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עמוד בית
Thu, 22.02.24

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July 2014
Michael Arad MD, Tamar Nussbaum MD, Ido Blechman BA, Micha S. Feinberg MD, Nira Koren-Morag PhD,Yael Peled MD and Dov Freimark MD

Background: Contemporary therapies improve prognosis and may restore left ventricular (LV) size and function.

Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM).

Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by ≥ 10% concomitant with ≥ 10% decreased LV end-diastolic dimension.

Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the RR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, lower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose was related to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01).

Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures. 

July 2012
N. Shapira

The Israeli Paradox“ (1996) of low national health rankings despite adequate diet – attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) – coincided with long-observed dichotomies between women’s worse international status vs. men’s advantage. This raised the assumption of a gender link to high n-6 risk as an explanation for both national phenomena. Israeli women’s disadvantage was shown by worse international rankings, i.e., life expectancy (LE), 11th vs. men’s 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010) all-cause and all-cancer mortality both 15th vs. 2nd-best/22 (2000), and 15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Breast cancer mortality rates were +21.8%, vs. prostate -30.4%, compared to Eur-A (27 country) averages (2005). Gender gaps/ratios were smaller than European Union-15, i.e., LE at birth by 34.4–26.4% (2000–2010), respectively, and at 65 years 45.9–35.3% all-cause mortality by 43.3–33.4%, and all-cancer 65.2–58.7%. The Israeli diet was mostly close to guidelines, but n-6 intake (10–12% kcal) was much higher than both recommended and traditional Mediterranean diet“ levels. Research showing females’ greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may suggest their potentially increased production of n-6 eicosanoids with known pro-inflammatory/oxidative/carcinogenic potential. An N-6 Gender Nutrition Paradox“ hypothesis is suggested here, for the first time, associating women’s higher risk and lead in the national paradox“ with greater potential for n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to men. This may also exacerbate women’s risk associated with genetic predisposition (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional diets/foods together with increasing n-6 consumption and western disease rates emphasize the importance of considering gender in nutritional epidemiology and preventive strategies.

April 2012
U. Arad, E. Niv, D. Caspi and O. Elkayam

Monogenic periodic fever syndromes are characterized by recurrent episodes of fever, accompanied by localized inflammatory manifestations. Among them, familial Mediterranean fever (FMF) is the most studied and is by far the most prevalent periodic fever syndrome in Israel. We present a diagnostic workup of a patient suffering from a periodic fever syndrome, initially thought to be FMF and characterized by attacks of fever, severe abdominal pain, a migratory erythematous rash and conjunctivitis. The development of periorbital edema presenting as diplopia led to consideration of tumor necrosis factor receptor-1-associated periodic syndrome (TRAPS). Genetic tests confirmed the diagnosis. This case should alert us that even in Israel, a patient with periodic fever, not fully consistent with the typical features of FMF, should be evaluated for other periodic fever syndromes.

November 2011
A. Blum, C. Simsolo, R. Sirchan and S. Haiek

Background: The "obesity paradox" is defined as an inverse association of good health, survival and obesity. Usually in healthy persons the more obese you are the more metabolic complications you have; however, thin patients with chronic obstructive pulmonary disease (COPD) have more cardiovascular complications and a higher mortality rate.

Objectives: To explore whether atherosclerosis and peripheral artery disease (PAD) contribute to the higher morbidity and mortality of patients with COPD.

Methods: This prospective study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic; all signed a consent form before enrollment. We documented their lung function (FEV1%), body mass index (BMI) and ankle brachial index (ABI). The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD, and between atherosclerosis and severity of lung disease.

Results: Average ABI[1] was 1.01 ± 0.20, BMI[2] was 29.33 ± 7.48 kg/m2, and the abdominal circumference was 107.34 ± 18.87 cm. A positive correlation was found between BMI and ABI (P = 0.001) and between abdominal circumference and ABI (P = 0.000). Patients with peripheral artery disease were older (73.6 ± 11.5 vs. 68.1 ± 11.6 years old, P = 0.04), were thinner (average BMI 25.5 ± 6.2 vs. 31.06 ± 7.3, P = 0.001), and had a lower abdominal circumference (97.7 ± 18.3 vs. 111.7 ± 17.5 cm, P = 0.001). No such difference was observed for years of smoking. Male PAD patients with COPD had a lower BMI (25.2 ± 5.6 vs. 29.9 ± 7.4, P = 0.016), and their abdominal circumference was smaller (96.1 ± 18.0 vs. 110.2 ± 16.5 cm, P = 0.004). Female PAD patients with COPD had a lower BMI (26.3 ± 8.2 vs. 33.1 ± 7.0, P = 0.045), but their abdominal circumference was not different from females without PAD (102.0 ± 19.7 vs. 114.0 ± 19.4 cm, P = 0.162). Patients with PAD had a worse lung disease (FEV1% 34 ± 8% vs. 45 ± 16%, P = 0.01). During the 1 year of follow-up five patients died: two PAD patients due to acute myocardial infarction and three non-PAD patients died from pulmonary insufficiency (two patients) and pulmonary emboli (one patient).

Discussion: We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease. Extensive atherosclerosis in patients with COPD may partly explain the “obesity paradox” observed in patients with COPD.

[1] ABI = ankle brachial index

[2] BMI = body mass index

May 2011
E. Hayim Mizrahi, A. Waitzman, M. Arad and A. Adunsky

Background: Total cholesterol is significantly associated with increased risk of ischemic stroke. Patients with ischemic stroke and high cholesterol levels may show better functional outcome after rehabilitation.

Objectives: To study the possible interrelations between hypercholesterolemia and functional outcome in elderly survivors of ischemic stroke.

Methods: We conducted a retrospective chart review study of consecutive patients (age ≥ 60 years) with acute stroke admitted to a geriatric rehabilitation ward in a university-affiliated hospital. The presence or absence of hypercholesterolemia was based on registry data positive for hypercholesterolemia, defined as total cholesterol ≥ 200 mg/dl (5.17 mmol/L). Functional outcome of patients with hypercholesterolemia (Hchol) and without (NHchol) was assessed by the Functional Independence Measurement scale (FIMTM) at admission and discharge. Data were analyzed by t-test and chi-square test, as well as linear regression analysis.

Results: The complete data for 551 patients (age range 60–96 years)w ere available for final analysis; 26.7% were diagnosed as having hypercholesterolemia. Admission total FIM[1] scores were significantly higher in patients with Hchol[2] (72.1 ± 24.8) compared with NHchol[3] patients (62.2 ± 24.7) (P < 0.001). A similar difference was found at discharge (Hchol 90.8 ± 27.9 vs. NHchol 79.7 ± 29.2, P < 0.001). However, total FIM change upon discharge was similar in both groups (18.7 ± 13.7 vs. 17.6 ± 13.7, P = 0.4). Regression analyses showed that high Mini Mental State Examination scores (β = 0.13, P = 0.01) and younger age (β = -0.12, P = 0.02) were associated with higher total FIM change scores upon discharge. Total cholesterol was not associated with better total FIM change on discharge (β = -0.012, P = 0.82).

Conclusions: Elderly survivors of stroke with Hchol who were admitted for rehabilitation showed higher admission and discharge FIM scores but similar functional FIM gains as compared to NHchol patients. High cholesterol levels may be useful in identifying older individuals with a better rehabilitation potential.

[1] FIM = Functional Independence Measurement

[2] Hcol = hypercholesterolemia

[3] NHchol = non-hypercholesterolemia

March 2011
O. Beyar Katz, A. Ben Barak, G. Abrahami, N. Arad, Y. Burstein, R. Dvir, S. Fischer, J. Kapelushnik, H. Kaplinsky, A. Toren, S. Vilk-Revel, M. Weintraub, I. Yaniv, S. Linn, B. Futerman and M. Weyl Ben-Arush

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

[1] NHL = non-Hodgkin lymphoma

[2] BFM = Berlin-Frankfurt-Munster

November 2010
U. Katzenell, E. Bakshi, I. Ashkenazi, Y. Bar-Dayan, E. Yeheskeli and E. Eviatar

Background: The criteria for tonsillectomy for recurrent tonsillitis were established by prospective studies in the pediatric population and are applied to adults as well. No studies have been conducted to assess whether these guidelines are followed. 

Objectives: To examine the eligibility for tonsillectomy of tonsillectomized patients who were referred because of recurrent acute tonsillitis.

Methods: A retrospective case series in an ambulatory military otolaryngology clinic was conducted, and the medical records of 44 tonsillectomized patients who suffered from throat infections in the year before surgery were analyzed. The number of tonsillar infections that met the referral criteria was counted.

Results: The average number of throat infections that met the referral criteria was 1.89 per year. The average number of visits to the clinic due to upper respiratory tract infection was 12.92 (range 2–36) per year. The average number of visits for any cause was 45.13 (range 6–64) per year. One patient with eight documented throat infections met the criteria of more than six infections in the last year.

Conclusion: Although the referral criteria were not strictly met, we speculate that surgery was probably beneficial. This study shows that the indications for tonsillectomy referral are not strictly followed, and that new criteria for referral of adults for tonsillectomy need to be established.

October 2010
A. Sulkes

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases – such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas – considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is typically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities require prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST[1] refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.


[1] GIST = gastrointestinal stromal tumors

July 2009
D. Freimark, M. Arad, S. Matetzky, I. DeNeen, L. Gershovitz, N. Koren Morag, N. Hochberg, Y. Makmal and M. Shechter

Background: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

[1] CHF = chronic heart failure

June 2008
I. Arad, R. Braunstein and B. Bar-Oz

Background: A substantial number of premature deliveries occur in hospitals lacking neonatal intensive care facilities. We previously demonstrated a comparable outcome of very low birth weight infants delivered in a level II nursery to that of inborn infants delivered in our tertiary care center, but a similar comparison of extremely low birth weight infants has not been done.

Objectives: To compare the neonatal outcome (mortality, severe intraventricular hemorrhage/periventricular leukomalacia, bronchopulmonary dysplasia and intact survival) of inborn and outborn ELBW[1] infants, accounting for sociodemographic, obstetric and perinatal variables.

Methods: We compared 97 ELBW infants (birth weight ≤ 1000 g.) delivered between the years 2000 and 2004 in a hospital providing neonatal intensive care to 53 ELBW babies delivered in a referring hospital. A univariate model was first applied to examine the associations of the individual independent variables with the outcome variable, followed by a logistic stepwise regression analysis for each of the outcome variables. The odds ratios for each predictor were reported as well as their P values and 95% confidence intervals.

Results: In the stepwise logistic regression analysis, accounting for a possible confounding effect of the independent variables, ‘hospital of birth’ remained a statistically significant predictor in the final step only for mortality, with odds ratio (inborns relative to outborns) of 3.32 (95%CI[2] 1.19–9.28, P = 0.022). No statistically significant associations with the other outcome variables were found (severe IVH[3]/PVL[4] odds ratio = 1.99, 95%CI = 0.77–5.14, P = 0.155; BPD[5] odds ratio = 0.60, 95%CI = 0.19–1.91, P = 0.384; intact survival OR[6] = 0.56, 95%CI = 0.23–1.35, P = 0.195).

[1] ELBW = extremely low birth weight

[2] CI = confidence interval

[3] IVH = intraventricular hemorrhage

[4] PVL = periventricular leukomalacia

[5] BPD = bronchopulmonary dysplasia

[6] OR = odds ratio

December 2007
I. Golan, M. Ligumsky and M. Brezis

Background: The frequency of performing percutaneous endoscopic gastrostomy in demented older people has increased in recent years. Several reports indicate flaws in the criteria for performing PEG[1] and in the decision-making process, raising concerns about the adequacy of the consent.

Objectives: To examine knowledge and attitudes of referring doctors and gastroenterologists, and to evaluate attitudes and feelings of family members concerning PEG insertion.

Methods: We conducted a survey of 72 doctors who referred 126 demented patients for PEG, as well as 126 family members and 34 gastroenterologists. Closed-ended questionnaires were designed for each study group, completed by the participants, and computer analyzed.

Results: Approximately 50% of family members expressed dissatisfaction with the decision-making process. Referring physicians reported that PEG insertion was often dictated by the need to transfer patients to a nursing home, with 50% admitting institutional pressure. Most of the referring physicians believed that PEG improved quality of life and longevity, whereas gastroenterologists did not expect an improved quality of life and thought that administrative demands should not intervene in the decision to insert PEG.

Conclusions: The decision-making process in the patient's families regarding PEG insertion for their demented relative is unsatisfactory, often takes place under pressure, and does not provide sufficient information about the procedure or its complications. Interpersonal communication between the patient's family and the medical team need to be improved and institutional demands should not play a major role in the medical decision to insert PEG. Gastroenterologists should take a more active role in the deliberations regarding PEG.

[1] PEG = percutaneous endoscopic gastrostomy

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