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עמוד בית
Thu, 18.07.24

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February 2021
Nagham Gudban MSc, Itamar Yehuda PhD, William Nasir MD, Soboh Soboh MD, Snait Tamir PhD, and Arnon Blum MD

Background: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM.

Objectives: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation.

Methods: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months.

Results: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group.

Conclusions: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Kfir Siag MD, Salim Mazzawi MD, Ariel Koren MD, Raul Colodner PhD, Muhamed Masalha MD, Roy Biener MD, Nidal Moed MD, Rami Ghanayim MD, and Carina Levin MD PhD

Background: Otogenic cerebral sinus vein thrombosis (CSVT) is a rare but severe complication of otitis media in children. To date, the role of prothrombotic evaluation is still controversial.

Objectives: To report the clinical manifestations, prothrombotic evaluation, and current management of CSVT.

Methods: We performed a retrospective study of nine pediatric patients with otogenic CSVT who underwent prothrombotic evaluation between 2008 and 2018.

Results: Prominent clinical features included persistent otorrhea (88.8%), signs of mastoiditis (88.8%), high fever ≥ 38.3°C (100%), a classic spiking fever pattern (55.5%), and neurological signs (55.5%). A subperiosteal abscess (66.6%) was the most common otitis media complication associated with mastoiditis and CSVT. No microorganism was identified in 55.5% of patients. Cultures collected from ear secretions had a low yield (6.25%). However, PCR assays had a high detection rate (100%; n=3). The prothrombotic evaluation demonstrated an abnormal LAC–dRVVT ratio (6/9), elevated Factor VIII (5/8) (and a combination of both in four patients), antiphospholipid antibodies (2/8), and high homocysteine levels (1/5).The surgical intervention of choice included one-sided mastoidectomy with myringotomy and ventilation-tube placement on the affected side (77.7%). There were no mortalities and no long-term sequela except chronic otitis media (22.2%).

Conclusions: Our findings demonstrate good outcomes for otogenic CSVT treatment with intravenous antibiotics, anticoagulation, and conservative surgical intervention, which supports the current trend in management. The prothrombotic evaluation revealed transient inflammation-related risk factors but did not alter management. Further prospective multicenter studies are needed to determine its relevance

Gassan Moady MD MPH, Shelly Vons MD, and Shaul Atar MD

Background: Takotsubo syndrome (TTS) is a non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete spontaneous recovery. TTS shares several features with acute coronary syndrome (ACS), including clinical presentation, ECG changes, and elevated troponin.

Objectives: To identify different features that may help differentiate between TTS and ACS with presentation based on presenting symptoms and physical examination.

Methods: We compared 35 patients who TTS had been diagnosed with 60 age- and sex- matched patients with ACS (both ST and non-ST segment elevation myocardial infarction) who were hospitalized in Galilee Medical Center through 2011-2015.Basic characteristics and clinical features of the two groups were compared using appropriate statistical tests.

Results: Of the patients with TTS, 21 (60%) reported an emotional trigger (60%) before admission, although they did not have increased prevalence of psychiatric disease compared to ACS patients (5.7% vs. 5%, P = 0.611). There was no difference in the type of chest pain or accompanied symptoms between the groups. Of notice, ECG changes in the TTS group were prominent in the anterior leads, and the patients presented with higher heart rate (86 ± 17 vs. 79 ± 15, P = 0.029) and lower systolic blood pressure (129 ± 26 vs. 142 ± 30, P = 0.034) on admission compared to the ACS group.

Conclusions: There was no reliable feature that could distinguish TTS from ACS based on clinical presentation. TTS should always be in the differential diagnosis in patients with acute chest pain, especially in elderly women

Marwan Hanna Pharm D and Ram Mazkereth MD

Extremely preterm infants are at high risk for mortality and morbidity including neurodevelopmental impairment from invasive Candida infections. Prophylactic antifungal therapy has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants. Prophylactic treatment should be started in the first 48 to 72 hours after birth to extremely low birth weight (ELBW) infants (weighing ≤ 1000 grams at birth) or below 27 weeks gestation age with risk factors, or in any NICU with moderate (5–10%) or high (≥ 10%) rates of invasive candidiasis. Studies demonstrated the benefits of fluconazole prophylaxis regarding its safety of the short-term and long-term without the development of fungal resistance. Empiric antifungal therapy may lower mortality and improve outcomes

Nir Hod MD MHA, Daniel Levin MD, Sophie Lantsberg MD, Gideon Sahar MD, Karen Nalbandyan MD, Aharon Yehonatan Cohen MD, and Aryeh Shalev MD
January 2021
Ariel Tenenbaum MD, Diego Glasbauer MD, and Isaiah D. Wexler MD PhD

The attention of the world is focused on the coronavirus disease-2019 (COVID-19) pandemic. There is s general awareness that certain population groups are at greater risk. However, some other populations may be transparent and may not be receiving the attention they warrant. We focused on those with intellectual disability explaining why they are vulnerable during the current pandemic and require special attention

Mathilda Mandel MD, Michael Gurevich PhD, Michal Mandelboim PhD, Howard Amital MD, and Anat Achiron MD PhD

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

Yasmin Abu-Ghanem MD, Nir Kleinmann MD, Tomer Erlich MD, Harry Z. Winkler MD, and Dorit E. Zilberman MD

Background: Dietary modifications and patient-tailored medical management are significant in controlling renal stone disease. Nevertheless, the literature regarding effectiveness is sparse.

Objectives: To explore the impact of dietary modifications and medical management on 24-hour urinary metabolic profiles (UMP) and renal stone status in recurrent kidney stone formers.

Methods: We reviewed our prospective registry database of patients treated for nephrolithiasis. Data included age, sex, 24-hour UMP, and stone burden before treatment. Under individual treatment, patients were followed at 6–8 month intervals with repeat 24-hour UMP and radiographic images. Nephrolithiasis-related events (e.g., surgery, renal colic) were also recorded. We included patients with established long-term follow-up prior to the initiation of designated treatment, comparing individual nephrolithiasis status before and after treatment initiation.

Results: Inclusion criteria were met by 44 patients. Median age at treatment start was 60.5 (50.2–70.2) years. Male:Female ratio was 3.9:1. Median follow-up was 10 (6–25) years and 5 (3–6) years before and after initiation of medical and dietary treatment, respectively. Metabolic abnormalities detected included: hypocitraturia (95.5%), low urine volume (56.8%), hypercalciuria (45.5%), hyperoxaluria (40.9%), and hyperuricosuria (13.6%). Repeat 24-hour UMP under appropriate diet and medical treatment revealed a progressive increase in citrate levels compared to baseline and significantly decreased calcium levels (P = 0.001 and 0.03, respectively). A significant decrease was observed in stone burden (P = 0.001) and overall nephrolithiasis-related events.

Conclusions: Dietary modifications and medical management significantly aid in correcting urinary metabolic abnormalities. Consequently, reduced nehprolithiasis-related events and better stone burden control is expected.

Eytan Cohen MD, Ili Margalit MD, Tzippy Shochat MSC, Elad Goldberg MD, and Ilan Krause MD

Background: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency.

Objectives: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations.

Methods: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females.

Results: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 μmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66–2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82–2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels.

Conclusions: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Eden Moore, Barbara G. Silverman MD MPH, Yehudit Fishler, Etty Ben-Adiva MPH, Olga Davidov MBA, Rita Dichtiar MPH, Hila Edri, Miriam Zatlawi MPH, and Lital Keinan-Boker MD PhD MPH

Background: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable.

Objectives: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005.

Methods: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007.

Results: The INCR’s completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005.

Conclusions: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

Doron Boltin MBBS, Zaza Beniashvili MD, Adi Lahat MD, Jonathan Hirsch MD, Olga P. Nyssen MD, Francis Mégraud MD, Colm O'Morain MBBS, Javier P. Gisbert MD, and Yaron Niv MD

Background: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines.

Objectives: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel.

Methods: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result.

Results: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment.

Conclusions: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Natav Hendin BSc, Gabriel Levin MD, Abraham Tsur MD, Hadas Ilan MD, Amihai Rottenstreich MD, and Raanan Meyer MD

Background: The sonographic assessment of estimated fetal weight (EFW) is essential for identification of fetuses in weight extremes and aids in peripartum management. However, there are inconsistent reports regarding EFW accuracy.

Objective: To examine maternal and fetal determinants associated with unreliable EFW.

Methods: A retrospective case-control study was conducted at a single, tertiary medical center between 2011 and 2019. All term, singleton deliveries with a sonographic EFW within 2 weeks of delivery were included. Unreliable EFW was defined as > 500 grams discordance between it and the actual birth weight. We allocated the study cohort into two groups: unreliable EFW (cases) and accurate EFW (controls).

Results: Overall, 41,261 deliveries met inclusion criteria. Of these, 1721 (4.17%) had unreliable EFW. The factors positively associated with unreliable EFW included body mass index > 30 kg/m2, weight gain > 20 kg, higher amniotic fluid index, pregestational diabetes, gestational age > 410/7, and birth weight ≥ 4000 grams. On multiple regression analysis, pregestational diabetes (odds ratio [OR] 2.22, 95% confidence interval [95%CI] 1.56–3.17, P < 0.001) and a higher birth weight (OR 1.91, 95%CI 1.79–2.04, P < 0.001) were independently associated with unreliable EFW. On analysis of different weight categories, pregestational diabetes was associated with unreliable EFW only among birth weights ≥ 3500 grams (OR 3.28, 95%CI 1.98–5.44, P< 0.001) and ≥ 4000 grams (OR 4.27, 95%CI 2.31–7.90, P < 0.001).

Conclusion: Pregestational diabetes and increased birth weight are independent risk factors for unreliable EFW and should be considered when planning delivery management.

Yaakov Melcer MD, Shira Dvash MD, Ron Maymon MD, Marina Pekar-Zlotin MD, Zvi Vaknin MD, Tamar Tzur MD, and Noam Smorgick MD

Background: Adnexal torsion in pregnancy is often associated with functional adnexal cysts, especially in pregnancies conceived by ovulation induction (OI) or in-vitro fertilization (IVF). During laparoscopy for adnexal de-torsion, drainage of the functional cysts can be attempted, although this procedure may cause bleeding.

Objectives: To investigate the characteristics of ovarian torsion in pregnancy associated with functional cysts and to compare the rate of torsion recurrence following de-torsion alone versus cyst drainage.

Methods: All cases of surgically diagnosed adnexal torsion occurring during pregnancy between January 2007 and April 2019 in our department were retrospectively analyzed. The cases of torsion associated with presumed functional ovarian cysts were selected. The rate of recurrent torsion during the same pregnancy was compared for de-torsion alone versus de-torsion and cyst aspiration.

Results: Of the 113 women who experienced adnexal torsion during pregnancy, 71 (67.0%) of torsion cases were caused by presumed functional ovarian cysts. Among women with torsion of functional ovarian cysts, the rate of torsion recurrence was significantly higher in patients who underwent de-torsion alone (n=28) compared to women who underwent aspiration and drainage of the ovarian cysts (n=43) (14.3% vs. 0, P = 0.021). There were no cases of intra- or post-operative bleeding in the study cohort.

Conclusions: Functional ovarian cysts are the most common adnexal pathology encountered in pregnant women with torsion. Intra-operative cyst aspiration and drainage may reduce the risk of recurrent torsion. Further multi-center studies are required to validate our data prospectively.

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