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עמוד בית
Tue, 16.04.24

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April 2011
Y. Kilim, N. Magal and M. Shohat

Background: Since the identification of the MEFV gene 198 mutations have been identified, not all of which are pathologic. The screening methods used in Israel to test patients suspected of having FMF include a kit that tests for the five main mutations (M694V, V726A, M680Ic/g, M694I, E148Q), and the sequencing of MEFV exon 10 in combination with restriction analysis for detecting additional mutations.

Objectives: To determine the contribution of testing for five additional mutations – A744S, K695R, M680Ic/t, R761H and P369S – to the molecular diagnosis of patients clinically suspected of having FMF.

Methods: A total of 1637 patients were tested for FMF mutations by sequencing exon 10 and performing restriction analysis for mutations E148Q and P369S.

Results: Nearly half the patients (812, 49.6%) did not have any detectable mutations, 581 (35.5%) had one mutation, 241 (14.7%) had two mutations, of whom 122 were homozygous and 119 compound heterozygous, and 3 had three mutations. Testing for the additional five mutations enabled us to identify 46 patients who would have been missed by the molecular diagnosis kit and 22 patients who would have been found to have only one mutation. Altogether, 4.3% of the patients would not have been diagnosed correctly by using only the kit that tests for the five main mutations.

Conclusions: This study suggests that testing for the additional five mutations as well as the five main mutations in patients with a clinical presentation of FMF adds significantly to the molecular diagnosis of FMF in the Israeli population.

R. Farah and N, Makhoul

Background: Community-acquired pneumonia requiring hospitalization is a severe illness with high mortality, especially if the appropriate treatment is delayed. Sometimes diagnosis is difficult due to an equivocal clinical picture or chest film, or to accompanying diseases that mask or simulate pneumonia.

Objectives: To assess the usefulness of certain inflammatory markers to differentiate pulmonary edema from pneumonia throughout the hospital stay in patients admitted for pneumonia or pulmonary edema of non-infectious origin and to monitor the response to treatment.

Methods: The study group comprised 50 patients admitted for pneumonia, 50 admitted for pulmonary edema and 30 healthy individuals. Blood samples for determination of leukocyte count, erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP), albumin, sCD14 and oxidized fibrinogen were drawn upon admission, at 48 and 72 hours after admission, and at discharge from the intensive care unit.

Results: The levels of sCD14 were similar in both patient groups but higher than control levels during the first 48 hours (P < 0.03). They decreased gradually with hospital stay. The concentration of oxidized fibrinogen was similar in both patient groups and significantly lower than that of the healthy control group throughout the hospitalization period.

Conclusions: Oxidized fibrinogen and sCD14 are not reliable markers for the diagnosis of pneumonia, for its differential diagnosis from pulmonary edema, and for patient follow-up throughout hospitalization. The finding of elevated levels of oxidized fibrinogen in the group of healthy controls warrants further study to identify the factors responsible for altering fibrinogen oxidation. The other markers are more indicative.

February 2011
G. Rubin, S. Krasnyansky, I. Gavish, I. Elmalah, O. Ben-Lulu and N. Rozen

Background: Routine histopathological analysis of bone extracted during total joint replacement is controversial.

Objectives: To evaluate the utility of routine histopathological analysis in total joint replacement.

Methods: We calculated the risk for discrepant diagnosis between the pre- and postoperative histopathological results by performing a meta-analysis of 11 studies (including our data). We also calculated the risk for significant discrepancies.

Results: The discrepant diagnoses analysis showed a random effect of 3% discrepancies (95% confidence interval 1.2–3.7%). Funnel plot indicates a publication bias; consequently, the conclusions from this analysis should be interpreted with caution. Regarding the significant discrepancy in diagnosis, we performed a meta-analysis of nine studies. Fixed-effects analysis of all the studies resulted in 0.16% significant discrepancies (95% CI[1] 0.02–0.30%) with no heterogeneity (Q = 3.93, degrees of freedom = 9, P = 0.14, I2 = 49.2%), and appropriate fixed-effects models.

Conclusions: We recommend no further routine histological examination, reserving this tool for cases with a controversial primary diagnosis and unexpected findings during the operation.

[1] CI = confidence interval

M. Papoulas, N. Lubezky, Y. Goykhman, I. Kori, E. Santo, R. Nakache, J. Klausner and M. Ben-Haim

Background: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar  cholangiocarcinoma  presents a complex surgical challenge.

Objectives: To assess the outcome of the radical approach for the management of types III and IV hilar  cholangiocarcinoma.

Methods: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepatico-jejunostomy.

Results: Fifteen patients (mean age 49 years, range 24–72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (R0) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6–72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively.

Conclusions: In selected patients, the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.

January 2011
J. Farhi and A. Ben-Haroush

Background: Infertility is one of the most prevalent health disorders in young adults.

Objectives: To study the distribution of causes of infertility in couples referred to primary infertility clinics in Israel.

Methods: Data for a 9 year period were derived from two clinics of major women's hospitals run by the country's largest health insurance funds. All patients were treated by one physician. Laparoscopy was not performed to rule out endometriosis.

Results: Of the 2515 couples identified, 1991 (79.2%) had a definitive diagnosis following complete workup (including hysterosalpingography). Mean age was 29.6 ± 6.0 years; mean duration of infertility was 1.7 ± 1.8 years. Primary infertility accounted for 65% of cases. Causes of infertility were male factor (45%), oligo-ovulation disorders (37%), and tubal damage (18%). Infertility factors were identified in the woman alone in 30.6% of cases and the man alone in 29.2%. Two combined infertility factors were found in 18% of patients, and three combined factors in 0.5%. The rate of unexplained infertility (which probably includes non-tubal endometriosis) was 20.7%.

Conclusions: As male factor accounts for almost half of all cases of infertility in couples, sperm analysis is mandatory before any treatment.

September 2010
I. Berger and G. Goldzweig

Background: Most aspects of attention-deficit/hyperactivity disorder diagnosis rely on subjective judgment. Computerized continuous performance tests are designed to improve the validity of the process but are controversial due to low odds ratios. There is a need to find more definitive measures of assessment.

Objectives: To test the validity and reliability of a new tool, a computerized continuous performance functions test, which includes a multi-task approach designed to achieve a higher odds ratio of assessment.

Methods: We applied this test to 58 children aged 6–12 years: 45 were diagnosed as ADHD[1] and 13 non-ADHD children served as a control group.

Results: The CPF[2] test was able to differentiate between non-ADHD and ADHD children. CPF test results were more accurate than other continuous performance tests. The results were statistically significant in all test parameters, confirming the test's validity and reliability. 

Conclusions: The CPF test includes a combination of tasks based on an algorithm designed to test several domains of attention. In this pilot study the CPF test was found to be a valid and reliable tool for the diagnosis of ADHD in children. This test might increase the diagnostic utility of computerized tests. The research points to the need for developing a more definitive process for ADHD diagnosis.


[1] ADHD = attention-deficit/hyperactivity disorder

[2] CPF = continuous performance functions

J. Zlotogora, Z. Haklai, N. Rotem, M. Georgi and L. Rubin

Background: Ultrasound examination of the fetus enables diagnosis of many major malformations during pregnancy, providing the possibility to consider interruption of the pregnancy. As a result, in many cases the incidence of malformations at birth does not represent their true incidence.

Objectives: To determine the impact of prenatal diagnosis and termination of pregnancy on the relative incidence of malformations at birth among Jews and Muslim Arabs in Israel.

Methods: Data on selected major malformations in 2000–2003 were collected from the two large central databases of the Ministry of Health and the Central Bureau of Statistics which contain information regarding births, stillbirths and terminations of pregnancies.

Results: For many malformations the total incidence was much higher than the incidence at birth. For almost all of the malformations studied, the total incidence was higher in Muslims than in Jews and the differences were further accentuated among the liveborn because of the differences in the rate of pregnancy terminations.

Conclusions: In order to detect possible influences of environmental or genetic factors on major malformations in Israel, it is critical to look at data including pregnancy terminations, stillbirths and live births.

June 2010
S.D.H. Malnick, G. Duek, N. Beilinson, V. Neogolani, A. Basevitz, M. Somin, J. Cohen, M. Katz and A. Schattner

Background: In many hospitals a chest X-ray is performed routinely at each patient’s admission. There are scant data regarding its usefulness in contemporary patient populations, which are characterized by patients’ increasing age, severity of illness, and different comorbidities.

Methods: We studied consecutive patients admitted during a 2 month period to a single department of medicine, where hospital policy mandates performing a CXR[1] on admission or soon after. Two senior clinicians who were not involved in the care of these patients assessed the discharge summaries for a clinical indication to perform CXR on admission, as well as its contribution to patient management (major positive, major negative, minor positive, or no contribution). Logistic regression analysis was performed with the SPSS 12 software program.

Results: The study population comprised 675 patients whose mean age was 64.5 ± 17.2 years. Their presenting complaints included chest pain (18%), dyspnea (12%), weakness (10.5%), fever (9%), abdominal pain (8%) and neurologic complaints (7.5%). Physical examination of the chest was normal in 585 (87%) of the cases and abnormal in 87 (13%). Examination of the heart was normal in 518 (77%) and abnormal in 129 (19%). In 19.6% (130 cases) CXR was not performed. Of the 545 CXRs done, 260 (48%) were normal. In only 128 (23.5%) did the admission CXR make a major positive contribution to diagnosis or treatment. In 61 (11.2%) it provided a minor positive contribution and in 153 (28.1%) a major negative contribution. In 184 patients (33.8%) the CXR did not affect either diagnosis or management. It made a major positive contribution to management in patients for whom there was an indication for performing the X-ray (odds ratio 10.3, P < 0.0005) and in those with a relevant finding on physical examination (OR[2] 1.63, P = 0.110). For a major negative contribution of the CXR to management (i.e., ruling out clinically important possibilities), the clinical indication was also very important (OR 72.9, P < 0.005). When patients with either a clinical indication for performing a CXR or an abnormal chest examination were excluded, 329 patients remained (60% of the 545 who had a CXR) in only 12 of them (3.6%) did the routine admission CXR contribute to patient management.

Conclusions: A routine admission CXR has a significant impact on patient management only in those patients in whom there are relevant findings on physical examination or a clear clinical indication for performing the test. There is no need to routinely order CXR on admission to hospital.


[1] CXR = chest X-ray

[2] OR = odds ratio

May 2010
S. Eventov-Friedman, H. Leiba, O. Flidel-Rimon, A. Juster-Reicher and E.S. Shinwell

Background: The American Academy of Pediatrics recently published recommendations for the red reflex assessment in the newborn period to detect and treat ocular disorders as early as possible, and to prevent lifelong visual impairment and even save lives. The test is technically simple to perform, non-invasive, requires minimal equipment and can detect a variety of ocular pathologies including cataracts and retinal abnormalities. No specific national guidelines exist on this issue.

Objectives: To document the implementation of red reflex examination in routine neonatal care and present the findings.

Methods: Our clinical experience following implementation of the red reflex test into the newborn physical examination in a single center was reviewed. In addition, an electronic mail questionnaire was sent to all neonatology departments in Israel regarding the performance of the red reflex test.

Results: During 2007–2008, five infants were identified with congenital cataracts at days 2–6 of life prior to discharge from hospital. Surgery was performed in one infant at age 2 months and all infants underwent a thorough follow-up. The incidence of congenital cataract in our center was 1:2300. Less than half the neonatology departments have endorsed the AAP[1] recommendation and perform the red reflex test routinely.

Conclusions: Abnormal red reflex test after delivery enables a rapid ophthalmologic diagnosis, intervention and close follow-up. We recommend that red reflex screening be performed as part of the newborn physical examination if abnormal, an urgent ophthalmologic referral should be made.

[1] AAP = American Academy of Pediatrics

H. Rosenblum, Y. Bar-Dayan, Z. Dovrish, S. Lew, N. Weisenberg, A. Neumann, T. Klein and H. Amital

Background: Obstruction of urine outflow can result from mechanical blockade as well as from functional defects. In adults, urinary tract obstruction is due mainly to acquired defects, such as pelvic tumors, calculi, and urethral stricture. In childhood it is mostly due to congenital malformations. In this article we present two rare cases of acute obstructive renal failure that presented with hydronephrosis. These cases underline the wide range of causes that may lead to this clinical feature. 

March 2010
O. Kobo, M. Hammoud, N. Makhoul, H. Omary and U. Rosenschein

Background: Renal artery stenosis is one of the most frequent causes of secondary hypertension. Appropriate methods for screening, diagnosis and therapy are currently under debate.

Objectives: To evaluate and recommend methods for screening and diagnosing renal artery stenosis, and to assess the clinical outcomes of renal artery stenting.

Methods: A total of 450 patients undergoing non-emergent coronary angiography fulfilled the selection criteria for selective renal arteriography; those with severe (luminal narrowing ≥ 70%) renal artery stenosis underwent percutaneous transluminal renal angioplasty with renal artery stenting.

Results: Of 166 patients (36.9%) with renal artery stenosis, 41 (9.1%) had severe stenosis that required renal artery stenting, and 83% had ostial renal stenosis. The primary success rate was 100% and there were no complications. During the follow-up period, two patients required a second PTRA[1]. After stent deployment, significant reductions were observed in systolic and diastolic pressures (P < 0.001 and P = 0.01, respectively) and in the number of antihypertensive drugs used by the patients (P < 0.001). These reductions were sustained during follow-up. Hypertension was cured (systolic blood pressure < 130 mmHg) in 9 (21.4%) and improved in 27 (64.3%) patients. Plasma creatinine did not change significantly.

Conclusions: Selective renal angiography is an effective diagnostic tool for identifying symptomatic cases of renal artery stenosis in patients undergoing coronary angiography. Our finding of a high success rate and low complication rate supports the use of primary renal artery stenting in symptomatic patients with renal artery stenosis.

[1] PTRA = percutaneous transluminal renal angioplasty

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