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עמוד בית
Tue, 26.11.24

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June 2014
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.

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. 

Vanya Tsvetkova-Vicheva PhD, Emiliana Konova PhD, Tcvetan Lukanov PhD, Svetla Gecheva MD, Angelika Velkova PhD Dsc and Regina Komsa-Penkova PhD
 Background: Interleukin-17A (IL-17A)-producing CD4+T helper cells have been implicated in allergic inflammation; however, the role of IL-17A in allergic rhinitis (AR) patients with different degrees of atopy and airway reactivity to methacholine (Mch) has not been examined.

Objectives: To explore IL-17A-producing CD3+CD4+T cells in peripheral blood of patients with persistent AR and assess the degree of atopy, eosinophil count (Eo count), and bronchial hyper-responsiveness (BHR) to methacholine.

Methods: The study involved 61 patients and 30 controls. The percentage of CD3+CD4+IL-17A+T cells in peripheral blood was measured by flow cytometry, bronchial challenges with Mch were performed, as was skin prick tests with standard inhalant allergens, and Eo count was measured. Atopic status was determined by the number of positive SPT results and wheal mean diameter.

Results: A statistically significant difference in Th17 cell percentage was found in the AR and control groups (2.59 ± 1.32% and 1.24 ± 0.22% respectively, P = 0.001). Forty-one patients (67.2%) were polysensitized to indoor and outdoor allergens, while 20 (32.8%) had positive skin prick tests to indoor allergens. CD4+T cells were significantly higher in the patient group compared to the control group (2.91 ± 1.5% versus 1.91 ± 0.62%, P = 0.005), as was Eo count (4.48 ± 2.13 vs. 2.32 ± 1.83) (P = 0.0001). Forty-one in the AR group (67%) and 7 (23%) in the control group were Mch-positive (P = 0.001). The percentage of IL-17A-producing CD4+T cells was significantly higher in males compared to females (3.15 ± 1.8% versus 2.31 ± 0.9%, P = 0.02)

Conclusions: Polysensitized AR patients exhibited higher IL-17A-producing CD4+T cell levels and eosinophil counts. Male patients displayed a higher frequency of IL-17A-producing T cells. 

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.

Mahmud Mahamid MD, Omar Abu-Elhija MD, Mosab Samamra MD, Ammad Mahamid MD and William NseirMD

Background: Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely investigated.

Objectives: To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata.

Methods: The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels.

Results: Mean CRP values were significantly higher in the AA group than the control group (1.1 ± 0.7 mg/dl vs. 0.4 ± 0.8 mg/dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 ± 10.18 ng/ml vs. 21.55 ± 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6–4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95%CI 2.2–3.1, P = 0.02) were associated with AA. 

Conclusions: We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be significant risk factor for AA occurrence.

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.

Tal Zilberman MD, Tanya Zahavi MD, Alexandra Osadchy MD, Naomi Nacasch MD and Ze'ev Korzets MBBS
May 2014
Bonaguri Chiara PHD, Orsoni Jelka Gabriella MD, Russo Annalisa PHD, Rubino Pierangela MD, Bacciu Salvatore MD, Lippi Giuseppe MD Melegari Alessandra PHD, Zavota Laura MD, Ghirardini Stella AO and Mora Paolo MD

Background: Cogan’s syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a “typical” form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an “atypical” form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL).

Objectives: To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups.

Methods: We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70.

Results: Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups.

Conclusions: Anti-Hsp70 antibodies can be considered a serological marker of “typical” CS. “Atypical” CS is conceivably a sort of “melting pot” of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

Yael Zenziper BPharm, Daniel Kurnik MD, Noa Markovits MD, Amitai Ziv MD MHA, Ari Shamiss MD MPA, Hillel Halkin MD and Ronen Loebstein MD

Background: Prescription errors are common in hospitalized patients and result in significant morbidity, mortality and costs. Electronic prescriptions with computerized physician order entry systems (CPOE) and integrated computerized decision support systems (CDSS providing online alerts) reduce prescription errors by approximately 50%. However, the introduction of CDSS is often met by opposition due to the flood of alerts, and most prescribers eventually ignore even crucial alerts (“alert fatigue”). 

Objectives: To describe the implementation and customization of a commercial CDSS (SafeRx®) for electronic prescribing in Internal Medicine departments at a tertiary care center, with the purpose of improving comprehensibility and substantially reducing the number of alerts to minimize alert fatigue. 

Methods: A multidisciplinary expert committee was authorized by the hospital administration to customize the CDSS according to the needs of six internal medicine departments at Sheba Medical Center. We assessed volume of prescriptions and alert types during the period February–August 2012 using the statistical functions provided by the CDSS. 

Results: A mean of 339 ± 13 patients per month per department received 11.2 ± 0.5 prescriptions per patient, 30.1% of which triggered one or more CDSS alerts, most commonly drug-drug interactions (43.2%) and dosing alerts (38.3%). The review committee silenced or modified 3981 alerts, enhancing comprehensibility, and providing dosing instructions adjusted to the patient’s renal function and recommendations for follow-up. 

Conclusions: The large volume of drug prescriptions in internal medicine departments is associated with a significant rate of potential prescription errors. To ensure its effectiveness and minimize alert fatigue, continuous customization of the CDSS to the specific needs of particular departments is required.

 

Lidia V. Gabis MD and John Pomeroy MD
Background:  Autism spectrum disorders (ASD) represent a common phenotype related to multiple etiologies, such to genetic, brain injury (e.g., prematurity), environmental (e.g., viral, toxic), multiple or unknown causes. 

Objectives: To devise a clinical classification of children diagnosed with ASD according to etiologic workup.

Methods: Children diagnosed with ASD (n=436) from two databases were divided into groups of symptomatic, cryptogenic or idiopathic, and variables within each database and diagnostic category were compared.

Results: By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. Conclusions: Differences in gender and clinical and diagnostic features were found when etiology was used to create subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s).

Donato Rigante MD PhD, Aurora Rossodivita MD PhD and Luca Cantarini MD PhD
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