Israel Medical Association Journal

Background: Pulmonary rehabilitation has shown significant benefit for patients with chronic obstructive pulmonary disease (COPD). The effect on non-COPD pulmonary patients is less well established.

Objectives: To determine whether pulmonary rehabilitation is also beneficial for non-COPD pulmonary patients.

Methods: Clinical and demographic data on non-COPD pulmonary patients who participated in our institutional pulmonary rehabilitation program between January 2009 and December 2016 were collected. Participants engaged in a 60-minute, twice-weekly, ambulatory hospital-based program lasting 12 to 24 sessions. Sessions included both endurance and muscle training as well as healthy lifestyle educational activities. The six-minute walk test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) were conducted before and after the rehabilitation program.

Result: We recruited 214 non-COPD patients, of whom 153 completed at least 12 sessions. Of these, 59 presented with interstitial lung disease (ILD), 18 with non-ILD restrictive lung defects, 25 with asthma, 30 with lung cancer, and 21 with other conditions (e.g., pulmonary hypertension, bronchiectasis) The groups demonstrated significant improvement in 6MWT and in SGRQ scores. Non-COPD patients gained a 61.9 meter (19%) improvement in the 6MWT (P < 0.0001) and 8.3 point reduction in their SGRQ score (P < 0.0001).

Conclusions: Pulmonary rehabilitation is effective in non-COPD pulmonary patients. As such, it should be an integral part of the treatment armament provided to the vast majority of those suffering from chronic respiratory disease.

Throughout history, studies on episodes of famine have led to the discovery of metabolic abnormalities and hormonal aberrations as well as an increased incidence of cancer and mental health conditions. Starvation during early life is thought to nfluence the programming of childhood and adult bone metabolism, which may result in poor bone health in later life. This observational case series includes a small group (with no control group) of famine-exposed Holocaust survivors and their descendants. We proposed an investigational mechanism to determine any association between starvation and osteoporosis, both in the individual survivors and in their descendants.

Background: Reports of longevity in Holocaust survivors (HS) conflict with excess prevalence of chronic diseases described among them. However, data on their long-term risk of cardiovascular diseases (CVD) are limited. Clinical data on large representative groups of HS who were exposed to severe persecution are also limited.

Objectives: To determine the prevalence of CVD and the risk factors in a large cohort of elderly HS compared to elderly individuals who were not exposed to the Holocaust (NHS).

Methods: CVD prevalence rates and risk factors data from the computerized system of the central district of Clalit Health Services, the largest Israeli health maintenance organization (HMO) in Israel were evaluated in a retrospective observational study. The study was comprised of 4004 elderly HS who underwent direct severe persecution. They were randomly matched by identification numbers to 4004 elderly NHS.

Results: HS were older than NHS and 51% of them were older than 85 years. The prevalence rate of ischemic heart disease (IHD) was significantly higher among HS. HS underwent significantly more cardiac interventions (20% vs. 15.7%, P < 0.05). HS status was an independent risk factor for increased IHD and for more coronary interventions.

Conclusions: Despite having a higher prevalence of CVD, a substantial number of HS live long lives. This finding may imply both unique resilience and ability to cope with chronic illness of the survivors as well as adjusted medical services for this population. These findings may help in planning the treatment of other mass trauma survivors.

Background: Temporal trends in the incidence of inflammatory bowel disease (IBD) in the Arab and Jewish populations in Israel have been poorly described.

Objectives: To compare the annual incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in the Arab and Jewish populations in Israel between the years 2003 and 2008.

Methods: We applied a common case identification algorithm to the Clalit Health Services database to both determine trends in age-adjusted incidence and prevalence rates for IBD in both populations during this period and estimate the burden of IBD in Israel.

Results: The incidence of CD in the Arab population increased from 3.1/100,000 in 2003 to 10.6/100,000 person-years in 2008, compared with a decrease in the Jewish population from 14.3/100,000 to 11.7/100,000 person-years for the same period. The incidence of UC in the Arab population increased from 4.1/100,000 in 2003 to 5.0/100,000 person-years in 2008, a low but stable rate, compared with a decrease from 16.4/100,000 to 9.5/100,000 person-years for the same time period in the Jewish population. The prevalence of both diseases increased due to the accumulation of incident cases but remained much lower among Arabs.

Conclusions: Understanding the factors underlying the differences in incidence and prevalence of IBD in the Jewish and Arab populations may shed light on the genetic and environmental factors associated with these diseases.

Background: Rheumatic mitral stenosis (MS) is a relatively rare diagnosis in the developed countries and its treatment during pregnancy is challenging due to hemodynamic changes. With the demographic changes due to recent waves of immigration an increase in the prevalence of rheumatic heart disease is expected.

Objective: To evaluate maternal and neonatal complications in patients with mitral stenosis.

Methods: During the years 2006–2017, 22 women who underwent 31 pregnancies were followed at the Sheba Medical Center in Israel. We collected on regarding hemodynamic changes and their clinical course. MS was classified as mild, moderate, or severe according to mitral valve area by echocardiography. Maternal and fetal adverse events were evaluated according to severity of MS and compared by Poisson regression modeling.

Results: MS was severe in 7 pregnancies (22.6%), moderate in 9 (29%), and mild in 15 (48.4%). Twenty patients were managed conservatively and 2 underwent a successful percutaneous mitral balloon valvuloplasty (PBMVP) during pregnancy. All pregnancies ended with a liveborn neonate and with no maternal mortality. Peak and mean mitral pressure gradients increased during pregnancy from 13.3 ± 5.3 to 18.6 ± 5.1 mmHg and from 5.9 ± 2.3 to 9.6 ± 3.4 mmHg respectively (P < 0.05). Eight pregnancies (25.8%) were complicated by pulmonary congestion, 2/15 (13.3%) with mild MS, 2/9 (22.2%) with moderate, and 4/7 (57.1%) with severe MS. The adverse event rate was higher among patients with severe MS compared with moderate and mild MS [hazard ratio (HR) 3.15, 95% confidence interval (95%CA) 1.04–9.52 and HR 4.06, 95%CI 1.4–11.19 respectively, P < 0.05]. Nine of 31 deliveries were vaginal; 6 of 22 cesarean sections (27.3%) were performed for cardiac indications.

Conclusions: The number of total adverse events were higher among patients with severe MS. Patients with moderate and mild MS should be treated attentively, but good obstetric and maternal outcome can be expected.

Background: Frequent chronic obstructive pulmonary disease (COPD) exacerbators are at a higher risk of adverse health outcomes when compared to infrequent exacerbators. A COPD frequent exacerbator phenotype and its definition has been reported. Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease. The Hp 2-2 phenotype has been found to have bacteriostatic properties, while the Hp 1-1 phenotype was found to be associated with infections.

Objectives: To determine the correlation in haptoglobin phenotypes and the frequent exacerbator status compared to COPD non-exacerbators.

Methods: Inclusion criteria included previous diagnosis of COPD and presence of at least two documented exacerbations of COPD in the previous 12 months (frequent exacerbator group) or absence of such exacerbations in the previous 24 months (non-exacerbator group). Descriptive data was analyzed using Fisher's exact test and the nonparametric Kruskal–Wallis test. Multivariate logistic regression analysis was performed.

Results: The multivariate logistic regression yielded a model in which haptoglobin phenotype did not have a statistically significant association with frequent exacerbator status. Smoking status was found to be negatively related with the frequent exacerbator status (odds ratio [OR] 0.240, 95% confidence interval (95%CI) 0.068–0.843, P = 0.03). Number of pack-years was negatively related to being a frequent exacerbator (OR 0.979, 95%CI 0.962–0.996, P = 0.02).

Conclusions: We found no relationship between haptoglobin polymorphism and frequent exacerbator status. However, frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years and a negative correlation with current smoking status.

Background: Erythema nodosum (EN) is the most common type of panniculitis, commonly secondary to infectious diseases.

Objectives: To elucidate the causative factors and the clinical presentation of patients with EN (2004–2014) and to compare their data to those reported in a previous study.

Methods: A retrospective study was conducted of all patients diagnosed with EN who were hospitalized at Soroka University Medical Center (2004–2014). The clinical, demographic, and laboratory characteristics of the patients were compared to those in a cohort of patients diagnosed with EN from 1973–1982.

Results: The study comprised 45 patients with a diagnosis of EN. The most common symptoms of patients hospitalized with EN were arthritis or arthralgia (27% of patients). Patients with EN, compared to those reported in 1987, has significantly lower rates of fever (18% vs. 62% P < 0.001), streptococcal infection (16% vs. 44%, P = 0.003), and joint involvement (27% vs. 66%, P < 0.001). In addition, fewer patients had idiopathic causes of EN (9% vs. 32%, P = 0.006).

Conclusions: In the past decades, clinical, epidemiological, and etiological changes have occurred in EN patients. The lowering in rate of fever, streptococcal infection, and joint involvement in patients with EN are probably explained by improvements in socioeconomic conditions. The significantly decreasing rate of idiopathic causes of EN is possibly due to the greater diagnostic accuracy of modern medicine. The results of the present study demonstrate the impact of improvements in socioeconomic conditions and access to healthcare on disease presentation.

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.

Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.

Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.

Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.

Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

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.