Israel Medical Association Journal

Background: Burn injuries are an extreme form of traumatic injury and are a global health issue. The Israeli National Burn Unit at the Sheba Medical Center, a tertiary level 1 trauma center and hence the national referral center, treats burn patients admitted both directly and referred from other medical centers. The transfer and handover of patients is a critical step in patient care. In Israel, to date, there is no standardized and accepted transfer request form for burn patients from one medical facility to another.

Objectives: To construct a transfer request form to be used in all future burn patient referrals.

Methods: After reviewing publicly available international transfer forms and comparing them to the admission checklist used at our unit, a structured transfer request form was constructed.

Results: After a pilot study period, testing the form in various scenarios and adapting it, the first standardized transfer form for burn patients in Israel in both English and Hebrew was implemented beginning May 2020.

Conclusions: Implementation of a standardized transfer process will improve communication between healthcare professionals to help maintain a continuum of care. We believe that implementation of a burn transfer form in all future referrals can standardize and assure better care for burn patients, thus improving overall patient care.

Background: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies.     

Objectives: To explore whether obstetric history and parity have a role in the clinician’s decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF).

Methods: In a retrospective study for the period August 2005 to March 2012, data were collected from twin deliveries > 24 weeks, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. 

Results: A total of 1651 twin deliveries > 24 weeks were recorded, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. 

Conclusions: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IVF.  

 

Background: Although fat grafting is a common technique to repair defects after breast cancer reconstruction surgery and has a low complication rate, the relation between fat grafting and the risk of breast cancer is unknown. Clinical trials to investigate this connection can elucidate the benefits and potential risks of fat grafting in oncology patients.

Objectives:To establish an efficient experimental model, using magnetic resonance imaging (MRI) scans, for comparing different breast tumor study groups post-fat grafting. 

Methods: Breast tumor cells were injected into immunocompromised mice. After tumors formed they were removed. Liposuction was performed in a female human donor and fat was collected. Cells were extracted from the fat by enzymatic digestion. Immunocompromised mice were randomized into four groups: a preliminary experiment group and three equal groups according to the type of fat graft: (i) fresh fat enriched with adipose-derived mesenchymal stem cells (AdMSCs), (ii) fresh fat without cell enrichment, and (iii) no fat injected. Tumor volume was assessed by serial MRI scans. 

Results: The rate of tumor growth was higher in the enriched fat group compared to the non-enriched fat group. 

Conclusions: This experimental model is an effective measurable method, allowing future investigation of the effect of autologous fat on breast cancer.

 

Background: Many patients in the internal medicine ward have anemia. The etiology for the anemia may be multifactorial and, in the setting of inflammatory process when the ferritin is increased, it is difficult to diagnose iron deficiency anemia. Soluble transferrin receptor (sTfR) had been suggested as an indicator for iron deficiency. No study has investigated the meaning of high sTfR as the only positive marker of iron deficiency anemia (IDA) caused by gastrointestinal tract (GIT) bleeding in hospitalized patients.

Objectives: To demonstrate the importance of high levels of sTfR as a marker for further GIT investigation in cases of anemia where the level of ferritin was normal or increased

Methods: We retrospectively assessed all patients in an internal medicine ward in our facility with anemia, high sTfR[1] levels (> 5.0 mg/L) and normal or high ferritin levels who underwent esophagogastroduodenoscopy and colonoscopy.

Results: Of 32 patients with anemia and normal or high ferritin levels and high sTfR, 22 patients (68%) had findings that explained IDA[2] (in some patients more than one finding). Those findings were colonic polyps (n=9), carcinoma of colon (n=4), duodenal ulcer (n=4), carcinoma of stomach (n=3), colitis (n=3), atrophic gastritis (n=1), erosive gastritis (n=1) and angiodysplasia (n=1).

Conclusions: High sTfR may be a good indicator of IDA caused by GIT[3] bleeding when the ferritin level is normal or high. GIT investigation is warranted in such cases.

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: The rate in Israel of in vitro fertilization and embryo transfer procedures is the highest among industrialized countries. The procedure has the potential to make treated patients forever happy, should the desired result occur. It also entails, however, numerous potential complications. Patients who are candidates for the procedure should fully understand potential desired and undesired results, and should give their consent based on this understanding. The question whether currently used informed consent forms for these procedures indeed serve this purpose is, however, open.

Objectives: To explore the usefulness of informed consent forms for IVF&ET[1] that are currently used in Israel to represent the potential benefits and risks of the procedures to the patients.

Methods: Informed consent forms for IVF&ET were scrutinized for accuracy, clarity and relevance, by comparison to relevant medical literature. IVF&ET informed consent forms were also assessed whether they fulfill the requirements of the Israeli Law of Patient's Rights.

Results: Currently used "informed" consent forms for IVF&ET were found to be fundamentally inaccurate and outdated. In some cases (number of embryos to be transferred), the information is grossly obscure. In other cases (alternative management) there are glaring omissions.

Conclusions: Informed consent forms for IVF&ET that are currently used in Israel do not adequately serve their stated purpose. Potential risks and benefits are not presented clearly and alternative management strategies are also missing. Thus, they do not fulfill their social, ethical or legal goals. Updating these forms is urgently needed. New versions should clearly distinguish between common (controllable) and uncommon (uncontrollable) complications.

Background: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca⁺⁺ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca⁺⁺ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access

Background: Various medical centers in Israel have recently incorporated electronic medical record systems. Knowing the EMR[1] systems’ features and pattern of use is an essential step for developing locally and nationally integrated systems.

Objectives: To evaluate the status of EMR systems in all major general hospitals in Israel in terms of the applications used and the patterns of use.

Methods: Structured questionnaires were sent to hospital directors and directors of medical informatics units of 26 general and pediatric hospitals serving the vast majority of the population in Israel. The qheuestionnaire included questions pertaining to the EMR systems, their usage and the attitude of the participants to data security issues.

Results: Of the 26 general hospitals 23 (88.4%) returned the questionnaires. Of these, 21 (91.3%) use EMR systems. Twenty-seven different types of systems are in use in Israeli hospitals, and generally more than one type is used in a hospital. [YD1] Physicians work with EMR systems in over 98% of the departments. Also, the EMR systems are used for clinical admission and discharge in over 90% of the departments and for medical daily follow-up in about 45%.

Conclusions: Most of the hospitals in Israel use EMR systems but there is no standard data model. Physicians are the main users but the amount of data entered is still limited. Adoption of standards is essential for integration of electronic patient records across Israeli healthcare organizations.

Background: Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80–100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation.

Objective: To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study.

Methods: A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism- polymerase chain reaction analysis.

Results: Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation £ 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 µg/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation.

Conclusion:We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.