Israel Medical Association Journal

Background: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce.

Objectives: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival.

Methods: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. 

Results: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival.

Conclusions: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.

In this article, we offer a brief summary of the report from the Task Force for the Promotion of the Status of Women in Medicine in Israel. The task force, formed by the Israel Medical Association in 2013, published a comprehensive report in May 2015 dedicated to the promotion of equal opportunities for female doctors in the Israeli healthcare system and in the academic world. The aim of this paper is to present the work of the task force and to highlight its main principles and recommendations against the backdrop of the gender revolution in the Israeli healthcare system and worldwide.

Background: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate.

Objectives: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC.

Methods: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher’s exact tests.

Results: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001).

Conclusions: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.

Medical practice is a form of art, with each complex detail essential to the welfare of the individuals in the care of the physician. Art and medicine have shared a close relationship in a variety of ways for centuries, as demonstrated by anatomical drawings and textbooks from the 16th century. Leonardo da Vinci, driven by his fascination with the details of the human body and how it functioned, succeeded in creating an anatomical model of the cerebral ventricles and the aorta using molten wax and a glass structure, respectively (Heart and Its Blood Vessels). By using water that contained grass seeds, this experiment enabled him to study blood flow. da Vinci’s engrossment with the complexity of the human body is reflected in many of his drawings, including the famous depiction of the human physique in his drawing of the Vitruvian Man. This drawing, which defines the ideal proportions of the human body and their correlation with geometry, is an example of how artistic and scientific objectives integrate with each other.

Background: Medication reconciliation (MR) at hospital admission, transfer, and discharge has been designated as a required hospital practice to reduce adverse drug events.

Objectives: To perform MR among elderly patients admitted to the hospital and to determine factors that influence differences between the various lists of prescribed drugs as well as their actual consumption.

Methods: We studied patients aged 65 years and older who had been admitted to the hospital and were taking at least one prescription drug.

Results: The medication evaluation and recording was performed within 24 hours of admission (94%). The mean number of medications was 7.8 per patients, 86% consumed 5 or more medications. Mismatching between medication prescribed by a primary care physician (PCP) and by real medication use (RMU) was found in 82% of patients. In PCP the most common mismatched medications were cardiovascular drugs (39%) followed by those affecting the alimentary tract, metabolism (24%), and the nervous (12%) system. In RMU, the most commonly mismatched medications were those affecting the alimentary tract and metabolism (36%). Among all causes of mismatched medications, discrepancies in one drug were found in 67%, in two drugs in 21%, and in three drugs in 13%. The mismatching was more common in females (85%) than in males (46%, P = 0.042).

Conclusions: This study provided evidence in a small sample of patients on differences of drug prescription and their use on admission and on discharge from hospital. MR processes have a high potential to identify clinically important discrepancies for all patients.

Background: Invasive cervical cancer is caused by human papillomavirus (HPV).

Objectives: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.

Methods: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006–2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).

Results: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.

Conclusions: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

Background: Israel is a country with a sunny climate; however, vitamin D deficiency and insufficiency are common findings in certain populations whose exposure to sunlight is limited. Medical residency is known for long indoor working hours, thus theoretically limiting the opportunities for sun exposure.

Objectives: To evaluate whether the vitamin D status among residents in a single medical center in Tel Aviv is below the normal range.

Methods: Forty-six residents (28 females, 18 males, average age 33.9 ± 2.8 years) in three residency programs (internal medicine, general surgery/obstetrics and gynecology, pediatrics) were recruited. Demographic data, personal lifestyle, physical activity details and sun exposure duration were obtained by a questionnaire. Serum levels for 25(OH)D were analyzed by a radioimmunoassay.

Results: The mean serum 25(OH)D concentration was 29.8 ± 5.8 ng/ml. According to Institute of Medicine definitions, none of the residents were vitamin D deficient and only two residents (4%) were vitamin D insufficient (15 ng/ml each). The level of 25(OH)D was similar among the various medical specialties. The 25(OH)D levels correlated with the duration of sun exposure and the number of offspring (regression analysis: R2 = 9.2%, P < 0.04 and R2 = 8.9%, P < 0.04, respectively), but not with nutritional data, blood chemistry, or extent of physical activity. 

Conclusions: Most of the residents maintained normal or near normal 25(OH)D levels, indicating that the residency program itself did not pose a significant risk for vitamin D deficiency. 

 

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: Guidelines recommend hepatitis B virus (HBV) vaccination of all adults positive for human immunodeficiency virus (HIV). Immune responses to single-antigen HBV vaccine among HIV-positive patients are low when compared with HIV-negative adults. Sci-B-Vac™ is a recombinant third-generation HBV that may be advantageous in this population.

Objectives: To examine the immune responses to Sci-B-Vac among HIV-positive adults.

Methods: We conducted a prospective cohort study involving HIV-positive adults who had negative HBV serology (HBSAg, HBSAb, HBcoreAb). Sci-B-Vac at 10 µg/dose was administered intramuscularly upon recruitment and after 1 and 6 months. HBSAb levels were checked 1 month after each dose; a level > 10 mlU/ml was considered protective. Data regarding age, gender, CD4 level, and viral load were collected.

Results: The study group comprised 31 patients. Average CD4 count was 503 ± 281 cells/ml, and average viral load was 44 copies/ml. Median interquartile range (IQR) HBVAb titers after the first, second and third immunizations were 0 (0, 3.5), 30 (6, 126) and 253 (81, 408) mlU/ml. Significant titer elevations were found between the second and third immunizations (P = 0.0003). The rate of patients considered protected was 16% after the first, 65% after the second (P < 0.0001), and 84% after the third dose (P = 0.045). No adverse events were reported. More patients under the age of 40 years responded to the first immunization (28% vs. 0%, P = 0.038). CD4 level had no influence on immunization rates.

Conclusions: Sci-B-Vac might achieve better immunization rates among HIV-positive adults compared to the single-antigen vaccine and thus deserves further evaluation in a randomized, double-blind study in this population.

Background: Cannabidiol (CBD)-based treatments for several diseases, including Tourette’s

syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be beneficial and the  scientific clinical background of the drug is continuously evolving. 

Objectives: To investigate the short-term effect of CBD-enriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine. 

Methods: In this anecdotal, retrospective, “compassionate-use”, observational, open-label study, 12 females (age 12–24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2–5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients’ quality of life was evaluated using the medical outcome short-form health survey questionnaire (SF-36).

Results: Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. SF-36 showed significant benefits in the physical component score (P < 0.02), vitality (P < 0.03) and social role functioning (P < 0.02) after the treatment. The administration of hemp oil also significantly reduced body pain according to the SF-36 assessment. No significant differences from the start of treatment to several months post-treatment were detected in role limitations due to emotional reactions (P = 0.02).

Conclusions: This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint. Randomized controlled trials are warranted to characterize the safety profile and efficacy of this compound.