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עמוד בית
Sat, 20.07.24

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July 2014
Aharon Erez MD, Omri Shental MD, Joseph Z. Tchebiner MD, Michal Laufer-Perl MD, Asaf Wasserman MD, Tal Sella MD and Hanan Guzner-Gur MD

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Gideon Nesher MD
Giant cell arteritis (GCA) is considered to be a T cell-dependent disease. Autoantibodies have not consistently been found in GCA. The exception is antiphospholipid antibodies (APLA), which were found in 30–80% of GCA cases. Recently, efforts have been made to seek autoantibodies in GCA using newer methods of detection: serological identification of antigens by recombinant cDNA expression cloning, and a proteomic approach. In these studies, lamin C (a nuclear envelope antigen) was recognized by antibodies in 32% of GCA sera and none of the controls. Other autoantigenic proteins were also identified: lamin A, vinculin (a cytoskeleton antigen), and annexin 5 (an endothelial protein). In a recent study, 92% of 36 patients with GCA and/or polymyalgia rheumatica (PMR) had autoantibodies to a human ferritin peptide (the heavy chain N-terminal); 89% had antibodies to bacterial ferritin peptide of Staphylococcus epidermidis. The significance of these findings needs to be studied further. GCA may be a part of the newly described ASIA syndrome (autoimmune syndrome induced by adjuvants). A recent study from Italy reported 10 cases of GCA/PMR within 3 months of influenza vaccination. These comprised 50% of all cases of GCA/PMR diagnosed during the 6 year period of the study. Another 11 cases of GCA following influenza vaccinations were reported. GCA pathogenesis involves all branches of the immune system, including antigen-presenting cells, T cells and B cells, and autoantibody formation is not uncommon. GCA etiology remains unknown, but may be associated with exposure to bacterial or viral antigens.  
June 2014
Itay Zoarets MD, Natan Poluksht MD and Ariel Halevy MD

Background: Appendectomies are the most common operations performed on an emergency basis. The accepted rate of "white" appendectomies is around 20%. In recent years, computed tomography (CT) scanning has been recognized as a valuable tool with high sensitivity and specificity in the diagnosis of acute appendicitis. The use of CT scans in the management of patients with suspected acute appendicitis is increasing worldwide.

Objectives: To assess whether introducing more liberal use of CT in the management of patients presenting to the emergency room with right lower quadrant pain or suspected acute appendicitis would reduce the rate of “white” appendectomies.

Methods: We conducted a retrospective study of the pathology reports and CT scans of all patients who underwent appendectomy during a 3 year period. We examined the correlation between the rate of CT scans performed and the rate of "white" appendectomies.

Results: Overall, we performed 797 appendectomies during the study period. In 2004, we performed 272 appendectomies and CT in 34 patients (12.5%). In 2005, we performed 275 appendectomies and CT in 83 patients (30.2%). In 2006, we performed 250 appendectomies and CT in 88 patients (35.2%). The percentage of "white" appendectomies decreased from 29% in 2004 to 21.1% in 2005 and to 18.8% in 2006.

Conclusions: It appears that a more selective use of CT scans in the management of suspected appendicitis could reduce the rate of "white" appendectomies.

Dana Livne-Segev, Maya Gottfried, Natalie Maimon, Avivit Peer, Avivit Neumann, Henry Hayat, Svetlana Kovel, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Ben Boursi, Rony Weitzen, Raanan Berger and Daniel Keizman

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

Béatrice Brembilla-Perrot MD, Olivier Huttin MD, Bérivan Azman MD, Jean Marc Sellal MD, Jérôme Schwartz MD, Arnaud Olivier MD, Hugues Blangy MD and Nicolas Sadoul MD.
 Background: Programmed ventricular stimulation (PVS) is a technique for screening patients at risk for ventricular tachycardia (VT) after myocardial infarction (MI), but the results might be difficult to interpret.


Objectives: To investigate the results of PVS after MI, according to date of completion.

Methods: PVS results were interpreted according to the mode of MI management in 801 asymptomatic patients: 301 (group I) during the period 1982–1989, 315 (group II) during 1990–1999, and 185 (group III) during 2000–2010. The periods were chosen based on changes in MI management. Angiotensin-converting enzyme (ACE) inhibitors had been given since 1990; primary angioplasty was performed routinely since 2000. The PVS protocol was the same throughout the whole study period.

Results: Group III was older (61 ± 11 years) than groups I (56 ± 11) and II (58 ± 11) (P < 0.002). Left ventricular ejection fraction (LVEF) was lower in group III (36.5 ± 11%) than in groups I (44 ± 15) and II (41 ± 12) (P < 0.000). Monomorphic VT < 270 beats/min was induced as frequently in group III (28%) as in group II (22.5%) but more frequently than in group I (20%) (P < 0.03). Ventricular fibrillation and flutter (VF) was induced less frequently in group III (14%) than in groups I (28%) (P < 0.0004) and II (30%) (P < 0.0000). Low left ventricular ejection fraction (LVEF) and date of inclusion (before/after 2000) were predictors of VT or VF induction on multivariate analysis.

Conclusions: Induction of non-specific arrhythmias (ventricular flutter and fibrillation) was less frequent than before 2000, despite the indication of PVS in patients with lower LVEF. This decrease could be due to the increased use of systematic primary angioplasty for MI since 2000. 

Haim Shmuely MD, Morad Wattad MD, Alejandro Solodky MD, Jacob Yahav MD, Zmira Samra PhD and Nili Zafrir MD
 Background: The relationship between Helicobacter pylori infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD.


Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

Nasser Sakran MD, David Goitein MD, Asnat Raziel MD, Dan Hershko MD and Amir Szold MD
 Background: Modifications to conventional laparoscopic cholecystectomy (CLC) are aimed at decreasing abdominal wall trauma and improving cosmetic outcome. Although single-incision laparoscopic surgery (SILS) provides excellent cosmetic results, the procedure is technically challenging and expensive compared to the conventional laparoscopic approach.

Objectives: To describe a novel, hybrid technique combining SILS and conventional laparoscopy using minimal abdominal wall incisions.

Methods: Fifty patients diagnosed with symptomatic cholelithiasis were operated using two reusable 5 mm trocars inserted through a single 15 mm umbilical incision and a single 2–3 mm epigastric port. This technique was dubbed “minimal incision laparoscopic cholecystectomy” (MILC).

Results: MILC was completed in 49 patients (98%). In five patients an additional 3 mm trocar was used and in 2 patients the epigastric trocar was switched to a 5 mm trocar. The procedure was converted to CLC in one patient. Mean operative time was 29 minutes (range 18–60) and the average postoperative hospital stay was 22 hours (range 6–50). There were no postoperative complications and the cosmetic results were rated excellent by the patients.

Conclusions: MILC is an intuitive, easy-to-learn and reproducible technique and requires small changes from CLC. As such, MILC may be an attractive alternative, avoiding the cost and complexity drawbacks associated with SILS.

Nadav Michaan MD, Yaron Gil MD, Sagi Amzalag MD, Ido Laskov MD, Joseph Lessing MD and Ariel Many MD

Background: A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent.

Objectives: To compare the perinatal outcome of refugees and Israeli parturients.

Methods: The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls.

Results: During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250).

Conclusions: The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.

Tiberiu R. Shulimzon MD

Interventional pulmonology (IP) is the newest chapter in respiratory medicine. IP includes both diagnostic and therapeutic methods. Nanotechnology, in both instrumental engineering and optical imaging, will further advance this competitive discipline towards cell diagnosis and therapy as part of the future’s personalized medicine.

May 2014
Dorit Blickstein MD, Rima Dardik PhD, Esther Rosenthal MsC, Judith Lahav PhD, Yair Molad MD and Aida Inbal MD
Background: A 75 year old patient presenting with mucocutaneous bleeding was diagnosed with acquired thrombastheniaThe diagnosis was based on lack of platelet aggregation with adenosine diphosphate (ADP), arachidonic acid and collagen, and normal aggregation induced by ristocetin.

Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.

Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.

Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.

Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia. 

Eyal Lotan MD MSc, David Orion MD, Mati Bakon MD, Rafael Kuperstein MD and Gahl Greenberg MD
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