Israel Medical Association Journal

Abstract

Background: The impact of admission glycated hemoglobin (HbA1c) on hospital outcome is controversial.

Objectives: To evaluate the association between admission glucose and HbA1c levels and mortality 1 year after hospitalization in the internal medicine ward.

Methods: HbA1c level of consecutive patients was measured during the first 24 hours of admission to the internal medicine ward and divided at the cutoff point of 6.5%. Three groups of patients were prospectively identified: patients with preexisting diabetes mellitus (DM), patients with glucose > 140 mg/dl (hyperglycemia) on admission and no known diabetes (H), and patients without diabetes or hyperglycemia (NDM). The primary end-point was 1 year all-cause mortality.

Results: A total of 1024 patients were enrolled, 592 (57.8%) belonged to the DM group, 119 (11.6%) to the H group and 313 (30.6%) to the NDM group. At 1 year, death occurred in 70 (11.9%) in the DM group, 12 (10.0%) in the H group and 15 (4.8%) in the NDM group (P = 0.002). Elevated admission glucose levels did not influence outcome in any of the groups. HbA1c levels were similar for survivors and non-survivors (P = 0.60). Within-group multivariate analysis adjusted for comorbidities and age showed that in the H group HbA1C levels of 6.5% or above were associated with increased mortality risk [hazard ratio (HR) 8.25, 95% confidence interval (CI) 1.93–35.21). In the DM group, HbA1c levels below 6.5% were associated with increased mortality risk (HR = 2.05, 95%CI 1.25–3.36).

Conclusions: Glucose levels upon admission did not affect mortality. However, HbA1c levels below 6.5% had opposite effects on 1 year mortality in diabetes patients and patients with hyperglycemia.

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Abstract

Background: Only a few studies have compared the accuracy of magnetic resonance enterography (MRE) and computed tomography enterography (CTE) in the diagnosis of Crohn's disease and its complications.

Objectives: To compare the sensitivity of MRE and CTE analysis in their ability to detect, sign-by-sign, 10 classical imaging signs of Crohn's disease.

Methods: The study group comprised 42 biopsy-proven Crohn's disease patients who underwent both CTE and MRE within an average period of 6 weeks. Agreement between the two modalities in detecting the 10 most significant radiological signs of CD was evaluated using the Kappa index. The sensitivity of MRE and CTE was calculated using a standard of reference composed of all the findings seen by CTE and/or MRE. We analyzed MRE and CTE sensitivity separately in two groups, according to the time interval between the examinations.

Results: Agreement between CTE and MRE was more than 70% in 8 of the 10 signs: mural thickening, phlegmon, stenosis, skip lesions, mucosal stratification, fistula, abscess, and creeping fat. The Kappa level of agreement values for CTE versus MRE varied between substantial for phlegmon and skip lesions; moderate for fistula, creeping fat, abscess and mural thickening; and fair for stenosis and dilatation. CTE detected more findings than MRE, except for creeping fat and fistula. There was no significant difference in the sensitivity of CTE and MRE in the two groups defined by the time interval (time < 1.5 and time > 1.5 months) except for detection of dilatation.

Conclusions: Almost all imaging signs of Crohn's disease were detected equally well by both modalities regardless of the time interval between examinations. We therefore consider MRE to be reliable for imaging and follow-up in patients with Crohn's disease who may need recurrent imaging.

Abstract

Background: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.

Objective: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.

Methods: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006–June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.

Results: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.

Conclusions: HHV6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Abstract

Background: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF.

Objectives: To evaluate ANS function in colchicine non-responders by using the HRV tool.

Methods: The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls.

Results: No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters.

Conclusions: Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults. 

Abstract:

Background: Waterpipe tobacco smoking (WTS) is common in some populations and may add increased risk for tobaccorelated diseases.

Objectives: To assess the rates of WTS and risk practices associated with WTS in three distinct populations in Israel: long-term Jewish residents (LTJR), immigrants from the former Soviet Union (fSU), and Arabs.

Methods: We conducted a cross-sectional survey of 899 randomly selected participants, age 30–65 years, using face-toface interviews with subjects from the three population groups in Israel. Respondents reported WTS, cigarette smoking, alcohol consumption, and socioeconomic characteristics.

Results: Among men, WTS at least once a week was reported by 4.8% of LTJR, 3.2% of fSU immigrants and 20.3% of Arabs. Lower rates were reported among women of all groups. The younger, less educated men and the younger unmarried women had higher odds of WTS. LTJR who smoked cigarettes and drank alcohol had higher odds of WTS [odds ratio (OR) 32.6, confidence interval (CI) 9.36–113.6; OR = 3.57, CI =1.48–8.63, respectively], compared to non-smokers and non-drinkers. fSU immigrants who smoked cigarettes had higher odds of WTS (OR = 3.40, CI = 0.99–11.7) compared to non-smokers. Among Arabs, cigarette smoking and alcohol consumption were not associated with WTS.

Conclusions: Arabs are more likely than other Israeli populations to engage in WTS. This behavior may add to increased inequalities in rates of tobacco-induced diseases between Arabs and Jews in Israel. Including WTS in the policies for smoke-free public places is called for.

Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. 

Objectives: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not.

Methods: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods.

Results: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. 

Conclusions: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment. 

 

Background: The number of patients awaiting organ transplantation continues to exceed the number of available organs. 

Objectives: To document changes in the demographic characteristics of brain-dead, heart-beating organ donors over the past 10 years which may impact on organ utilization. 

Methods: Data were extracted from the Israel Transplant Registry and the Donor Action database for the 10 year period 2004–2013, inclusive. 

Results: The median age of the donors increased from 44 (range 3–73 years) to 53.5 years (range 1–79 years) (P < 0.001). There was a significant increase in the median age of donors of kidney (33 to 51 years, P < 0.001), liver (41 to 53 years, P < 0.001) and lung (40 to 49.5 years, P < 0.001). The number of donors dying from trauma decreased (34.5% to 20%, P < 0.001), while those with anoxic brain damage increased (14.5% to 25%, P < 0.001). The percent of male donors decreased over the study period, from 63% to 53%. An increase was noted in the mean number of organs transplanted per donor, from 3.29 to 3.82 per donor, due mainly to a significant increase in the utilization of lungs (31.5% to 51.3%, P < 0.001) and livers (76.3% to 82.4%, P < 0.001) while heart utilization decreased significantly since 2006 (40.9% to 17.5%, P < 0.001). 

Conclusion: Trends in the heart-beating, brain-dead organ donor pool in Israel over the past 10 years reveal significant changes in demographic characteristics which in the future will impact on the number of organs available for transplantation. 

 

Abstract

Background: Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular heart disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism.

Objectives: To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors.   

Methods: We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940–1945 in Europe ('exposed', n=653) or in Israel to Europe-born parents ('non-exposed', n=433). Data on socio-demographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups.

Results: The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14).

Conclusions: The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the ‘second generation’ is also raised.

Abstract

Background: A single self-rated health (SRH) assessment is associated with clinical outcome and mortality, but the biological process linking SRH with immune status remains incompletely understood.

Objectives: To examine the association between SRH and inflammation in apparently healthy individuals.

Methods: Our analysis included 13,773 apparently healthy individuals attending the Tel Aviv Sourasky Medical Center for periodic health examinations. Estimated marginal means of the inflammation-sensitive biomarkers [i.e., highly sensitive C-reactive protein (hs-CRP) and fibrinogen] for the different SRH groups were calculated and adjusted for multiple potential confounders including risk factors, health behavior, socioeconomic status, and coexistent depression.

Results: The group with the lowest SRH had a significantly higher atherothrombotic profile and significantly higher concentrations of all inflammation-sensitive biomarkers in both genders. Hs-CRP was found to differ significantly between SRH groups in both genders even after gradual adjustments for all potential confounders. Fibrinogen differs significantly according to SRH in males only, with low absolute value differences.

Conclusions: A valid association exists for apparently healthy individuals of both genders between inflammation-sensitive biomarker levels and SRH categories, especially when comparing levels of hs-CRP. Our findings underscore the importance of assessing SRH and treating it like other markers of poor health.

Abstract

Background: The mass influx of immigrants from tuberculosis-endemic countries into Israel was followed by a considerable increase in the incidence of tuberculosis (TB). All contacts of active TB patients are obliged to be screened by tuberculin skin tests (TST) and, if found positive, prophylactic treatment is considered.

Objectives: To assess the utility of interferon-gamma (IFNγ)-release assay with a prolonged follow-up in preventing unnecessary anti-TB therapy in individuals with suspected false positive results.

Methods: Between 2008 and 2012 the QuantiFERON TB gold-in-tube test (QFT-G) was performed in 278 sequential individuals who were mostly TST-positive and/or were in contact with an active TB patient. In all, whole blood was examined by the IFNγ-release assay. We correlated the TST diameter with the QFT-G assay and followed those patients with a negative assay.

Results: The QFT-G test was positive in only 72 (42%) of all 171 TST-positive individuals. There was no correlation between the diameter of TST and QFT-G positivity. Follow-up over 5 years was available in 128 (62%) of all QFT-G-negative individuals. All remained well and none developed active TB.

Conclusions: A negative QFT-G test may obviate the need for anti-TB therapy in more than half of those with a positive TST.