Israel Medical Association Journal

Background: Diagnosis of onychomycosis is based on potassium hydroxide (KOH), direct smear, culture, and polymerase chain reaction. Nail clippings are rarely used as a diagnostic tool.

Objectives: To evaluate nail clippings for the diagnosis of onychomycosis and to compare it to KOH smears.

Methods: Nail clipping specimens of 39 patients were collected: 34 with onychomycosis proved by positive culture and 5 from normal nails. The specimens were submitted to histological processing and then stained with periodic acid–Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stains. For each nail, KOH smear was also performed. Two pathologists who had no information on the KOH smear and the culture results evaluated the nail clipping histology for the presence of fungal element. Their assessment was compared to the KOH smear and culture results.

Results: Of the 34 specimens that had positive culture, 25 were dermatophytes, 5 were molds, and 4 were candida. Clipping specimens were positive in 30 cases (88%): 23/25 dermatophyte, 4/5 molds, and 3/4 candida. Pathologists were able to classify the pathogens into dermatophytes and non-dermatophytes based on the morphology. PAS stain results were the same as GMS in evaluation of the nail specimen. KOH smear was positive in 29 nails (85%): 20/25 dermatophytes, all 5 molds, and 4 candida. In all five nails where the culture was negative, both clipping and KOH smear did not show fungal elements.

Conclusion: Nail clippings can serve as a rapid, inexpensive, and reliable method for evaluation of onychomycosis, comparable to KOH smear, with the advantage of pathogen group identification.

Background: Omega-3 fatty acids promote fertility in males and females and constitute an important factor in the normal development of the fetus.

Objectives: We investigated the effect of omega-3 supplements during ovulation induction treatment in women with polycystic ovary syndrome (PCOS)-related infertility.

Methods: A randomized, double-blind study was conducted for 60 treatment cycles in 34 women with PCOS-related oligo/anovulation referred to the fertility clinic at the Bikur Cholim/Shaare Zedek Medical Center in Jerusalem, who underwent ovulation induction with clomiphene citrate (50 mg). Seventeen women (mean age 33.9 ± 0.9 years) received omega-3 supplements (3 × 600 mg/day) and 17 received placebo capsules (mean age 32.7 ± 0.9 years) for a maximum of two cycles. We recorded their characteristics and data from their serial hormonal blood tests and ultrasound examinations. We also conducted both univariate and multivariate analyses. The primary endpoint was conception.

Results: There were clinical pregnancies in 8/30 (26.7%) treatment cycles for women receiving omega-3 supplements versus 4/30 (13.3%) cycles with placebo. Among overweight/obese women (body mass index [BMI] 25–35), there were clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 (5.3%) with placebo (P < 0.04). For overweight/obese PCOS women, omega-3, lower BMI rates, and higher values of the endometrium’s thickness increased the odds of becoming pregnant. No harmful side effects from the omega-3 treatment were reported.

Conclusions: Omega-3 supplements demonstrated beneficial effects for fertility in women diagnosed with PCOS. Among the overweight/obese participants, the increased clinical pregnancy rate was significant.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) are new antidiabetic drugs that are recommended by current guidelines as a class I novel glucose-lowering treatment that improves cardiovascular outcome in type 2 diabetes mellitus (T2DM), particularly in patients with cardiovascular disease.

Objectives: To evaluate adherence to the current guidelines for treatment with SGLT2i and GLP1-RA drugs in patients referred to ambulatory consultant cardiology clinics with pre-existing T2DM.

Methods: We studied consecutive new patients with a pre-existing diagnosis of T2DM who were referred to the Clalit Health Services ambulatory consultant cardiology clinic over a 6-month period. The recorded information included demographics, co-morbidities, and prescribed drugs at patient admission.

Results: During the study period, 1782 patients visited our outpatient cardiology clinic. At screening, T2DM was present in 428 patients (24%); 77 (18%) were being treated with SGLT2i, and 39 (9.1%) with GLP1-RA. Patients receiving SGLT2i and GLP1-RA were younger and had more coronary artery disease, lower mean left ventricular ejection fraction, and higher mean estimated glomerular filtration rates than those who were not receiving these drugs. HbA1C was > 7 in 205 (47.9%) patients and > 7.5 in 136 patients (31.8%). Body mass index was > 30 kg/m² in 231 (54%) patients.

Conclusions: GLP1-RA and SGLT2i drugs were found to be administered more frequently than previously reported, but they are not yet satisfactorily prescribed.

Background: Due to the high variability in malignancy rate among cytologically indeterminate thyroid nodules (Bethesda categories III–V), the American Thyroid Association recommends that each center define its own categorical cancer risk.

Objectives: To assess cancer risk in patients with cytologically indeterminate thyroid nodules who were operated at our center.

Methods: In a retrospective study, we analyzed the pathology results of all the patients whose fine needle aspiration results showed Bethesda III–V cytology and who subsequently underwent total thyroidectomy or lobectomy from December 2013 to September 2017.

Results: We analyzed 56 patients with indeterminate cytology on fine needle aspiration. Twenty-nine (52%) were defined as Bethesda III, 19 (34%) Bethesda IV, and 8 (14%) Bethesda V category. Malignancy rates were 38%, 58%, and 100% for Bethesda categories III, IV, and V, respectively. Most malignancies in Bethesda categories III and IV were follicular in origin (follicular thyroid carcinoma and follicular type papillary thyroid carcinoma), while 100% of the patients with Bethesda category V were diagnosed with classical papillary thyroid carcinoma. No correlation was found between sonographic and cytological criteria of nodules with Bethesda categories III and IV and rates of malignancy.

Conclusions: We found higher than expected rates of malignancy in indeterminate cytology. This finding reinforces the guidelines of the American Thyroid Association to establish local malignancy rates for thyroid nodules with indetermined cytology.

Background: Clinical dysentery causes hundreds of thousands of deaths annually worldwide. However, current recommendations reserve antibiotics for those either clinically sick or with highly suspected cases of shigellosis. This treatment stems from rising antibiotic resistance. Children diagnosed with clinical dysentery in the pediatric emergency department (PED) are regarded more cautiously.

Objectives: To explore the use of antibiotics in children diagnosed with clinical dysentery in the PED.

Methods: A retrospective case study of children with clinical dysentery at a single PED during the years 2015 and 2018. Demographics as well as clinical findings were compared to culture results and antibiotic treatment.

Results: The study included 281 children who were diagnosed with clinical dysentery during the study period; 234 (83%) were treated with antibiotics. However, cultures were positive in only 162 cases (58%). Only 32% were Shigella spp. Younger age, fever, and leukocytosis were related to antibiotic treatment.

Conclusions: The diagnosis of clinical dysentery is misgiven commonly in the PED leading to widespread use of antibiotics when not indicated. This treatment may impact antibiotic resistance patterns. Further studies and interventions are necessary to create clear guidelines in the PED setting.

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Background: The prognosis of long-term clinical outcomes for each patient is of utmost importance.

Objectives: To evaluate the association between rates of family attendance during rounds and long-term outcomes.

Methods: We conducted a historic cohort study.

Results: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium.

Conclusions: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

Acute cholecystitis is a common surgical diagnosis. If not addressed properly, it can potentially lead to sepsis, perforation of the gallbladder, and even death.

The most frequent pathogens isolated from bile cultures of patients with cholecystitis are anaerobes and Enterbacterales such as E. coli, Klebsiella species, and Streptococcus species [1].

Streptococcus gordonii belongs to the Viridians streptococci group of oral bacteria and is commonly associated with dental caries. S. gordonii has been previously reported as the causative pathogen in both endocarditis and spondylodiskitis [2]. However, it has rarely been associated with biliary infections. In this report, we presented a patient diagnosed with cholecystitis associated with S. gordonii infection.

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Background: Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.

Objectives: To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.

Methods: We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.

Results: The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.

Conclusions: All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.

Background: Blood pressure (BP) is routinely measured while triaging children presenting to the pediatric emergency department (PED).

Objectives: To determine whether a medical clown shortens the time to acquire a BP measurement among children undergoing triage in the PED.

Methods: The study comprised 133 children. Patients were assigned to one of two groups: with a medical clown or without a medical clown.

Results: The presence of a medical clown led to a significantly shorter time to acquire a blood pressure measurement (60 ± 23 seconds vs. 81 ± 43.5 seconds, P < 0.001. Clowns had a significant effect on shortening total triage length among children of Jewish ethnicity compared to Arab ethnicity (113 ± 353.6 seconds vs. 154 ± 418 seconds, P = 0.012).

Conclusions: Using medical clowns while measuring BP during triage when used in a culturally appropriate manner shortens time.

Background: Vaginal hysterectomy (VH) and colpocleisis are both used for the treatment of advanced pelvic organ prolapse (POP).

Objective: To compare short- and long-term outcomes of vaginal hysterectomy vs. colpocleisis for advanced POP.

Methods: Hospital and outpatient charts of patients who underwent VH or colpocleisis at our institution between January 2006 and December 2015 were reviewed. Clinical data were obtained and analyzed.

Results: In this study, 188 patients underwent VH and 32 patients underwent colpocleisis. The colpocleisis group was significantly older than the VH group (79.5 ± 4.5 vs. 69 ± 6.1 years respectively, P < 0.0001) and presented with significantly higher co-morbidity rates and a higher degree of POP. Perioperative blood loss was significantly lower (250 ± 7.6 ml vs. 300 ± 115 ml, P < 0.0001) and postoperative hospitalization was significantly shorter (2 ± 2.7 vs. 3 ± 2.2 days, P = 0.015) among the colpocleisis group. None of the patients from the colpocleisis group required an indwelling urethral catheter after discharge, compared to 27.5% of the patients from the VH group (P = 0.001). Total postoperative complication rate was significantly lower among the colpocleisis group (25% vs. 31% P < 0.0001). Objective recurrence of POP was significantly more common among the VH group (7% vs. 0% and 21% vs. 0% for the anterior and posterior compartments, respectively, P = 0.04).

Conclusions: Colpocleisis is associated with faster recovery, lower perioperative morbidity, and higher success rates than VH and should be considered for frail and elderly patients.

A 49-year-old woman presented to the emergency department with a 3-day history of altered mental status. The patient’s medical history was unremarkable, and she did not take medications.

Background: The chloride intracellular channel (CLIC) protein family consists of six members in humans. CLICs are unique due to their metamorphic property, displaying both soluble and integral membrane forms. The transmembrane conformation was shown to give rise to ion-channel activity in vitro. In recent years, CLICs were implicated in a growing number of physiological processes in various organ systems and associated with distinct disease states. Indeed, the founding member of the family, CLIC5, was shown to be involved in hereditary deafness and various types of cancer. Nevertheless, the natural interactants and endogenous ligands of CLIC5 have not been discovered yet.

Objectives: To find ligands that affect the biochemical properties and activity of CLIC5. We hypothesized that such ligands could serve as important tools for resolving the long-sought cellular roles of CLICs and may offer novel therapeutic avenues for CLIC-associated conditions.

Methods: Using molecular biology and biochemical methods, CLIC5 was overexpressed in Escherichia coli and purified. Next, a high-throughput differential scanning fluorimetry thermal shift assay (TSA) was established and the interaction of approximately 500 natural compounds was examined.

Results: The TSA-based screening approach developed here allows to evaluate the effect of approximately 100 compounds in parallel within approximately 1 hour. Our proof-of-concept screening yielded 11 potential hits, significantly affecting the thermal stability of CLIC5. By examining the dose-dependence of this effect, we identified a specific interaction of CLIC5 with curcumin.

Conclusions: Using the approach we developed, large libraries of small molecules can be screened efficiently to identify novel CLIC5 interactants. Considering the participation of CLIC5 in various physiological and pathological processes, uncovering ligands that inhibit or activate CLIC5 may provide tools to modulate its activity and possibly to ameliorate CLIC5-related pathologies in the future.

Background: The exposure to ambient particulate matter (PM) is associated with increased morbidity and mortality from respiratory, cardiovascular, and other causes. A major contribution to this adverse effect is attributed to particles at the nanoscale range (ultrafine particles [UFP] particles < 100 nm). Most of the information about human exposure to PM has been collected by environmental monitoring of inhaled particles.

Objectives: To evaluate the use of direct measuring of UFP in the sputum as a biomarker for lung inflammation and functional impairment.

Methods: The study population included 121 patients who underwent an induced sputum (IS) test as a part of a clinical evaluation for respiratory symptoms. Cell differential count was performed, and the UFP content was measured in each IS sample. The UFP content in the sputum was compared among patients with different inflammatory phenotypes based on IS granulocytes levels: eosinophilic inflammation (EI) IS eosinophils > 2.7%, neutrophilic inflammation (NI) IS neutrophils > 65%, and mixed granulocytic inflammation (MGI) including both IS eosinophils > 2.7% and IS neutrophils > 65%. The association between the IS-UFP content and pulmonary function test (PFT) parameters was also tested.

Results: Patients with MGI had a distinct profile of particles in IS, which was characterized by the highest percentage of UFP (relative to larger particles) compared to patients with EI, NI, or normal IS cell count. Furthermore, EI and NI were found to have an interaction effect regarding the IS–UFP profile, as demonstrated by the significantly different IS–UFP profile of patients with MGI compared to the profile associated with EI and NI independently. Last, the profile of UFP in the IS samples was also correlated with patient PFT. Reduced forced mid-expiratory flow (FEF) 25–75 or FEV1 were correlated with a higher IS–UFP mean size. Reduced FEF25–75 was correlated with a lower IS–UFP concentration and percentage relative to larger particles.

Conclusions: To the best of my knowledge, this study is the first to report a distinct IS–UFP profile in patients with MGI, which suggest an interaction effect of EI and NI on the IS–UFP content. This finding may further support the consideration of MGI as a distinct inflammatory phenotype, beyond the simple combination of EI and NI independently. In addition, reduced PFT parameters were associated with a specific change in the IS–UFP profile. The results of this study may shed light on the use of IS–UFP content as a biomarker for lungs inflammation and functional impairment. Further prospective studies are needed to establish a cause and effect relationship between lungs inflammation and functional impairment to the IS–UFP content.