Israel Medical Association Journal

Background: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable.

Objectives: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005.

Methods: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007.

Results: The INCR’s completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005.

Conclusions: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Background: Although indwelling catheters are increasingly used in modern medicine, they can be a source of microbial contamination and hard-to-treat biofilms, which jeopardize patient lives. At times 70% ethanol is used as a catheter-lock solution due to its bactericidal properties. However, high concentrations of ethanol can result in adverse effects and in malfunction of the catheters.

Objective: To determine whether low concentrations of ethanol can prevent and treat biofilms of Pseudomonas aeruginosa.

Methods: Ethanol was tested at a concentration range of 0.625–80% against laboratory and clinical isolates of P. aeruginosa for various time periods (2–48 hours). The following parameters were evaluated following ethanol exposure: prevention of biofilm formation, reduction of biofilm metabolic activity, and inhibition of biofilm regrowth.

Results: Exposing P. aeruginosa to twofold ethanol gradients demonstrated a significant biofilm inhibition at concentrations as low as 2.5%. Treating pre-formed biofilms of P. aeruginosa with 20% ethanol for 4 hours caused a sharp decay in the metabolic activity of both the laboratory and clinical P. aeruginosa isolates. In addition, treating mature biofilms with 20% ethanol prevented the regrowth of bacteria encased within it.

Conclusions: Low ethanol concentrations (2.5%) can prevent in vitro biofilm formation of P. aeruginosa. Treatment of previously formed biofilms can be achieved using 20% ethanol, thereby keeping the catheters intact and avoiding complications that can result from high ethanol concentrations.

Background: Cannabinoid hyperemesis syndrome (CHS) is under-recognized by clinicians. It is characterized by nausea, severe abdominal pain, and cyclical vomiting in the context of chronic cannabis use. Oral benzodiazepine is a proposed treatment for CHS. It decreases activation of Cannabinoid Type 1 Receptor (CB1) in the frontal cortex, has a sedative and hypnotic effect and reduces the anticipation of nausea and vomiting. These effects on the central nervous system (CNS) might explain its beneficial antiemetic effect for this syndrome.

Objectives: To increase the index of suspicion for CHS, a unique syndrome that requires a unique treatment with benzodiazepines and not antiemetics.

Methods: We describe a series of four patients with documented cannabis use, who were admitted to an internal medicine department of Meir Medical Center due to symptoms consistent with abdominal pain, nausea, and vomiting. They were initially treated with conventional antiemetics and proton pump inhibitors without response. Intensive investigations were conducted to exclude common and sometimes urgent gastrointestinal or CNS syndromes.

Results: After excluding urgent gastrointestinal and CNS origins for the vomiting, we suspected CHS. All four patients experienced similar symptoms and failure of conventional treatment with antiemetics and proton pump inhibitors. They experienced relief after administration of benzodiazepines.

Conclusions: A high index of suspicion for CHS allows for rapid, appropriate treatment with benzodiazepines, which in turn may lead to cessation of the debilitating symptoms caused by this syndrome.

The use of ultrasound endovaginal probes is common practice in the fields of gynecology and obstetrics. The vagina serves as a host environment for many microorganisms, contributing greatly to its defensive mechanisms. It is not known whether the introduction of other microorganisms into the vaginal region are detrimental or require intensive preventative measures. Several national ultrasonography societies, as well as the Israel Ministry of Health, have addressed the proper and adequate handling of sonographic endovaginal probes, including the use of high-level disinfecting agents following cleansing and prior to using probe covers between patients. However, many obstetrics and gynecology ultrasound units in Israel find it difficult to adhere to these strict disinfecting requirements. While most of the guidelines are based on the theoretical risk of contaminations when ultrasound endovaginal probes are used, the rate of nosocomial infections linked to the use of these probes has yet to be verified. Based on the information available, there is an urgent need to find a solution that enables gynecological ultrasound users to properly disinfect endovaginal probes between patients. Currently, it is almost impossible to pragmatically adhere to the Israel Ministry of Health guidelines. 

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment.

Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions.

Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied.

Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity.

Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.