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עמוד בית
Thu, 18.07.24

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April 2014
Eyal Bercovich MD, Lital Keinan-Boker MD PhD and Shaul M. Shasha MD
 Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease.

Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.

Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.

Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.

Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

Eyal Kramer MD, Oscar Herman MD, Jacob Frand MD, Lior Leibou MD, Letizia Schreiber MD and Hananya Vaknine MD
 Background: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biologic markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histologic variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

March 2014
Tal Bergman-Levy, Jeremia Heinik and Yuval Melamed
Testamentary capacity refers to an individual's capability to write his or her own will. Psychiatrists are required occasionally to give expert opinions regarding the testamentary capacity of individuals with a medical history or suspected diagnosis of a mental illness. This may stem from the patient/lawyer/family initiative to explore the current capacity to testate in anticipation of a possible challenge, or may be sought when testamentary capacity of a deceased has been challenged. In this article we examine the medico-legal construct of testamentary capacity of the schizophrenic patient, and discuss the various clinical situations specific to schizophrenic patients, highlighting their impact on the medical opinion regarding testamentary capacity through examining the rulings of the Israeli Supreme Court in a specific case where the testamentary capacity of a mentally ill individual who was challenged postmortem, and provide a workable framework for the physician to evaluate the capacity of a schizophrenia patient to write a will.

Sharon Orbach-Zinger, Alexander Ioscovich, Amir Aviram, Sergei Babytz, Shai Fein, Alon Reuveni and Leonid A. Eidelman
 Background: Postoperative pain is a common problem after cesarean deliveries.

Objectives: To characterize common obstetric anesthesia practices after cesarean deliveries in Israel in order to standardize postoperative pain relief protocols.

Methods: A questionnaire was completed during an interview with every obstetric anesthesia unit in all 25 delivery wards in Israel. Data were gathered on intraoperative anesthesia and analgesia protocols as well as postoperative pain relief protocols. A sub-analysis compared units whose director completed a formal obstetric anesthesia training program with those whose directors did not.

Results: Neuraxial morphine was used routinely in 12% of hospitals. No unit providing intrathecal morphine complied with American Society of Anesthesiologists guidelines for respiratory monitoring after use of neuraxial opioids. Additionally, non-steroidal anti-inflammatory drugs (NSAIDs) were used routinely in only half the wards, while patient-controlled analgesia was used infrequently. Postoperative verbal analog scores were not recorded routinely in 71% of units on postoperative day 1. The unit director's training significantly influenced the unit protocols.

Conclusions: Intrathecal morphine, the gold standard of care in cesarean deliveries, is rarely used, mainly due to shortage of staff and lack of formal obstetric anesthesia training. In addition, NSAIDs are also underused. There is a need for more formal training for obstetric anesthesiologists in Israel.

Ilan Goldberg, Oksana Finkel, Andrea GatD, Eli Sprecher and Helena Martinez de Morentin
Erythema nodosum and pyoderma gangrenosum are common skin manifestations in inflammatory bowel diseases. Curiously, these two cutaneous features have seldom been reported to occur simultaneously.  We present three patients affected with inflammatory bowel disease, with concomitant erythema nodosum and pyoderma gangrenosum.

February 2014
Noam Rosen, Roy Gigi, Amir Haim, Moshe Salai and Ofir Chechik
Background: Above-the-knee amputations (AKA) and below-the-knee amputations (BKA) are commonly indicated in patients with ischemia, extensive tissue loss, or infection. AKA were previously reported to have better wound-healing rates but poorer rehabilitation rates than BKA.

Objectives: To compare the outcomes of AKA and BKA and to identify risk factors for poor outcome following leg amputation.

Methods: This retrospective cohort study comprised 188 consecutive patients (mean age 72 years, range 25–103, 71% males) who underwent 198 amputations (91 AKA, 107 BKA, 10 bilateral procedures) between February 2007 and May 2010. Included were male and female adults who underwent amputations for ischemic, infected or gangrenotic foot. Excluded were patients whose surgery was performed for other indications (trauma, tumors). Mortality and reoperations (wound debridement or need for conversion to a higher level of amputation) were evaluated as outcomes. Patient- and surgery-related risk factors were studied in relation to these primary outcomes.

Results: The risk factors for mortality were dementia [hazard ratio (HR) 2.769], non-ambulatory status preoperatively (HR 2.281), heart failure (HR 2.013) and renal failure (HR 1.87). Resistant bacterial infection (HR 3.083) emerged as a risk factor for reoperation. Neither AKA nor BKA was found to be an independent predictor of mortality or reoperation.

Conclusions: Both AKA and BKA are associated with very high mortality rates. Mortality is most probably related to serious comorbidities (renal and heart disease) and to reduced functional status and dementia. Resistant bacterial infections are associated with high rates of reoperation. The risk factors identified can aid surgeons and patients to better anticipate and possibly prevent severe complications.

Itai Gat, Mordechai Dulitzki, Eyal Schiff, Eyal Sivan and Michal J. Simchen
Background: Homozygous carriers of factor V Leiden (FVL) have an up to 80-fold increased risk of venous thrombosis, but the risk of obstetric complications in FVL homozygosity is unclear.

Objectives:
To compare obstetric and thromboembolic complications among factor V Leiden (FVL) homozygous and heterozygous carriers treated with prophylactic dose anticoagulation during pregnancy.

Methods:
In this retrospective case-control study we performed a chart review for the years 2004–2010 of homozygous and heterozygous FVL carriers who were treated with low molecular weight heparin (LMWH) at a dose of 0.6 mg/kg/day during pregnancy. Adverse outcomes included thromboembolic and obstetric complications. A composite adverse obstetric outcome was defined as the presence of at least one of the following: late intrauterine fetal demise, severe intrauterine growth restriction (< 5th percentile), preeclampsia, placental abruption. Pregnancy outcomes of homozygous and heterozygous FVL carriers were compared.

Results:
We compared the pregnancies of 13 homozygous FVL women with those of 82 heterozygous FVL carriers. Thromboembolic events occurred only in heterozygous FVL controls. Gestational age and birth weight were similar. The composite adverse obstetric outcome rate was higher for homozygous compared with heterozygous FVL carriers (23.1% vs. 11%, respectively), although not statistically significant. A trend for prematurity among homozygous FVL patients was evident, with 2/13 women (15.3%) in the homozygous FVL group giving birth before 34 weeks gestation, compared with only 2/82 (2.3%) in the heterozygous group.

Conclusions:
Pregnancy outcome was similar for homozygous and heterozygous FVL carriers on LMWH thromboprophylaxis. The overall likelihood of thromboembolic complications was low. Thromboprophylaxis may decrease the risk for placental and thromboembolic complications in homozygous FVL patients to a similar level as in heterozygotes.
Renata Faermann, Fani Sperber, Schlomo Schneebaum and Daphna Barsuk
Background: The surgical approach to breast cancer has changed dramatically in the past 20 years. The surgical objective today is to remove the tumor, ensuring negative margins and good cosmetic results, and preserving the breast when possible. Magnetic resonance imaging of the breast has become an essential imaging tool prior to surgery, diagnosing additional tumors and assessing tumor extent. Tumor-to-breast volume ratio, an important predictor of breast conservation, can be measured with MRI and may change the surgical decision.

Objectives: To measure the tumor-to-breast volume ratio using MRI in order to assess whether there is a correlation between this ratio and the type of surgery selected (breast-conserving or mastectomy).

Methods: The volumes of the tumor and the breast and the tumor-to-breast volume ratio were retrospectively calculated using preoperative breast MRI in 76 patients who underwent breast-conserving surgery or mastectomy.

Results: Breast-conserving surgery (lumpectomy) was performed in 64 patients and mastectomy in 12. The average tumor-to-breast volume ratio was 0.06 (6%) in the lumpectomy group and 0.30 (30%) in the mastectomy group (P < 0.0001).

Conclusion: The tumor-to-breast volume ratio correlated with the type of surgery. As measured on MRI, this ratio is an accurate means of determining the type of surgery best suited for a given patient. It is recommended that MRI-determined tumor-to-breast volume ratio become part of the surgical planning protocol for patients diagnosed with breast cancer.

January 2014
Limor Aharonson-Daniel, Dagan Schwartz, Tzipi Hornik-Lurie and Pinchas Halpern
Background: Emergency department (ED) attenders reflect the health of the population served by the hospital and the availability of health care services in the community.

Objectives: To examine the quality and accuracy of diagnoses recorded in the ED in order to appraise its potential utility as a guage of the population's medical needs.

Methods: Using the Delphi process, a preliminary list of health indicators generated by an expert focus group was transformed into a query to the Ministry of Health's database. In parallel, medical charts were reviewed in four hospitals to compare the handwritten diagnosis in the medical record with that recorded on the standard diagnosis "pick list" coding sheet. Quantity and quality of coding were assessed using explicit criteria.

Results: During 2010 a total of 17,761 charts were reviewed; diagnoses were not coded in 42%. The accuracy of existing coding was excellent (mismatch 1%–5%). Database query (2,670,300 visits to 28 hospitals in 2009) demonstrated potential benefits of these data as indicators of regional health needs.

Conclusions: The findings suggest that an increase in the provision of community care may reduce ED attendance. Information on ED visits can be used to support health care planning. A "pick list" form with common diagnoses can facilitate quality recording of diagnoses in a busy ED, profiling the population’s health needs in order to optimize care. Better compliance with the directive to code diagnosis is desired.

Johad F. Khoury, Myriam Weyl Ben-Arush, Michael Weintraub, Elisha Waldman, Boris Futerman, Eugene Vlodavsky and Sergey Postovsky
 Background: In osteosarcoma the histological response, measured by the percentage of tumor necrosis, constitutes one of the most significant predictive factors, with better survival in patients whose tumor necrosis is ≥ 90%.

Objectives: To determine if the decrease rate of serum alkaline phosphatase (SAP) levels during the first month of neoadjuvant chemotherapy could serve as a predictive indicator of tumor necrosis and clinical outcome.

Methods: We analyzed the medical files of 53 osteosarcoma patients (19 females, 34 males) (median age 16 years, range 8–24); the disease was metastatic in 12 and localized in the other 41.

Results: The histological responses were good in 38 patients (71.7%) and poor in 15 (28.3%). At a median follow-up of 50 months, 34 patients (64.2%) had no evidence of disease and 19 (35.8%) had died from the disease. High levels of SAP at diagnosis correlated with worse survival (P = 0.002). There was no difference in overall survival between patients whose SAP decrease rate was > 25% and those with a rate < 25% (P = 0.14). Among female patients, "rapid" SAP responders had better survival than "slow" responders (P = 0.026). In patients with metastases the SAP decrease rate was positively correlated with survival (P = 0.042).

Conclusions: There was no evidence that "rapid" SAP responders had a higher percentage of tumor necrosis than "slow" responders, although female "rapid" SAP responders had a better prognosis than "slow" responders. Patients with metastases at presentation and "rapid" SAP response had better prognoses.

Bezalel Podolak, Dorit Blickstein, Aida Inbal, Sigal Eizner, Ruth Rahamimov, Alexander Yussim and Eytan Mor
Joao L. P. Vaz, Mirhelen M. Abreu and Roger A. Levy
 Background: The presence of anti-citrullinated peptide/protein antibody (ACPA) has a high specificity and predictive value for the development of rheumatoid arthritis (RA). Some studies have shown decreased titers of this antibody after treatment with infliximab.

Objectives: To assess the changes in ACPA titers in patients with RA after treatment with infliximab as a first biological agent, and to correlate these variations with non-infusion-related adverse effects.

Methods: In a prospective multicenter observational study involving 48 research centers, we assessed 139 patients with established moderate-to-severe RA diagnosed according to American College of Rheumatology criteria. Samples were collected before and 6–12 months after treatment.

Results: The mean age of the study patients was 50.6 years old, and 118 were female (84.9%). Statistically significant variations in ACPA titers were noted in 47 patients (before and after treatment) (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in 15 (34.7%). No correlation was found between severe or mild adverse effects in patients presenting variations in ACPA titers.

Conclusions: The present study showed that infliximab affected ACPA titers, promoting mainly a decrease; however, this was not related to the occurrence of non-infusion-related adverse effects.

December 2013
Arie Drugan, Irena Ulanovsky, Yechiel Burke, Shraga Blazer and Amir Weissman
 Background: Reduction of fetal number has been offered in high order multiple gestations but is still controversial in triplets. Since recent advances in neonatal and obstetric care have greatly improved outcome, the benefits of multifetal pregnancy reduction (MFPR) may no longer exist in triplet gestations.

Objectives: To evaluate if fetal reduction of triplets to twins improves outcome.

Methods: We analyzed the outcome of 80 triplet gestations cared for at Rambam Health Care Campus in the last decade; 34 families decided to continue the pregnancy as triplets and 46 opted for MFPR to twins.

Results: The mean gestational age at delivery was 32.3 weeks for triplets and 35.6 weeks for twins after MFPR. Severe prematurity (delivery before 32 gestational weeks) was experienced in 37.5% of triplets and in 7% of twins. Consequently, the rate of severe neonatal morbidity (respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage) and of neonatal death was significantly higher in unreduced triplets, as was the length of hospitalization in the neonatal intensive care unit (31.4 vs. 15.7, respectively). Overall, the likelihood of a family with triplets to take home all three neonates was 80%; the likelihood to take home three healthy babies was 71.5%.

Conclusions: MFPR reduces the risk of severe prematurity and the neonatal morbidity of triplets. A secondary benefit is the reduction of cost of care per survivor. Our results indicate that MFPR should be offered in triplet gestations.

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