Israel Medical Association Journal

Illicit drug abuse is a widespread medical problem with numerous sequelae. One of the major challenges in reaching a diagnosis is the difficulty in obtaining accurate details during the medical interview. We describe a patient who initially denied drug abuse while presenting a bizarre nasopharyngeal disease secondary to inhalation of oxycodone-acetaminophen powder.

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Background: Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases.

Objectives: To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts.

Methods: We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities.

Results: The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings.

Conclusions: To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.

Uveal melanoma (UM) affects approximately six individuals per million per year in the United States, with similar rates in Mediterranean countries. Although it appears to have a low prevalence, it is the most common primary intraocular malignancy in adults. Clinically, it presents in most patients as a painless loss or distortion of vision, although it may also be accidentally discovered at routine ophthalmic examination. Associated risk factors include fair skin tone, light eye color, presence of a choroidal nevus, oculodermal melanocytosis (nevus of ota), dysplastic nevus syndrome, and germline BRCA-associated protein 1 mutations (BAP1 mutations) [1].

Background: During combined phacovitrectomy, it is common practice to suture the main corneal incision to prevent intraoperative and postoperative wound leak. However, it may be possible to avoid suturing using a self-sealing corneal incision technique as in standard cataract surgery.

Objectives: To evaluate the clinical outcome, safety, and complications of combined phacovitrectomy without preventive suturing.

Methods: This retrospective case series study included consecutive patients who underwent combined phacovitrectomy between January 2018 and June 2019 for mixed indications. Surgeries were performed at a tertiary university hospital. All surgeries were performed by the same two retinal surgeons. Cataract surgery was performed first, followed by insertion of trocars and vitrectomy. Corneal sutures were not planned but were used at the discretion of the surgeon.

Results: The cohort included 106 eyes of 102 patients. Suturing of the main corneal incision was deemed necessary in five cases (5%) because of a main incision leak or anterior chamber shallowing during trocar insertion. No other complications related to the absence of prophylactic corneal sutures were encountered during surgery or follow-up.

Conclusions: Preventive corneal suturing may not be necessary in combined phacovitrectomy surgery and can be used in the few cases in which it is indicated during surgery.

Background: Nasal obstruction is one of the most common complaints in the practice of rhinology.

Objective: To adapt the Nasal Obstruction Scale Evaluation (NOSE) questionnaire to Hebrew (H-NOSE) and to assess its sensitivity and specificity.

Methods: Candidates for surgical intervention due to isolated nasal obstruction and healthy volunteers (controls) were included in the validation. The English NOSE questionnaire was translated into Hebrew and re-translated for translation validity. Patients completed the H-NOSE questionnaire before and after surgery for nasal obstruction. The same questionnaire was completed by the controls. Test–retest reliability was performed within 2 weeks. Psychometric properties (reliability, reproducibility, validity, and responsiveness) were assessed by a test–retest procedure, internal consistency, correlation to the Hebrew Sino-Nasal Outcome Tool 22 (He-SNOT-22), and response sensitivity.

Results: In total, 179 patients with nasal obstruction and 74 controls completed the questionnaire. Cronbach's alpha score was 0.93 for internal consistency. The receiver operating characteristic curve demonstrated high sensitivity and specificity (< 90%) and area under the curve was 0.97. We found no significant difference in test–retest reliability. The difference between the pre- and postoperative questionnaire scores was highly significant (13.9 ± 4.0 vs. 3.2 ± 4.1, respectively, P < 0.001).

Conclusions: The H-NOSE questionnaire demonstrated reliable internal consistency, sensitivity, specificity, and reliability. The Hebrew version differentiated between patients and heathy controls and was easy to administer. This instrument is useful for Hebrew speaking patients who undergo surgery for nasal obstruction.

Background: Infants younger than 6 months of age are not eligible for coronavirus disease 2019 (COVID-19) vaccinations. Maternal variables during pregnancy and the postnatal period may affect the clinical and laboratory course of COVID-19 positive infants.

Objective: To assess the clinical manifestation and laboratory differences in infants with three maternal variables: breastfeeding, vaccinated, and co-illness.

Methods: We conducted a single-center retrospective cohort study of positive COVID-19 infants with three subgroups of maternal variables. The population included infants under 6 months of age hospitalized due to COVID-19. Data about clinical features, laboratory tests, and maternal information including vaccination status, breastfeeding status and maternal positive COVID-19 infection was gathered. All variables were compared among the three subgroups.

Results: Breastfed infants had shorter hospitalization period (mean 2.61 ± 1.378 days) compared to non-breastfed infants (mean 3.8 ± 1.549) (P = 0.051). COVID-19 infants of positive COVID-19 mothers had a higher absolute neutrophil count (mean 4.4 ± 3.8) compared to infants of COVID-19 negative mothers (mean 2.7 ± 2.4) (P = 0.042).

Conclusion: Breastfeeding was associated with shorter periods of hospitalization in COVID-19 positive infants. In addition, positive COVID-19 infants of mothers who were positive for COVID-19 are likely to have a higher absolute neutrophils count.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

Background: In developed countries, amblyopia has an estimated prevalence rate of 1–4%, depending on the socioeconomic gradient. Previous studies performed on pediatric populations in Ethiopia demonstrated amblyopia rates up to 16.7.

Objectives: To assess rates of amblyopia, refractive errors, strabismus, and other eye pathologies among Ethiopian-born children and adolescents who immigrated to Israel compared to Israeli-born children.

Methods This observational cross-sectional study included children and adolescents 5–19 years of age who immigrated to Israel up to 2 years before data collection and lived in an immigration center. Demographic data and general health status of the children were obtained from the parents, and a comprehensive ophthalmologic examination was performed. Results were compared to Israeli-born children.

Results: The study included 223 children and adolescents: 87 Ethiopian-born and 136 Israeli-born. The rate of amblyopia in the Ethiopian-born group vs. Israeli-born was 3.4% and 4.4%, respectively. Even after controlling for age, there was still no significant difference between the two groups (P > 0.99).

Conclusions: Despite originating from a country with limited resources and fewer medical facilities, the amblyopia rate in Jewish Ethiopian immigrants was not higher, and even mildly lower, compared to Israeli-born children.

Background: Physiotherapy can help treat of trigger fingers (TF).

Objectives: To compare efficacy of fascial manipulation (FM) and traditional physiotherapy (TP) techniques in treatment of TF.

Methods: Nineteen patients were randomized in the FM group and 15 in the TP group. All patients underwent eight physiotherapy sessions. The Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and visual analogue scale (VAS) scores, staging of stenosing tenosynovitis (SST) classification, triggering frequency, grip and pinch strength were recorded before and after treatment. We surveyed participants at 6 months for recurrence, further treatment, and the VAS and QuickDASH scores. The primary outcome measure was reduction in QuickDASH and VAS scores.

Results: Both FM and TF improved the QuickDASH and VAS scores at 6 months follow-up, without a significant difference. The QuickDASH score in the FM group improved from 28.4 ± 17.1 to 12.7 ± 16.3; TF scores improved from 27 ± 16.7 to 18.8 ± 29.4 (P = 0.001). The VAS score improved from 5.7 ± 2.1 to 1.2 ± 2.1 and from 4.8 ± 1.8 to 2 ± 2.6 for both groups, respectively (P < 0.001). SST and grip strength also improved following treatment, regardless of modality. At 6 months, four patients (22%) with an SST score of 1, three (30%) with a score of 2, and two (40%) with a score of 3A underwent additional treatment.

Conclusions: Both FM and TP techniques are effective for the treatment of TF and should be considered for patients who present with SST scores of 1 or 2.

Background: Implant-based breast reconstruction (IBR) is the most common method of reconstruction for breast cancer. Bacterial infection is a well-known risk with reported rates ranging from 1% to 43%. The most common pathogens of breast implant infection described in the literature are Staphylococcus aureus, Staphylococcus epidermidis, and coagulase-negative staphylococci. However, the prevalence of other pathogens and their antibiotic sensitivity profile differs profoundly in different parts of the world.

Objectives: To review the current literature and protocols with respect to our region and to determine a more accurate antibiotic protocol aimed at our specific local pathogens.

Methods: A retrospective review was conducted of all cases of clinically infected implant-based breast reconstruction in our institution from June 2013 to June 2019, as well as review of microbiologic data from around the world based on current literature.

Results: A total of 28 patients representing 28 clinically infected implant-based breast reconstruction were identified during the studied period. Thirteen patients (46.4%) had a positive bacterial culture growth, with P. aeruginosa being the most common microorganism identified (46.1%). Review of international microbiological data demonstrated significant variation at different places and time periods.

Conclusions: Microbiological data in cases of infected breast reconstructions should be collected and analyzed in every medical center and updated every few years due to the variations observed. These data will help to adjust the optimal empirical antibiotic regimens given to patients presenting with infections after breast reconstruction.

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: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia.

Objectives: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not.

Methods: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population.

Results: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia.

Conclusions: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: Hospitalization is an inherently serious event in the oldest-old, as the risk of complications associated with it increases exponentially with age and can lead to death. Despite the size of the problem, few studies have been dedicated to determining mortality predictors among hospitalized older patients, particularly among the oldest-old.

Objectives: To examine in-hospital mortality predictors in the oldest-old adults hospitalized in an acute geriatric ward.

Methods: We retrospectively surveyed electronic hospital health records of 977 elderly patients, aged ³ 90 years, admitted between January 2007 and December 2010 from the emergency department to the acute geriatrics department. We compared the characteristics of the patients who survived to those who died during the hospital stay.

Results: The patients mean age was 93.4 years. In-hospital mortality rate was about 11.6%. Mortality predictors were female sex, on-admission pneumonia, co-morbid congestive heart failure and cerebrovascular accident, high troponin I levels, lower levels of albumin, and higher level of urea (P = 0.032, P < 0.0001, P = 0.0015, P = 0.0049, P = 0.0503, P < 0.0001 and P < 0.0001, respectively). Consumption of ³ 5 drugs and the number of hospitalizations in the last year were inversely associated with death (P = 0.0145 and P < 0.0001, respectively).

Conclusions: Careful evaluation of mortality predictors might be useful for therapeutic planning and identification of potential inpatients for specific interventions. Awareness of in-hospital mortality predictors might contribute to reducing in-hospital death.