Israel Medical Association Journal

Background: Biallelic BLM gene mutation carriers are at an increased risk for cancer, including colorectal cancer (CRC). Whether heterozygous BLM gene mutations confer an increased cancer risk remains controversial.

Objectives: To evaluate CRC and endometrial cancer risk in BLM heterozygous mutation carriers.

Methods: Jewish Ashkenazim at high risk for colon or endometrial cancer and endometrial cancer cases unselected for family history were genotyped for the BLM^Ash predominant mutation.

Results: Overall, 243 high-risk individuals were included: 97 men CRC patients (55.12 ± 12.3 years at diagnosis), 109 women with CRC (56.5 ± 13.7 years), 32 women with endometrial cancer (58.25 ± 13.4 years) and 5 women with both CRC and endometrial cancer. In addition, 120 unselected Ashkenazi women with endometrial cancer (64.2 ± 11.58 years) were genotyped. The BLM^Ash mutation was present in 4/243 (1.65%) high-risk patients; 2 CRC (0.97%) 2 endometrial cancer (5.4%), and 1/120 unselected endometrial cancer patients (0.84%). Notably, in high-risk cases, BLM^Ash mutation carriers were diagnosed at a younger age (for CRC 47.5 ± 7.8 years; P = 0.32 ; endometrial cancer 49.5 ± 7.7 years; P = 0.36) compared with non-carriers.

Conclusions: Ashkenazi high risk CRC/endometrial cancer, and women with endometrial cancer have a higher rate of BLM^Ash heterozygous mutation compared with the general population. BLM^Ash heterozygous mutation carriers are diagnosed with CRC and endometrial cancer at a younger age compared with non-carriers. These observations should be validated and the possible clinical implications assessed.

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.

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Background: In Israel a general code of ethics exists for physicians, drafted by the Israel Medical Association. The question arises whether psychiatrists require a separate set of ethical guidelines.

Objectives: To examine the positions of Israeli psychiatrists with regard to ethics in general and professional ethics in particular, and to explore opinions regarding a code of ethics or ethical guidelines for psychiatry. 

Methods: A specially designed questionnaire was compiled and completed by psychiatrists recruited for the study. 

Results: Most participants reported low levels of perceived knowledge regarding ethics, professional ethics, and the general code of ethics. Older and more experienced professionals reported a higher level of knowledge. Most psychiatrists agreed or strongly agreed with the need for a distinct code of ethics/ethical guidelines for psychiatrists. This support was significantly higher among both psychiatrists under 50 years and residents. 

Conclusions: Our findings suggest that the existing code of ethics and position papers may not be sufficient, indicating a potential need to develop and implement a process to create the ethical code itself. In addition, the findings highlight the importance of ethics education, suggesting that the need for a code of ethics is more urgent in the early stages of professional training, as younger professionals may be more exposed to advanced media technology. While some may fear that a distinct code of ethics will distance psychiatry from modern medicine, others assert that the profession combines aspects from the humanities and social sciences that require a unique sort of management and thus this profession requires a distinct code of ethics.

 

Background: Gastrointestinal malignancies comprise a broad spectrum of neoplasms and have a high overall incidence. The incidence rates in Israel vary among ethnic groups due to different risk factors.

Objectives: To investigate incidence trends of these cancers in Israel in both Jewish and Arab ethnic groups in order to better understand the risks in those groups.

Methods: This study is based on data published by the Israel National Cancer Registry and the Central Bureau of Statistics. We compared statistics between ethnicities and genders. We examined the eight most common gastrointestinal cancers, focusing on colon, rectal and gastric cancers.

Results: Between 1980 and 2012 there was a decline in the incidence of gastric cancer in the Jewish population; in contrast, a significant increase occurred in Arab women, but there was no significant change in Arab men. Colon cancer showed a relative decrease in incidence in the Jewish population, but an increase in the Arab population. A decrease in the incidence of rectal cancer in the Jewish population and an increase in the Arab population was observed. 

Conclusions: Gastric, colon and rectal cancers exhibit differences in incidence and outcome between Jewish and Arab populations in Israel. These differences were not observed in the other five types of less common gastrointestinal cancers.

 

Background: Bioresorbable vascular scaffold (BVS) is a promising technology that potentially offers several advantages over contemporary coronary drug-eluting stents (DES). Crucial to BVS implantation is the correct choice of scaffold size (diameter and length) in order to avoid "geographic miss" in length, provide the maximal support to the vessel wall, and avoid leaving “free-floating” foreign material in the coronary vasculature. 

Objectives: To assess the optimal method for measuring coronary stenosis prior to BVS implantation.

Methods: We compared the performance of two quantitative coronary angiography assessment (QCA) techniques: two dimensional real-time QCA (2D-QCA) and offline 3D QCA (3D-QCA) for the evaluation of coronary lesions in patients enrolled in a multicenter randomized controlled trial of BVS vs. metallic stents, by calculating the weighted kappa value for agreement regarding optimal BVS size with the reference method – CoreLab offline 2D-QCA measurements..In addition, we collected 2 year clinical outcomes (death/myocardial infarction/repeat revascularization/scaffold thrombosis) in BVS-implanted patients.

Results: In 17 patients with available CoreLab data, the weighted kappa for agreement for 3D-QCA was significantly better than for 2D-QCA (0.90, 95%CI 0.72–1.00 vs. 0.439, 95%CI 0.16–0.77). The rate of clinical events at 2 years was low (9.5%).

Conclusions: Initial experience in a small group of carefully selected patients at our institution, suggests that the use of BVS for coronary revascularization is associated with a low rate of adverse events in suitable patients. 3D-QCA may be superior to 2D-QCA analysis in terms of reproducibility, and results in more patients receiving optimal size BVS. 

 

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and new intriguing pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration and organ response.