the referrals of patients to gastroenterologists. Given the high prevalence of this syndrome and its significant effect on the reduced quality of life of patients, the present study aimed to investigate the effect of using gluten-containing or gluten-free diet on symptoms of patients with irritable bowel syndrome. MATERIALS AND METHODS: In this trial, 140 patients with irritable bowel syndrome who referred to Imam Khomeini Hospital (2006) were randomly divided into two groups based on Rome III criteria. Seventy patients received a gluten-free diet and rest patent received a regular diet as control group for 12 weeks. In order to compare the quantitative characteristics, independent samples T-test was used, while Mann-Whitney and Z-tests were used to compare the qualitative characteristics. FINDINGS: There was no significant difference between the control group (9.8 ± 37 years) and the group with gluten-free diet (0.2 ± 37 years) in terms of mean age. The effect of gluten-free diet on intestinal gas, fecal consistency, urgent need for expulsion, and insufficient defecation were higher than in control group. Although abdominal pain and reduced frequency of bowel movements were higher in the control group than gluten-free diet group (P < 0.05). The positive response to general improvement in the gluten-free group and in the control group was 67% and 52%, respectively. CONCLUSION: According to present results, providing gluten-free diet could be improved patient treatment's symptoms. Also, it seemed that the duration of treatment can lead to better therapeutic outcomes.

An investigation into the sensitivity of endoscopic ultrasound in the diagnosis of malignant bile duct in patients with idiopathic acute pancreatitis.

INTRODUCTION AND OBJECTIVE: Acute pancreatitis (AP) is an inflammatory process of the pancreas characterized by abdominal pain and increased pancreatic enzymes. This disease is diagnosed clinically. Endoscopic ultrasound (EUS), which is a technique with high sensitivity and specificity, is used to diagnose biliary disease. This study aimed to determine the sensitivity of EUS in the diagnosis of malignant bile duct in patients with idiopathic AP. METHODS: This descriptive study was performed on 146 patients with pancreatitis hospitalized in the gastrointestinal tract section of the Imam Khomeini Hospital of Ahwaz Jundishapur University of Medical Sciences. The collected data were analyzed by the SPSS 22.0 and the significance level of the test was <0.05. RESULTS: According to the results, 79 (54%) out of the 146 patients were female and 67 (46%) were male. The mean and standard deviation of the patients' age were 52.5 and 19.6 years, respectively. The findings showed that the sensitivity and specificity of the EUS were 33% and 99%, respectively. Compared to the endoscopic retrograde cholangiopancreatography (ERCP), the sensitivity and specificity of the abdominal ultrasound were 62% and 62.5%, respectively. Compared to the ERCP, the sensitivity and specificity of EUS were 92% and 50%, respectively. CONCLUSION: The findings of this study showed that the sensitivity and specificity of EUS were higher than those of abdominal ultrasound. Moreover, EUS was the preferred method to detect common bile duct stones (CBDS).

Study on JV Virus in Patients with Colon Cancer Type Adenocarcinoma

Colorectal cancer is the most repetitious malignancies with high mortality worldwide. JC virus (JCV) is ubiquitous Polyomavirus, with seroprevalence rates ranging from 70% to 90% in adult population. Recently the role of JCV have been reported in many malignant tumors worldwide. The association of JCV was reported in patients with colon and rectum cancers. Thus this study was conducted to evaluate the association of JCV DNA in patients with colon cancer type Adenocarcinoma. Material and Methods: A total of 120 formalin-fixed paraffin-embedded tissue blocks samples were collected including 20/40(50%) males, 20/40(50%) females patients with Colorectal Cancer(CRC), and 80 (50% males, 50% females) patients with benign tumor as a control. DNA was extracted for all the samples. Nested PCR was carried out for detection of Vp1/T-Ag junction genome in JCV genome by Nested-PCR assay. Randomly, PCR products of 6 samples were sequenced to analysis the partial JCV DNA. The phylogeny tree was constructed to determine homology identity with other JCV. Results: 4/40(10%) samples of test group and 10/80 (12.5%) of control samples were positive for JCV DNA (P= 0.69). Out of 4 samples positive for JC DNA, 3(7.5%) were males and 1(2.4%) female (P=0.29). The frequency of JCV DNA in age group> 50 years was 4/32(10%), while in age group <50 years was 0/8 (0%) (p= 0.29). Conclusion: prevalence of JCV DNA was among 10% patients with CRC and 12.5% benign tumors (p=0.69). The distribution of JCV DNA was among 7.5% male and 2.5% female (p= 0.29). The frequency of JCV DNA was among 10% cases of age group >50 years and 0% of age group <50 years (P= 0.29). The subsequent T-Ag protein expression might explain the increased risk of colorectal cancer and requires further investigation.

Genetic basis for metronidazole and clarithromycin resistance in Helicobacter pylori strains isolated from patients with gastroduodenal disorders.

BACKGROUND: The aim of this study was to evaluate the antimicrobial resistance and genetic basis for metronidazole (Mtz) and clarithromycin (Cla) resistance in strains of Helicobacter pylori, isolated from patients with gastroduodenal disorders. PATIENTS AND METHODS: A total of 157 H. pylori isolates (from 22 gastric cancer, 38 peptic ulcer disease, and 97 non-ulcer dyspepsia patients) were analyzed for drug susceptibility to Mtz and Cla, by gradient diffusion test (E-test, MAST). The PCR and sequence analysis of the rdxA and frxA for Mtz-resistant strains and the 23S rRNA for Cla-resistant strains were used to determine the genetic basis of drug resistance in H. pylori strains. Increased expression of TolC homologous genes (hefA) that upregulates efflux pump activity was determined in multidrug-resistant (MDR) strain of H. pylori by real-time PCR technique. RESULTS: Among 157 H. pylori isolates, 32 (20.4%) strains were resistant to at least one of the antimicrobial agents. The highest resistance rate was attributed to Mtz (n=69, 43.94%). Among the resistant strains of H. pylori, 15 cases (9.55%) were detected as MDR. Mutations in the rdxA (85.5%) and A2143G point mutations (63.1%) in the 23S rRNA were the most common cause of resistance to Mtz and Cla in strains of H. pylori, respectively. In MDR strains, the rdxA mutation and A2143G-point mutation in the 23S rRNA were the most abundant mutations responsible for drug resistance. The relative expression of hefA in MDR strains (mean 3.706) was higher than the susceptible strains (mean 1.07). CONCLUSION: Mutational inactivation and efflux pump overexpression are two mechanisms that increase the resistance to H. pylori antimicrobial agents and the rate of MDR strains. In Iran, the mutations of rdxA and frxA in Mtz-resistant strains and A2143G and A2142G of the 23S rRNA in Cla-resistant strains were significant. The screening for these mutations could help to prevent antibiotic resistance, and to determine the most effective anti-H. pylori drugs.

Effect of a high-protein diet with ß-cryptoxanthin supplementation on metabolic risk factors, oxidative and inflammatory biomarkers in non-alcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled clinical trial.

BACKGROUND: Excessive hepatic fat is associated with increased metabolic risk factors, production of inflammatory factors, and oxidative stress. High protein intake might trigger an increased hepatic lipid oxidation through an increase in hepatic energy expenditure. Furthermore, the majority of randomized controlled trials (RCT) in humans have failed to show whether carotenoids can be used to prevent and treat non-alcoholic fatty liver disease (NAFLD). However, it is notable and contradictory that NAFLD is rapidly escalating in Iran and other countries with lower intakes of fruit and vegetables (as sources of ß-cryptoxanthin [ß-CX] and carbohydrates) and higher intake of carbohydrates (as an agent of NAFLD); and the effects of ß-CX and a high protein diet (HPD) on NAFLD need to be investigated further. METHODS/DESIGN: This study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for 12 weeks to receive daily ß-CX 6 mg supplementation combined with a HPD on levels of metabolic factors, ß-CX, glycemic and lipid profiles, inflammatory factors, adipocytokines, and body composition. Ninety-two eligible patients, aged 18-60 years, of both genders, who are obese and overweight (body mass index [BMI] 25-40 kg/m2) will be randomly assigned to four groups as follow: HPD + placebo; normal protein diet + ß-CX (NPD + ß-CX); HPD + ß-CX; and NPD + placebo (control group). Two populations will be analyzed in this work. The intention-to-treat (ITT) population includes all patients who will be randomized, while the per-protocol (PP) population includes all individuals who complete the 12- week intervention (i.e. study completers). DISCUSSION: Our findings from this trial will contribute to the knowledge of the relationship between ß-CX supplementation and a HPD on NAFLD patients and determination of optimal macronutrient ratios without energy restriction. TRIAL REGISTRATION: Iran clinical trials registry, IRCT2017060210181N10 . Registered on 20 June 2017.