Israel Medical Association Journal

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Age-related changes in multiparametric magnetic resonance imaging (mpMRI) of the prostate have been reported in the general population but not in screening cohorts.

Objectives: To evaluate age-related changes on prostatic mpMRI in a screening cohort of BRCA1/2 mutation carriers.

Methods: Asymptomatic BRCA1/2 mutation carriers underwent mpMRI as part of a screening program. All included patients were followed for 3 years with no evidence of prostate cancer. mpMRIs were retrospectively evaluated by two abdominal radiologists for peripheral zone (PZ) patterns on T2 (homogenous hyperintensity, wedge-shaped hypointensities, patchy hypointensities, or diffuse hypointensity), and transition zone (TZ) pattern on T2 (homogenous, heterogeneous, nodular). Apparent diffusion coefficient (ADC) values of PZ and TZ were measured. Statistical analysis was performed using a predefined age cutoff of 50 years old.

Results: Overall, 92 patients were included: 38 in the younger age group (40–49 years) and 54 in the older age group (50–69 years). PZ homogenous hyperintensity and wedge-shaped hypointensities were more common in the older patients, whereas diffuse hypointensity was more common in younger patients (P < 0.001 for both readers) with substantial inter-reader agreement between the readers (kappa=0.643). ADC values were lower in young patients in the PZ (P < 0.001) and TZ (P = 0.003).

Conclusions: Age-related differences in mpMRI were validated in BRCA mutation carriers. As some features overlap with prostatic carcinoma, awareness is crucial, specifically to diffuse T2 hypointensities of the PZ and lower ADC values in the PZ and TZ, which are more common in younger patients.

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.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Background: Advances in examination techniques have improved routine assessment of non-gynecological structures in the pelvis.

Objectives: To describe the sonographic features of incidental urological abnormalities found during gynecological transvaginal ultrasound.

Methods: A retrospective descriptive analysis of patients who underwent gynecological ultrasound and were diagnosed with urologic findings was performed. The sonographic features of the findings including size, echogenicity, and vascularity were examined.

Results: Gynecological ultrasound diagnosed urological findings in nine women. Two had primary neoplasms of the urinary bladder, one had metastases to the urinary bladder, one had polyps in the distal ureters, four presented with calculus in the distal ureters (one of them was 19 weeks pregnant), and one showed diverticulum of the urethra. At presentation five women (56%) had urinary complaints. Two patients (22%) with abdominal pain with distal ureteral calculi had normal transabdominal ultrasound targeted to the urinary system prior to the gynecological sonography.

Conclusions: Transvaginal ultrasound is useful in the diagnosis of urological abnormalities, mainly in the urinary bladder and the distal ureters. We suggest adding transvaginal assessment for female patients with urinary complains in whom transabdominal ultrasound of urinary system was unremarkable.

Background: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality.

Objectives: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations.

Methods: Data were collected from all patients under 18 years who met our internal guidelines from 2015–2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample.

Results: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34).

Conclusions: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

Background: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert.

Objectives: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress.

Methods: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial.

Results: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress.

Conclusions: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems

Background: Fetal ventriculomegaly is one of the more common fetal anomalies detected during prenatal screening.

Objectives: To assess the rate of genetic aberrations as the cause for ventriculomegaly in these fetuses.

Methods: A historic cohort study was conducted on 164 fetuses with sonographic diagnosis of ventriculomegaly. All cases were analyzed for karyotype and 41 cases were further analyzed by chromosomal microarray (CMA). The study group was subdivided by laterality, severity, and whether the ventriculomegaly was an isolated finding or not. Subgroups were compared and the study group was compared to a control group of 209 fetuses.

Results: Karyotype aberrations were more common among fetuses with ventriculomegaly (6.6%) compared to controls (0%, P < 0.001). CMA aberrations were more common in the non-isolated ventriculomegaly cases (24.1%) compared to controls (6.2%, P = 0.031). The rate of genetic aberrations was not associated with the degree of dilatation or laterality.

Conclusions: It is equivocal whether CMA testing should be conducted on every amniotic fluid sample taken from fetuses with isolated ventriculomegaly. However, if more anomalies are detected during an anatomical survey, CMA analysis should be conducted to decrease oversights of genetic diagnoses.

Background: Evaluation of low rectal anastomosis is often recommended prior to ostomy closure, but the efficacy of such evaluations is uncertain.

Objectives: To assess whether routine colonic preoperative evaluation has an effect on postoperative ileostomy closure results.

Methods: We performed a retrospective study evaluating all patients who underwent ileostomy closure over 9 years. Patient demographics, clinical, surgical details, and surgical outcomes were recorded and analyzed.

Results: The study comprised 116 patients who underwent ileostomy closure, of them 65 were male (56%) with a mean age of 61 years (range 20–91). Overall, 98 patients (84.4%) underwent colonic preoperative evaluation prior to ileostomy closure. A contrast enema was performed on 61 patients (62.2%). Abnormal preoperative results were observed in 12 patients (12.2%). The overall complication rate was 35.3% (41 patients). No differences in postoperative outcome was observed in patient gender (P = 1), age (P = 0.96), body mass index (P = 0.24), American Society of Anesthesiologists score (P = 0.21), and the Charlson Comorbidity Index score (P = 0.93). Among patients who had postoperative complications, we did not observe a difference between patients who underwent preoperative evaluation compared to those who did not (P = 0.42). No differences were observed among patients with preoperative findings interpreted as normal or abnormal (P = 1). The time difference between ileostomy creation and closure had no effect on the ileostomy closure outcome (P = 0.34).

Conclusions: Abnormal findings in preoperative colonic evaluation prior to ileostomy closure were not associated with worse postoperative outcome.

Background: With the recent introduction of high-sensitivity troponin (hsTn), the incremental benefit of stress myocardial perfusion imaging (MPI) in the evaluation of patients who present to the emergency department (ED) with acute coronary syndrome (ACS) is unclear.

Objectives: To assess the added value of stress MPI in low-risk ACS patients with normal range hsTnI.

Methods: We analyzed all patients who were hospitalized at our medical center from February 2016 to November 2017, who presented with low-risk ACS and underwent stress MPI, and in whom hsTnI was in the normal range after the introduction of hsTnI.

Results: During the study period, 161 patients were admitted with a diagnosis of unstable angina (i.e., ACS with normal range hsTnI) and underwent stress MPI during index admission. The study population included 52/161 patients (31.7%) with low-risk ACS who had no indication for initial invasive strategy. No patients had positive MPI. One patient underwent coronary angiography due to suggestive history; however, he did not have a significant coronary artery disease and had no indication for percutaneous coronary intervention.

Conclusions: In patients with low-risk ACS and normal range hsTnI without additional high-risk features, stress MPI has little additional value for the correct diagnosis and management. Prospective studies are warranted to confirm whether resting hsTnI could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and thus, improve patient management.

Background: Tumor treating fields (TTFields) are low-intensity, intermediate frequency electric fields that affect proliferating cells. TTFields are FDA approved for treatment of newly diagnosed and recurrent glioblastoma. Combining TTFields with immunotherapy is a rational approach due to their different mechanisms of action (MOA) and to the ability of TTFields to induce immunogenic cell death. Conversely, TTFields may interfere with immune functions critical for effective T-cell responses.

Objectives: To evaluate the effects of TTFields on pivotal antitumoral T-cell functions.

Methods: T-cells from healthy donor peripheral blood (PB) or from viably dissociated human glioblastoma samples were cultured under normal or TTFields conditions, with or without superantigen stimulation. Multiparametric flow cytometry (8-color) was used to assess T-cell responses by monitoring select pivotal functions: proliferation (CFSE), IFNγ secretion, cytotoxic degranulation (CD107a), and activation/exhaustion (PD-1). Cellular viability was assessed in a dedicated assay. A chimeric antigen receptor (CAR) T-cell-based assay directly evaluated cellular cytotoxicity.

Results: Activated PB T-cells and tumor-infiltrating T-cells (TILs) preserved all monitored anti- tumoral functions under TTFields, apart from proliferation. This finding also applied specifically to PD-1 + TILs, comprised predominantly of tumor antigen-specific cells. Activated T-cells that attempted to proliferate under TTFields demonstrated decreased viability, in line with TTField MOA. Small or no reduction in viability was found in T-cells that did not attempt to proliferate, whether activated or resting.

Conclusions: All monitored anti-tumoral T cell functions, except for proliferation, were unhindered by TTFields. Our results support further investigation into combinations of TTFields with T-cell based immunotherapeutic approaches.

Background: Hypertrophy of the adenoids is common in children. However, the anatomical site makes the adenoids difficult to assess, and studies evaluating the subject are ambiguous, especially with regard to the use of X-ray as an evaluation tool.

Objectives: To compare medical history with clinical, radiological, and endoscopic evaluations of the adenoids and compare obstructed and non-obstructed children relative to the assessment methods.

Methods: A prospective comparative study was conducted with children who were suspected of having enlarged adenoids. All parents completed a medical history questionnaire and patients underwent clinical evaluation based on Nasal Obstruction Index (NOI) scores, radiological assessment based on the lateral neck X-ray adenoid–nasopharynx (A/N( ratio, and endoscopic evaluation based on anatomical relations. Spearman correlations were used for comparison between methods.

Results: We evaluated 36 patients, median age 5.33 years. Correlation measurements for clinical assessment and questionnaire (r = 0.582, P < 0.0001), questionnaire and endoscopy (r = 0.462, P = 0.005), and clinical assessment and nasal endoscopy (r = 0.621, P < 0.0001) were statistically significant. None of the parameters correlated with the radiological findings. A statistically significant difference was found between the obstructed and non-obstructed groups in both questionnaire (P = 0.004) and clinical assessment (P < 0.0001). However, no difference was found in X-ray measurements.

Conclusions: Lateral neck X-ray measurements were not correlated to symptoms, signs, or endoscopic findings. Therefore, medical professionals should use lateral neck radiography when considering adenoidectomy only on a highly selective basis.

Background: Frozen section (FS) is often performed when histopathological evaluations are urgently required for implementation of therapeutic measures. In dermatology, this method is most commonly used to evaluate excision margins of tumors. FS are also routinely employed to differentiate toxic epidermal necrolysis from staphylococcal scalded skin syndrome. However, little is currently known about the performance of FS in the diagnosis of inflammatory dermatoses.

Objectives: To compare histopathological diagnoses in a series of patients with a clinical diagnosis of an inflammatory dermatosis for which FS and paraffin-section (PS) specimens were obtained on the same day.

Methods: We conducted a single-center retrospective analysis of 43 cases. All histological slides were reviewed by a single dermato-pathologist. Concordance was calculated between FS and PS.

Results: Patients were divided into three groups according to diagnosis: papulosquamous diseases (group I), drug eruptions (group II), and a heterogeneous group (group III) that included cases of bullous vasculitis and Sweet syndrome. Among the three groups, the results of FS and of PS were discordant only in five cases (5/43, 11.6%). Compared to PS, FS had a sensitivity of 92.9% [95% confidence interval (95%CI) 64.17–99.63%] and a specificity of 100% in group I, sensitivity of 90.9% (95%CI 57.12–99.52%) and specificity of 100% in group II, and sensitivity of 83.33% (95%CI 60.78–94.16%) and specificity of 100% in group III. The degree of agreement between the results of the FS and of the PS was almost perfect (kappa = 0.95, 0.93 and 0.85 respectively).

Conclusions: This study suggests that FS is a valid approach for the rapid diagnosis of inflammatory dermatoses. This method is as specific as PS, although it is less sensitive.

Background: Nasal device-related pressure ulcers are scarcely addressed in the literature.

Objective: To assess the prevalence and severity of cutaneous and mucosal nasogastric tube (NGT)-associated pressure ulcers (PU) in critically ill patients and to define predictors for their formation.

Methods: A single center observational study of intensive care unit patients with a NGT for more than 48 hours was conducted. Nasal skin was evaluated for PU. Ulcers were graded according to their depth. Consenting patients underwent a nasoendoscopic examination to evaluate intranasal mucosal injury.

Results: The study comprised 50 patients, 17 of whom underwent nasoendoscopic examination. Mean time of NGT presence in the nose was 11.3 ± 6.17 days. All patients had some degree of extranasal PU, 46% were low grade and 54% were high grade. Predictors for high grade extranasal PU compared to low grade PU were higher peak Sepsis-related Organ Failure Assessment (SOFA) scores (11.52 vs. 8.87, P = 0.009), higher peak C-reactive protein (CRP) levels (265.3 mg/L vs. 207.58, P = 0.008), and bacteremia (33.3% vs. 8.7%, P = 0.037). The columella was the anatomical site most commonly involved and the most severely affected. The number of intranasal findings and their severity were significantly higher in the nasal cavity containing the NGT compared to its contralateral counterpart (P = 0.039 for both).

Conclusions: NGTs cause injury to nasal skin and mucosa in critically ill patients. Patients with bacteremia, high CRP, and high SOFA scores are at risk for severe ulcers, warranting special monitoring and preventive measures.