High prevalence of MUTYH associated polyposis among minority populations in Israel, due to rare founder pathogenic variants.

BACKGROUND: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum. METHODS: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel. RESULTS: The Northern cohort included 37 patients from 30 unrelated families; 8(26.6%) carried bi-allelic MUTYH PVs. The major variant p.Glu452del was detected in 6/8 Druze and Muslim families who shared the same haplotype. Other PVs detected in both cohorts included p.Tyr56Ter, p.His57Arg, c.849+3A>C, p.Ala357fs, and p.Tyr151Cys. Among bi-allelic carriers, 88% reported consanguinity, and 100% had positive family history for polyposis or colorectal cancer (CRC). Generally, the age of CRC was 10 years younger than reported in the general MAP population. CONCLUSIONS: MAP accounted for 27% of polyposis cases in the Arab population of Northern Israel. PVs spectrum is unique, with high frequency of the founder variant p.Glu452del. Our results may inform the genetic testing strategy in the Israeli Arab population.

Characteristics of Antibiotic Resistance of Helicobacter pylori Among Adult Arab and Jewish Populations in Northern Israel.

AIMS: Following reports from various doctors regarding increased treatment failure in Helicobacter pylori infection among the Arab population, we decided to make a prospective comparison between the resistance rates of H. pylori in the Arab and Jewish populations in northern Israel. RESULTS: Among the Arab population, higher resistance rates were found for clarithromycin and levofloxacin (LEV), as well as a higher rate of multidrug resistance. Rifampin and LEV were found to have higher resistance rates in the village, whereas LEV had a higher resistance rate among women. CONCLUSIONS: Helicobacter pylori in the Arab population compared with the Jewish population in northern Israel is more resistant to treatment. We assume that these results are caused by overexposure combined with unwise use of antibiotics. A correlation was also found between the type of residence and resistance rates to various antibiotics. Further research is needed to determine the resistance mechanism that may explain these results. Due to the high resistance rate and treatment failure, it is appropriate to consider replacing the standard treatment of H. pylori in these populations.

GenoType® HelicoDR test in comparison with histology and culture for Helicobacter pylori detection and identification of resistance mutations to clarithromycin and fluoroquinolones.

BACKGROUND: There are several methods for Helicobacter pylori infection diagnosis. AIM: The efficacies of three methods for H. pylori identification directly from a biopsy were compared: histology, culture, and molecular GenoType® HelicoDR test. MATERIALS & METHODS: Eighty-five triplicates of stomach antrum biopsies were obtained during gastroscopy procedures for culture, histology, and molecular assay. In addition, we performed molecular identification of genes encoding resistance to clarithromycin and fluoroquinolones. RESULTS: The results have shown that the most specific method with the highest number of positive specimens was by molecular kit, compared to culture and histology (94.3%, 77.1%, and 71.4%, respectively). There was a higher rate of resistance mutations to clarithromycin than to fluoroquinolones (68.26% vs 20%). The most common mutations for clarithromycin and fluoroquinolones resistance were found in alleles A2143G and N87K, respectively. The highest rate of positive specimens was identified by the molecular. DISCUSSION: GenoType HelicoDR kit (94.3%), which has several advantages: direct identification, strain resistance characterization, mixture of genotypes detection, and no transport or storage limitations; thus, it is an excellent epidemiological screening tool. This work has demonstrated a lower resistance rate to fluoroquinolones; it is possible that in the investigated geographic area treatment with fluoroquinolones may be preferable to clarithromycin. GenoType® HelicoDR test eliminates the need for culture performance and susceptibility tests for several common antibiotic agents and enables optimal and specific antibiotic treatment adjustment. CONCLUSION: We recommend a combination of PCR assay and bacterial culture for a quick method of screening and more efficient identification of H. pylori strains and resistance patterns.

[RESISTANCE OF HELICOBACTER PYLORI TO ANTIBIOTICS IN ISRAEL: PAST VS PRESENT].

INTRODUCTION: Helicobacter Pylori (H. Pylori) is a spiral shaped Gram-negative bacterium which is known to cause chronic gastric inflammation (gastritis) that could develop into a gastric or duodenal ulcer. The standard first line therapy for H. Pylori infection is a 7-14 days period of "triple therapy" consisting of proton pump inhibitors (PPI) and the antibiotics clarithromycin and amoxicillin or metronidazole. Recently there has been an increase in H. Pylori resistance to antibiotic treatment. Throughout the years 1999, 2002, 2010, 2013 and 2014 studies have been conducted in Israel that examined H. Pylori resistance rates for commonly used antibiotics. These studies included 40-138 participants who were diagnosed with infection caused by H. Pylori. Based on information derived from these studies, there is a clear increase in H. Pylori resistance to antibiotics, particularly to tetracycline, amoxicillin and clarithromycin.

Association of Streptococcus bovis presence in colonic content with advanced colonic lesion.

AIM: To prospectively examine the association between presence of Streptococcus bovis (S. bovis) in colonic suction fluid and the endoscopic findings on colonoscopy. METHODS: From May 2012 to March 2013, 203 consecutive patients who underwent colonoscopy for any reason were enrolled in the study. Exclusion criteria included: antibiotic use in the previous month, age younger than 18 years, and inadequate preparation for colonoscopy. The colonoscopy was performed for the total length of the colon or to the occluding tumor. The endoscopic findings were registered. Samples were obtained proximal to the colonoscopic part of the suction tube from each patient and sent to the clinical microbiology laboratory for isolation and identification of S. bovis. Samples were incubated in enrichment media with addition of antibiotic disks for inhibition of growth of Gram-negative rods. The samples were seeded on differential growth media; suspected positive colonies were isolated and identified with Gram staining, catalase, and pyrrolidonyl arylamidase tests, and further identified using a VITEK2 system. Statistical analyses were performed using the Student's t and χ(2) tests. RESULTS: Of the 203 patients recruited, 49 (24%) patients were found to be S. bovis carriers; of them, the endoscopic findings included: 17 (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6 (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7 (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram-positive coccus) is considered part of the normal intestinal flora. There is an association between S. bovis bacteremia and colonic neoplasia. It is not well understood whether the bacterium has a pathogenetic role in the development of neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a clear relationship between positivity for S. bovis in colonic suction fluid and findings of malignant tumors and large polyps in the colon. CONCLUSION: There is an association between S. bovis bacteremia and malignant colonic lesions; this should prompt for development of a reliable screening method for advanced colonic lesions.

Improvement and optimization of the classical gastric biopsy culture technique for Helicobacter pylori diagnosis using trypsin.

Helicobacter pylori infection represents a key factor in the aetiology of various gastrointestinal diseases. H. pylori infection diagnosis is generally achieved using both invasive (e.g. biopsy of the gastric epithelium) and non-invasive methods. Therefore, cultivation on a growth medium becomes complex. Trypsin is a proteinase enzyme that plays a role in an early stage of tissue digestion. In this study, we used trypsin in order to improve the diagnostic sensitivity of the H. pylori cultivation technique. We used 46 duplicate antrum biopsy specimens, divided into trypsin-treated and non-treated groups. The tissues were seeded on a selective H. pylori growth agar medium. We demonstrated that the classic H. pylori culture technique misses the growth of a large number of H. pylori colonies. Significantly more colonies were found in the trypsin-treated specimens group.

An efficiency comparison between three invasive methods for the diagnosis of Helicobacter pylori infections: Culture from stomach biopsy, rapid urease test (CUTest(®)), and histologic examination of gastric biopsy.

BACKGROUND: Helicobacter pylori is one of the most prevalent pathogenic bacteria in the world, and humans are its principal reservoir. There are several available methods to diagnose H. pylori infection. Disagreement exists as to the best and most efficient method for diagnosis. METHODS: In this paper, we report the results of a comparison between three invasive methods for H. pylori diagnosis among 193 patients: culture, biopsy for histologic examination, and rapid urease test (CUTest(®)). RESULTS: We found that all three methods have a high sensitivity and specificity for the diagnosis of infections caused by H. pylori. However, the culture method, which is not used routinely, also showed high sensitivity, probably due to biopsies' seeding within 30 minutes, using warm culture media, non-selective media, and longer incubation. CONCLUSIONS: Although not a routine test, culture from biopsy can be meaningful in identification of antibiotic-resistant strains of H. pylori and should therefore be considered a useful diagnostic tool.

Susceptibility of Helicobacter pylori to Levofloxacin and Rifampicin in Israel.

The aim of this study was to assess the resistance level of Helicobacter pylori to levofloxacin and rifampicin from samples collected from pediatric and adult Israeli patients from 2012 to 2013. A total of 117 isolate samples of H. pylori were collected between 2012 and 2013. Isolates were cultured from stomach antrum biopsies and identified by the microbiology laboratory. Isolates were considered susceptible to levofloxacin and rifampicin by an Etest. Out of 117 isolates, 105 were found susceptible and 12 resistant to levofloxacin. For rifampicin, 104 isolates were susceptible and 13 were resistant. Study results estimate an alarming resistance rate, which reiterates the need for prudent use of alternative antibiotics to prevent further spread of resistant strains. Therefore, we suggest subjecting cultures from biopsy samples to susceptibility testing for the purpose of identification of strains resistant to levofloxacin and rifampicin among other antibiotic agents. This will allow for successful monitoring of microbial resistance and will assure prudent use of antimicrobial modalities.

Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19-79 years) and 76 from children (7-17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

Endothelial dysfunction is reversible in Helicobacter pylori-positive subjects.

BACKGROUND: Studies have shown an association between Helicobacter pylori (HP) infection and atherosclerosis. Although epidemiological studies have suggested an association between HP infection and atherosclerosis, the issue is still controversial. It is not clear whether HP eradication will reverse endothelial damage and prevent cardiovascular events. METHODS: Thirty-one dyspeptic subjects (16 men, 15 women; 50.8 ± 16.7 years) were diagnosed as HP positive using histopathological evaluation. Eleven dyspeptic subjects (5 men, 6 women; 55.4 ± 9.3 years) were negative to HP (controls). Interleukin-6 level and vascular measurements (ankle brachial index and flow-mediated diameter percent change) were done twice: on entry and 3 months afterwards. HP-positive subjects were treated with the triple therapy. RESULTS: Thirty-one HP-positive subjects (50.8 ± 16.7 years, 16 men, weight 79.6 ± 14.8 kg, height 1.70 ± 0.1 m, body mass index [BMI] 27.5 ± 4.4, waist circumference 97.6 ± 16.7 cm) were treated accordingly. There were 11 HP-negative subjects (controls) (55.4 ± 9.3 years, 5 men, weight 83.4 ± 16.8 kg, height 1.68 ± 0.1 m, BMI 29.6 ± 6.1, waist circumference 104.4 ± 13.7 cm). No difference in age (P=.27), weight (P=.51), height (P=.50), BMI (P=.30), or waist circumference (P=.20) was observed. HP-positive subjects had severe endothelial dysfunction (-1.26 ± 8.4%) that improved after treatment (8.4 ± 9.0%) (P=.001). HP-negative subjects had endothelial dysfunction (1.9 ± 9.7%) that was not improved (5.6 ± 8.3%) (P=.41). Interleukin-6 levels in serum were not elevated in HP-positive subjects before or after HP eradication (8.4 ± 17.5 vs 13.5 ± 30.7 pg/mL; P=.45). CONCLUSIONS: The novel finding of our study was that HP eradication can improve endothelial dysfunction.

[Incidence of influenza among patients admitted to the department of internal medicine during the winter season].

BACKGROUND: Influenza is a common disease, especially in the winter season. Influenza virus causes symptoms of acute viral illness, development of complications and worsening of chronic diseases. Vaccination may prevent influenza illness. OBJECTIVES: 1. To determine the rate of vaccination against influenza. Furthermore, in the immunized patients--the study aimed to determine the efficiency of the vaccination. 2. To determine the incidence of influenza illness among patients admitted to a Department of Internal Medicine during the winter season. METHODS: We performed a prospective screening of 124 consecutive patients hospitalized in the Department of Internal Medicine during February 1998. Demographic parameters (age, sex) and admission diagnosis were collected. All patients were asked about influenza vaccination in the last fall. Blood samples were collected on admission and 10-30 days later. Three relevant virus subtypes were examined. Virus subtype was determined in all patients with evidence of influenza illness. RESULTS: Eleven patients (8.9%) were found with evidence of acute influenza illness at the time of hospitalization. The rate of patients with chronic pulmonary disease was higher in this group than in the group without evidence of influenza (p = 0.03). Forty-four out of 124 patients (35.5%) had been vaccinated against influenza. In the vaccinated patients, the protective antibody level for all 3 subtypes developed in 27.3% of cases and for one or two subtypes in 50% of cases. In 22.7% of patients no protective level of antibody was detected for any subtype. CONCLUSIONS: It is necessary to encourage vaccination in the high-risk group patient, especially those with chronic pulmonary disease. It is essential to develop new vaccination strategies and prophylactic antiviral medications.