Haim Shmuely

Relationship between Helicobacter pylori CagA status and colorectal cancer

OBJECTIVES:Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status.METHODS:In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses.RESULTS:H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA− was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7–41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3–1229.2; p = 0.001).CONCLUSIONS:Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Use of the NOW Streptococcus pneumoniae urinary antigen test in cerebrospinal fluid for rapid diagnosis of pneumococcal meningitis

Streptococcus pneumoniae is one of the most common pathogens in bacterial meningitis. Rapid diagnosis is critical for effective treatment. The aim of this study was to assess the accuracy of the NOW S. pneumoniae Urinary Antigen Test, (Binax, Portland, ME, USA) originally developed for urine testing, in detecting the S. pneumoniae antigen in cerebrospinal fluid (CSF). The study included 519 patients with suspected meningitis. CSF, blood and urine samples were cultured according to standard methods. CSF viral culture was also performed. CSF and urine specimens were tested for pneumococcal antigen with the NOW S. pneumoniae test.S. pneumoniae was isolated from the CSF of 22 patients. The direct antigen test was positive in CSF in 21/22 patients (95.4% sensitivity), and in urine, in 12/21 (57.1% sensitivity). Direct CSF smear was positive in 15/22 (68% sensitivity). CSF samples that cultured negative for S. pneumoniae (n = 470) or positive for other bacteria (n = 27) were also negative on the NOW test (100% specificity). By contrast, urine samples of 63/470 of patients with negative CSF culture were positive on the NOW test, as were 5/27 urine samples of patients with CSF culture positive for other bacteria (p = 0.45). The NOW S. pneumoniae antigen test in CSF yields a rapid and very reliable diagnosis of pneumococcal meningitis, enabling prompt and adequate treatment. Its low sensitivity in urine indicates that this mode of testing is not useful for the diagnosis of pneumococcal meningitis. These data have been included in the FDA application for approval of the NOW test for use in the CSF for the diagnosis of pneumococcal meningitis.

Role of transesophageal echocardiography in the evaluation of patients with retinal artery occlusion

OBJECTIVE To evaluate the role of transesophageal echocardiography (TEE) in detecting cardiac and thoracic aortic sources of retinal emboli. DESIGN Retrospective observational case series. PARTICIPANTS The study population consisted of 18 patients who were initially seen with retinal artery occlusion (7 central, 11 branch) and underwent TEE as part of the systemic evaluation. INTERVENTION All patients underwent TEE, consisting of complete two-dimensional and Doppler color flow examinations. TEE was done immediately after transthoracic echo (TTE) examination. The medical records were reviewed. MAIN OUTCOME MEASURE Detection of a possible cardiac or thoracic aortic source of retinal embolus. RESULTS Cardiac or thoracic aortic pathologic conditions, which were a possible source of the retinal emboli, were detected by TEE in 13 of the 18 patients (72%). They included aortic arch atheroma (n = 7), mitral annulus calcification (n = 4), left atrial appendage thrombus (n = 2), valvular abnormalities (n = 5), left atrial smoke (n = 3), and patent foramen ovale (n = 3). In 11 patients (61%), at least one cardiac or aortic source of emboli detected by TEE was missed by TTE. Significant carotid artery disease (>or=40% stenosis) was present in 3 of 16 patients (17%). CONCLUSIONS TEE is a potentially useful modality for detecting possible sources of retinal artery emboli and may be considered as an adjunct to the routine evaluation of affected patients.

Helicobacter pylori and Clostridium difficile in Cystic Fibrosis Patients

We describe the prevalence of H. pylori and toxigenic Clostridium difficile (CD) infection and its relationship with gastrointestinal symptoms and pancreatic sufficiency (PS) or insufficiency (PI) in cystic fibrosis (CF) patients. Stool specimens from 30 consecutive patients with CF, aged 1–44, and from 30 healthy similarly aged subjects were tested for the H. pylori antigen by specific monoclonal antibodies and for CD toxins by Tox A/B assay and Tox A assay. CF patients were assessed clinically and tested for specific H. pylori serum antibodies and for mutations. In CF patients, the prevalence of H. pylori antigen was 16.6% (5/30), compared to 30% (9/30) in controls. Of the 26 CF patients with PI, only 2 (7.6%) were infected by H. pylori, compared with 3 of the 4 (75%) patients with PS (P=0.001). H. pylori infection was diagnosed in 3 of 5 (60%) CF patients carrying mild mutations, compared to 1 of 25 (4%) CF patients carrying severe mutations (P=0.01). Fourteen of 30 (46.6%) stool specimens from CF patients tested positive in the ToxA/B assay, and 3 of 14 tested positive for ToxA. No significant differences in antibiotic use, severity of lung disease, PI, chronic abdominal pain, or genotype were found between the two groups. None of the controls was positive for CD toxins. Prevalence of H. pylori infection in CF patients was lower than in similarly aged non-CF controls. CF patients with PI or a history of distal intestinal obstruction syndrome and those carrying mutations associated with a severe phenotype were protected against H. pylori infection. Almost half of the CF patients were asymptomatic carriers of CD producing mostly toxin B. More studies are needed to confirm our results in a larger group of CF patients.

Prediction of mortality in patients with bacteremia : The importance of pre-existing renal insufficiency

Pre-existing renal insufficiency serves as a common risk factor in the development of acute renal failure. Acute renal failure is a common finding in patients with bacteremia and is associated with poor prognosis. A total of 2722 consecutive patients 18 years old or older, fulfilling strike criteria of bacteremia or fungemia were prospectively evaluated to establish the prognostic importance of pre-existing renal insufficiency in bacteremic patients. They were classified according to serum creatinine levels upon admission into three groups. 915 patients had normal creatinine levels (≤ 1.0 mg/dL), 1528 had mild to moderate renal failure (creatinine 1.1–3 mg/dL) and 279 patients had severe renal failure upon admission (creatinine >3.0 mg/dL). Mild to severe renal failure upon admission was associated with old age, male gender, diabetes mellitus, ischemic heat disease, hypertension and congestive heart failure. The serum albumin in patients with severe renal failure was significantly low, with a mean of 2–9 mg/dL. Urinary tract infections were more prevalent in patients with mild to severe renal failure, while intravenous line infections, bacterial endocarditis and soft and skin tissue infections were more common in patients with normal renal function. In the 279 patients with severe renal failure the mortality rate was significantly higher (50%) compared to patents with mild to moderate renal failure and patients with normal renal function (21% and 26% respectively, p = 0.0001). Multiple regression analysis revealed that pre-existing serum creatinine >3 mg/dL was significantly associated with death attributable to bacteremia (OR=1.7, 95% CI 1.0–2.7). In conclusion, adult bacteremic patients with pre-existing serum creatinine above 3 mg/dL upon admission are at increased risk of mortality due to bacteremia than patients with normal or mild to moderate renal failure.

Antibiotic resistance of Helicobacter pylori in Israeli children

Abstract Objectives. To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients. Material and methods. A prospective case-series design was used. The study group included 174 patients aged 1–18 years referred to the Schneider Childrens Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire. Results. Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy. Conclusions. H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.

Association of Helicobacter pylori infection with Shigella gastroenteritis in young children.

OBJECTIVE:Helicobacter pylori infection is acquired mainly in early childhood. Much is unknown about the mode of transmission. The organism can be cultivated from cathartic stools and vomitus and is potentially transmissible during episodes of gastrointestinal tract illness. Because Shigella and Salmonella are common pathogens in enteric infections in children, we examined the association of H. pylori with Shigella and Salmonella infections in pediatric patients.METHODS:The study population included consecutive children aged 2–72 months hospitalized with acute gastroenteritis who had culture-proven shigellosis (N = 78) or salmonellosis (N = 76). Sixty-five healthy similarly aged children with culture-negative stools served as controls. Parents of cases were queried for personal and family characteristics and socioeconomic indicators. The stool specimens from all participants were tested for H. pylori antigen.RESULTS:On univariate analysis, Shigella gastroenteritis was significantly associated with H. pylori positivity (odds ratio, OR: 3.5, 95% confidence interval (CI): 1.5–8.8, P = 0.004) compared to controls. This association remained significant even after adjusting for living conditions, fathers occupation, and fathers education (OR = 3.38, 95% CI: 1.39–8.22, P = 0.007). Salmonella gastroenteritis was not associated with H. pylori positivity (OR = 1.1; 95% CI: 0.4–3.0, P = 0.8).CONCLUSIONS:H. pylori infection in young children is associated with Shigella gastroenteritis. This association warrants further investigation.

Candida tropicalis Multifocal Endophthalmitis as the Only Initial Manifestation of Pacemaker Endocarditis

PURPOSE To document a case of Candida tropicalis endophthalmitis as the only manifestation of pacemaker endocarditis. METHODS We examined a 75-year-old man with diabetes mellitus who was initially examined for bilateral multifocal endophthalmitis complicating endocarditis 2 years after a permanent pacemaker for sick sinus syndrome was implanted. RESULTS Transesophageal echocardiography showed a large vegetation with a 3-cm diameter attached to the pacing electrode in the right ventricle. Six consecutive blood cultures grew C tropicalis. CONCLUSIONS Ocular involvement, including multifocal endophthalmitis, may occur as the only manifestation of C tropicalis endocarditis, complicating an intravenous permanent pacemaker.

Elevated 13C Urea Breath Test Values Females Infected With Helicobacter pylori

Abstract13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a high density and active bacteria and has the potential to provide a noninvasive index of bacterial growth. We describe the gender differences in δ over baseline 13C-UBT values in 7373 patients (4531 females and 2842 males) who underwent 13C-UBT test for the diagnosis of H. pylori infection. A significantly (P<.001) higher mean ± SD excess delta 13CO2 excretion was recorded in females (24.7±17.4) compared to males (17.6±11.8) aged 10–80 years. The age-adjusted difference between sexes was 7.1 (95% confidence interval, 6.4–7.9). Our analysis demonstrates quantitatively for the first time gender associated differences in H. pylori host interaction. This study suggests that infected females have a higher bacterial load and therefore may potentially infect their children at a higher degree than males.

Seven-year study of bacteremia in hospitalized patients on chronic hemodialysis in a single tertiary hospital.

Sixty-seven hospitalized bacteremic patients on chronic hemodialysis were matched with 134 bacteremic controls. Mortality (25% and 28% respectively) was unrelated to dialysis. Predictors of mortality were: advanced age, decreased functional capacity, and malignancies. Most common organisms recovered were Staphylococcus aureus (30%), coagulase negative Staphylococcus (15%), and polymicrobial agents (15%).