Differences between repeated lipid profile measurements in a tertiary hospital over a short time period.

BACKGROUND: Measurement of the plasma lipid profile, mainly low-density lipoprotein cholesterol (LDL-C), is widely used in the management of hospitalized patients as part of their cardiometabolic risk assessment. In common practice, LDL-C is calculated indirectly by the Friedewald equation. For many years, fasting of 8-14 h is needed to obtain an accurate lipid profile measurement, although recent guidelines do not necessitate it. The aim of this study was to find patients with two consecutive LDL-C measurements taken over a short time period on the same admission to see if a significant difference exists and to suggest reasons that may explain it. We also aim to define whether the difference between LDL-C calculated by the Friedewald equation is diminished while using the newer Martin/Hopkins, de Cordova or Sampson/NIH equations. METHODS: This was a retrospective cohort study performed in one medical center in Israel. In a five-year time period, 772 patients with two repeated LDL-C measurements taken on the same admission were found. The median time gap between tests was 2 days. Correlations between laboratory results and LDL-C measurements were determined. RESULTS: A total of 414 patients (53.6%) had a difference greater than the acceptable total error of 8.9% in LDL-C calculation using the Friedewald equation, with a mean 25.8% difference between the two tests. Newer LDL-C calculations showed less diversity. Non-HDL-C was found as the only variable with a major correlation with LDL-C results in all equations. A weaker correlation was found with HDL-C. Triglycerides showed an even weaker correlation, and glucose differences had no correlation with LDL-C differences. CONCLUSIONS: Repeated LDL-C measurements can vary widely, even during a short period of hospitalization. In this study, more than half of the patients had a significant difference between their consecutive LDL-C results. This wide difference between two consecutive tests was diminished using newer calculations, yet not well explained. The fasting state likely has no effect on LDL-C levels. The results of this study might emphasize that many factors influence LDL-C calculation, especially in the disease state. Further research is needed, especially in looking for a more accurate LDL-C calculation from existing formulas.

Immune reconstitution inflammatory syndrome (IRIS) in a patient with neuro pulmonary nocardiosis following hematopoietic cells transplantation (HCT).

Immune reconstitution inflammatory syndrome (IRIS) is increasingly reported in various HIV negative patients with immunosuppression, but the relationship with hematopoietic cell transplantation (HCT) is not well defined. We report a case of IRIS in a patient infected with pulmonary and CNS Nocardiosis following HCT due to primary myelofibrosis.

Teaching During the COVID-19 Pandemic: The Experience of the Faculty of Medicine at the Technion-Israel Institute of Technology.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust. OBJECTIVES: To describe changes in teaching during the first phase of the COVID-19 pandemic. METHODS: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. RESULTS: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. CONCLUSIONS: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

[TEACHING INTERNAL MEDICINE IN THE SHADOW OF THE COVID-19 OUTBREAK - THE EXPERIENCE OF THE TECHNION FACULTY OF MEDICINE].

INTRODUCTION: The clerkship of internal medicine is pursued in the 2nd semester of the 4th year at the Technion Medical School. Following the COVID-19 outbreak, frontal and bedside teaching was interrupted. Therefore, we decided to provide distant teaching until having the opportunity to resume clinical bedside teaching. A team of tutors composed a course of weekly units, each week assigned to a different subject in internal medicine. A total of 120 students were divided into 15 groups of 8 students, each group guided by a personal tutor. The format of each unit included online pretest, clinical virtual cases and two separate 2 hour ZOOM sessions with the tutor. The pretest was based on 1-3 chapters from Harrison's Internal Medicine textbook, 20th edition, and consisted of both clinical reasoning and knowledge questions. During ZOOM sessions with the tutor, the students practiced clinical problem solving. In addition, all the students were granted free access to the commercial "Aquifer" case-based virtual course for more practice. The students' feedback at the end of the learning period revealed that, although frustrated in being away from the clinics, the overall level of satisfaction from the course was good (rated 5 or 4/5 by 65% of responders) and the time was used efficiently. In conclusion, the students received a positive proactive learning experience of both theoretical aspects and clinical reasoning skills in internal medicine. There is no doubt that bedside teaching in medicine is invaluable and can't be replaced by any other means, however, given the circumstances, our format provided a reasonable temporary alternative.

Risk Factors for Low Bone Density in Inflammatory Bowel Disease: Use of Glucocorticoids, Low Body Mass Index, and Smoking.

BACKGROUND: Inflammatory bowel disease (IBD) patients are reported to have lower bone density compared to healthy controls. There is limited consensus regarding factors affecting bone density among these patients. Our aim, therefore, was to determine clinical and genetic variables that contribute to lower bone mineral density (BMD) in IBD patients. METHODS: A cross-sectional study of IBD patients treated in a tertiary referral center was performed. Epidemiological and clinical data were collected, and genetic testing for the common mutations in Nucleotide-binding Oligomerization Domain-containing protein (NOD)2 was performed. We examined correlations between the different variables and BMD in the total hip, femoral neck, and lumbar spine. RESULTS: Eighty-nine patients (49% males, 67 Crohn's disease [CD]) participated in the study. 42Forty-two (63%) of the CD and 13 (59%) of the ulcerative colitis patients met the criteria for osteoporosis/osteopenia. Factors associated with lower Z scores were low body mass index (BMI; r = -0.307, p = 0.005), use of glucocorticoids (likelihood ratio [LR] 5.1, p = 0.028), and a trend for male gender (LR = 3.4, p = 0.079). Among CD patients, low bone density showed borderline significance for association with gastrointestinal surgery (LR = 4.1, p = 0.07) and smoking (LR = 3.58, p = 0.06). Low levels of 25OHD were not associated with low BMD, nor were mutations in NOD2. No increased rate of fractures was seen among patients with osteopenia or osteoporosis. CONCLUSION: In addition to the generally accepted risk factors for osteoporosis (glucocorticoids, low BMI, smoking), male IBD patients had a trend toward lower BMD. Carrying a mutaticon in NOD2 did not confer a risk for bone loss.

Pleural Fluid B-Type Natriuretic Peptide Level as an Additional Indicator for the Fluid's Etiology.

BACKGROUND: The identification of the etiology of a pleural effusion can be difficult. Measurement of serum B-type natriuretic peptide (BNP) levels is helpful in the diagnosis of congestive heart failure (CHF) as a cause of respiratory failure, but pleural fluid BNP measurement is still not part of the workup for pleural effusion. OBJECTIVES: To identify the correlation between pleural fluid BNP levels and clinical diagnosis. METHODS: In this cross-sectional study, data from 107 patients admitted to the department of internal medicine between November 2009 and January 2015 were obtained from medical records. Patients underwent a diagnostic thoracocentesis as part of their evaluation. They were grouped according to final diagnosis at discharge and clinical judgment of the attending physician. RESULTS: Serum BNP levels were significantly higher in the CHF patients compared to patients with non-cardiac causes of pleural effusion (1519.2 and 314.1 respectively, P < 0.0001). Mean pleural fluid BNP was also significantly higher in the CHF patients (1063.2 vs. 208.3, P < 0.0001). Optional cutoff points to distinguish between cardiac and non-cardiac etiology of pleural effusion were 273.4 pg/ml (sensitivity 83.3%, specificity 72.3%, accuracy 76.7%) or 400 pg/ml (sensitivity 78.6%, specificity 86.2%, accuracy 83.0%). A strong correlation was found between serum BNP and pleural fluid BNP levels. CONCLUSIONS: High levels of serum BNP in patients presenting with pleural effusion suggest CHF. In cases with doubt regarding the etiology of pleural effusion, high levels of pleural fluid BNP can support the diagnosis, but are not superior to serum BNP levels.

NOD2/CARD15 Mutations among Bedouin Arabs with Inflammatory Bowel Disease: Frequency and Phenotype Correlation.

BACKGROUND: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD. OBJECTIVES: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype. METHODS: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC. RESULTS: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found. CONCLUSIONS: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.

[THE NATIONAL FINAL INTERNAL MEDICINE EXAMINATION SCORE - IS IT PREDICTABLE?]

INTRODUCTION: There is no current medical licensing examination in Israel (2016). The only objective indicators which reflect students' medical knowledge and basic clinical reasoning skills are the national medical examination scores. The aim of the present study was to investigate the nature of the relationship between students' demography, gender and academic achievements during their pre-clinical studies and their final national internal medicine examination scores. METHODS: The study was based on data collected by the Technion information system. The study cohort consisted of medical students admitted to the Technion Faculty of Medicine over a decade from 2005-2014, via a standard admission procedure. Students accepted on the basis of former academic achievement were not part of this cohort. The cohort was divided into three, based on the level of success in the final national examination in internal medicine. CONCLUSIONS: Our main conclusions were: (1) the admission screening criteria (scores of matriculation and psychometric tests) are helpful markers for predicting success in the final examination in internal medicine; (2) students who performed the psychometric tests in the Arabic language have relatively lower-achieving grades in the final examination in internal medicine in comparison to students taking the same psychometric exam in the Hebrew language. Furthermore, (3) high achievements in core preclinical courses and especially in the "integrative course" in the first 2 trimesters of the fourth year of studies are relatively strong predictors for success in the final examination in internal medicine.

[REDUCTION OF ANTIBIOTIC CONSUMPTION IN RAMBAM HEALTH CARE CAMPUS - THE ROLE OF AN ANTIBIOTIC STEWARDSHIP PROGRAM].

INTRODUCTION: Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs. AIMS: To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide. METHODS: Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards. RESULTS: Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments. CONCLUSIONS: Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Rac1 Polymorphisms and Thiopurine Efficacy in Children With Inflammatory Bowel Disease.

OBJECTIVES: Thiopurines are effective for maintenance of remission in inflammatory bowel disease (IBD) in only about half of patients. Predictors of response may assist in selecting the most appropriate patients for thiopurine therapy. Thiopurines inhibit Rac1, a GTPase that exerts an antiapoptotic effect on T-lymphocytes. A genetic association was recently demonstrated between a Rac1 single nucleotide polymorphism (SNP) and poorer response to thiopurines in adult patients with Crohn disease. We aimed to determine whether Rac1 SNPs are associated with response to thiopurines in children with IBD. METHODS: Children with IBD treated with thiopurines were prospectively followed for 1 year and were genotyped for 3 Rac1 SNPs previously found to be relevant to IBD: rs10951982, rs4720672, and rs34932801. The rate of sustained steroid-free remission (SSFR) without treatment escalation by 12 months was compared between wild types (WTs) and heterozygotes. RESULTS: A total of 59 patients were studied (63% boys, 80% having Crohn disease, mean age 13 ±â€Š4.1). Nineteen of the 41 WT (46%) and 9 of the 15 (60%) heterozygotes for rs10951982 were in SSFR (P = 0.55). Similarly, 21 of the 45 (47%) WT and 8 of the 12 (67%) heterozygotes for rs4720672 were in remission (P = 0.33). Finally, 21 of the 45 (47%) WT and 3 of the 5 (60%) heterozygotes for rs34932801 were in remission (P = 0.66). All of the 3 comparisons remained nonsignificant in a sensitivity analysis of only the patients with Crohn disease. CONCLUSIONS: We did not find an association between 3 Rac1 SNPs and thiopurine effectiveness by 12 months in a prospective study of children with IBD. Other predictors of response should be sought to optimize patient selection for thiopurine therapy.

A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10⁻9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10⁻8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10⁻8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10⁻9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.

Hospital Care Efficiency - Measuring Lipid Profile During Hospitalization.

Background: Lipid profile measurement in order to identify patients with elevated low-density lipoprotein cholesterol (LDL-C) is clearly recommended for all age groups. However, the value of screening patients for elevated LDL-C during hospitalization has not been determined. The aim of this study was to investigate the value of lipid screening tests in patients admitted to internal medicine wards, and as part of our efforts to promote a more intelligent and efficient use of laboratory and imaging tests during hospital care. Methods: We conducted this retrospective, observational study, in which medical charts of patients for whom at least one lipid profile measurement was performed during hospitalization were reviewed. The patients were categorized into 5 groups according to admission diagnosis, and for each patient, we looked if the lipid profile was mentioned or referred to, based on guidelines, in the discharge summary. Results: Lipid profile taken during hospitalization was referred to in the discharge letter in only 38.7% of patients, and even in the case of a need to consider according to guidelines, only a 45.7% consideration rate was found. Conclusion: This study highlights the need for a more efficient and focused approach to the use of lipid profile measurement during hospitalization.

Non-Jewish Israeli IBD patients have significantly higher glutathione S-transferase GSTT1-null frequency.

BACKGROUND: The involvement of oxidant/antioxidant imbalance in the development of inflammatory bowel disease (IBD) is well documented. Two members of the glutathione S-transferase (GST) family of enzymes, GSTM1 and GSTT1, known to take part in cellular protection against electrophiles, demonstrate common deletion variants (termed null) associated with impaired enzyme function. AIM: To evaluate the effect of GSTM1/GSTT1 genotype on IBD susceptibility in a Israeli cohort and to study the correlation between GSTM1/GSTT1 genotype, smoking status, and a variety of clinical characteristics of IBD. METHODS: A cohort of 606 Israeli IBD patients (453 with Crohn's disease [CD] and 153 with ulcerative colitis [UC]) and 528 ethnically matched healthy controls were genotyped for the null variants of GSTM1 and GSTT1. In patients, phenotype-genotype correlations were examined. RESULTS: Ethnic stratification of healthy controls revealed a higher frequency of GSTT1-null in Jewish and Arab Moslem individuals compared to Druze individuals (P < 0.0005), but no difference in GSTM1-null was found. Comparing IBD patients (both CD and UC) to healthy controls revealed a pattern of lower GSTM1-null and higher GSTT1-null frequencies, which reached significance in Arab Moslem patients. No association was found between NOD2/CARD15 mutation carriage and GSTM1/GSTT1 genotype. No statistically significant association was found between GSTT1-null or GSTM1-null, smoking status, and other phenotypes of CD/UC. CONCLUSIONS: GSTT1-null appears to be associated with IBD, while GSTM1-null appears to be conversely associated with IBD. No association was found between GSTT1-null or GSTM1-null and specific IBD phenotypes.

Early-onset Crohn disease is associated with male sex and a polymorphism in the IL-6 promoter.

AIMS: Pediatric onset of Crohn disease (CD) is characterized by male sex predominance while adult-onset disease demonstrates female sex predominance. It has been postulated that this phenomenon may be genetically determined or due to an effect of estrogen on age of onset. Interleukin (IL)-6 modulates the TH17 pathway, and the IL-6 promoter is modulated by estrogen, possibly linking genetically determined inflammation and the presence of estrogen. The aim of our study was to investigate whether differences in IL-6 promoter genotype could explain male sex in earlier disease onset. PATIENTS AND METHODS: We genotyped 333 patients with CD and 100 controls, 162 pediatric-onset patients (age of onset 18 years and younger) for the IL-6-174 polymorphic site. Genotype, sex, and age of onset were compared. RESULTS: Males with IL-6-174GG genotype (the wild-type allele) had an increased risk for a younger age of onset compared to males with IL-6-174GC or CC genotype (G --> C genotype), hazard ratio (HR) 1.49, P = 0.02, 95% confidence interval (CI) 1.07-2.09. Females with GG genotype were not found to have an increased risk for a younger age of onset compared with females with G --> C genotype, HR 1.01, P = 0.96, 95% CI 0.72-1.41. CONCLUSIONS: Males with IL-6-174GG genotype are prone to develop CD at a younger age than males with the IL-6-174G --> C genotype. Our study suggests that age of onset may be modified by the IL-6-174GG genotype and this modification is sex dependent. This may be due to increased transcription of IL-6, an effect that may be repressed by estrogen in females.

Disease behavior in children with Crohn's disease: the effect of disease duration, ethnicity, genotype, and phenotype.

BACKGROUND: Disease behavior in Crohn's disease (CD) may be modified by disease location and genotype. Disease behavior may change over time, and thus analysis requires follow-up. To date, there have been few pediatric studies that have evaluated the association between disease behavior and genotype with prolonged follow-up. The aim of our study was to evaluate the effect of genotype, phenotype, and ethnicity on disease behavior in pediatric CD. METHODS: Evaluation of 128 pediatric CD was followed by analysis of 232 pediatric and adult-onset CD patients. Inclusion required at least 2 years of follow-up. Phenotype, ethnicity, and disease duration were recorded. Patients were genotyped for polymorphisms in the NOD2/CARD15 gene. RESULTS: Colonic involvement was more frequent in younger patients. Pediatric disease at end of follow-up was classified as inflammatory (78%), penetrating (7%), and stricturing (17%). Duration of follow-up (mean 4.9 pediatric and 6.4 years mixed) was associated with more stricturing and penetrating disease. There was no association between mean age of onset and NOD2/CARD15, or either of these with disease behavior. These observations were replicated in the mixed cohort. Sephardic Jewish origin was inversely correlated with inflammatory behavior (P = 0.006), independent of NOD2/CARD15 genotype. CONCLUSIONS: Duration of disease and ethnicity, irrespective of NOD2/CARD15 genotype and age of onset, were the only predictors for penetrating or stricturing disease.

Normal body mass index (BMI) can rule out metabolic syndrome: An Israeli cohort study.

The aim of the study was to assess whether body mass index (BMI) can be used as a simple and reliable survey test for metabolic syndrome.The study is an observational cohort study among patients who visited the Rambam Periodic Examinations Institute (RPEI). We analyzed the correlation between obesity indices and presence of metabolic syndrome. We identified the ideal value of BMI for identification of patients at risk for metabolic syndrome. We also described the correlation between different BMI values and its negative predictive value (NPV) for metabolic syndrome.During the study years, 23,993 patients visited the RPEI, and 12.5% of them fulfilled the criteria for metabolic syndrome. Women with metabolic syndrome had higher proportion of obesity, when compared with men (89.9% vs 52.6%; P < .0001). Normal BMI had very high NPV to rule out metabolic syndrome among men and women (98% and 96%, respectively). Using receiver-operating characteristic curve, we found BMI 27 to be the ideal value for identification of metabolic syndrome for the entire cohort (area under the curve [AUC] 0.767, 95% confidence interval [CI] 0.758-0.775, P < .0001), for men (AUC 0.726, 95% CI 0.715-0.738, P < .0001), and for women (AUC 0.843, 95% CI 0.831-0.855, P < .0001). BMI below 30 provided NPV of 91.1% to rule out metabolic syndrome.The BMI as single survey measurement of obesity offers high NPV for metabolic syndrome and can be used by physician and patients for this purpose.

Relative fat mass is a better predictor of dyslipidemia and metabolic syndrome than body mass index.

Relative fat mass (RFM) had been recently developed. We aimed to examine RFM predictability to various cardiometabolic risk factors, compared to BMI. METHODS: Observational, cohort study, among patients who visited the Rambam Periodic Examinations Institute (RPEI). We compared the correlation of BMI and RFM to hypertension, impaired fasting glucose, high LDL, low HDL and metabolic syndrome, by gender. RESULTS: During study years, 20 167 patients visited the RPEI and included in the trial. Compared to BMI, RFM showed significantly better predictability (odds ratio [OR], [95% confidence interval (CI), P value]) of high LDL [1.618 (1.441-1.816, P < 0.001) vs. 0.732 (0.67-0.8, P < 0.001) in men; 1.572 (1.377-1.794, P < 0.001) vs. 0.938 (0.849-1.163, P = 0.94) in women], low HDL [2.944 (2.569-3.373, P < 0.001) vs. 2.177 (2-2.369, P < 0.001) in men, 2.947 (2.519-3.448, P < 0.001) vs. 1.9 (1.658-2.176, P < 0.001) in women], high triglycerides [4.019 (3.332-4.847, P < 0.001) vs. 1.994 (1.823-2.181, P < 0.001) in men, 3.93 (2.943-5.247, P < 0.001) vs. 2.24 (1.887-2.62, P < 0.001) in women] and metabolic syndrome [7.479, (4.876-11.47, P < 0.001) vs. 3.263 (2.944-3.616, P < 0.001) in men, 16.247 (8.348-31.619, P < 0.001) vs. 5.995 (5.099-7.048, P < 0.001) in women]. There was no significant difference in the predictability of BMI and RFM to hypertension and diabetes mellitus. CONCLUSION: RFM provides high predictability for dyslipidemias and metabolic syndrome.

Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility.

BACKGROUND: Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon. METHODS: We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location. RESULTS: We found an age-related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first-decade onset patients (P = 4.57 x 10(-5), odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72-4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset. CONCLUSIONS: In early-onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early-onset disease.

Evaluation of the interleukin-23 receptor gene coding variant R381Q in pediatric and adult Crohn disease.

BACKGROUND: Pediatric-onset Crohn disease (CD) may differ in genotype or phenotype from adult-onset CD. Genome-wide screening recently identified a protective mutation (R381Q) in the interleukin-23 (IL-23) receptor gene located on chromosome 1. The aims of our study were to evaluate whether this mutation is associated with CD in our population and to find whether it may have an impact on age of onset or a specific location phenotype in a pediatric- and adult-onset CD population. PATIENTS AND METHODS: A total of 438 individuals (143 with pediatric-onset CD [age <18 years], 139 with adult-onset CD, and 157 control subjects) evaluated for age at onset and disease location were genotyped for the R381Q mutation in the IL-23 receptor gene by pyrosequencing. RESULTS: Mutant allele incidences were 5.7% in the normal cohort and only 2.28% in the CD cohort (P = 0.01). Carriers were found to constitute 8.9% of the normal cohort and only 4.6% of the CD cohort (P = 0.029). Homozygotes were found in only the control cohort. The mean age of onset for all of the patients with the mutation (including both age groups) was 17.8 +/- 6.1 years versus 21.3 +/- 12.4 years for patients without the mutation (P =0.08). The mutation was not associated with differences in sex, site of disease, or ethnicity. We did not find evidence of allelic interaction with CARD15. CONCLUSIONS: We confirmed the findings that the IL-23 receptor gene coding variant allele R381Q appears to decrease susceptibility to CD in an Israeli Jewish population. We found a trend toward earlier age of onset, but no interactions with CARD15 or modifying effect on disease location.

Guaiac faecal occult blood screening in individuals younger than 50 years of age.

To determine the effectiveness of guaiac faecal occult blood tests (gFOBT) in the early detection of colorectal cancer (CRC) within a population of asymptomatic individuals who attended general periodic examinations, and to suggest the recommended age for this screening tool, the electronic database of the periodic examination institute of Rambam Healthcare Campus for the years 2004-2013 was reviewed. Individuals with positive gFOBT results were interviewed for further workup. Proportions of individuals for whom a polyp or CRC was detected were evaluated according to sex and age. 18 858 individuals were examined during the study period, mean age 48 years. The overall gFOBT uptake was 40.8%. Uptake was significantly higher among men and increased with age. Positive gFOBT was detected in 105 individuals (1.4%). The proportion of positive gFOBT was significantly lower among individuals aged 30-50 years than those older than 50 years of age (1.1 and 1.7%, respectively, P=0.005). No positive gFOBT was detected among individuals younger than 30 years of age. Positive gFOBT was higher in men than in women: 1.8 and 0.9% respectively (P=0.002). CRC was detected in six individuals, including two younger than 50 years of age. Polyps were detected in 15 individuals; of these, four were younger than 50 years of age. In the gFOBT-positive group, proportions of polyps and CRC were the same for subgroups according to age. The findings support consideration of annual gFOBT screening from the age of 40 years.