Israel Medical Association Journal

Background: Laryngopharyngeal reflux (LPR) refers to the backflow of acidic stomach content into the larynx, pharynx, and upper aerodigestive tract. The diagnosis of LPR is based on the patient's history and findings of the laryngoscopy associated with LPR. Other possible manifestations consistent with LPR symptoms include laryngeal cancer, vocal fold granulomas, Reinke's space edema, and vocal polyps. In this study, we compared the characteristics of patients with LPR symptoms and incidental laryngeal findings (ILF) in the laryngoscopic evaluation to those without ILF (WILF).

Objectives: Determine the characteristics of LPR-symptomatic patients with ILF versus WILF.

Methods: In this retrospective study, we examined 160 medical charts from patients referred to the otolaryngology clinic at Galilee Medical Center for LPR evaluation 2016–2018. The reflux symptoms index (RSI), reflux finding score (RFS), and demographics of the patient were collected. All patients with a positive RSI score for LPR (RSI > 9) were included, and the profiles of patients with versus without ILF on laryngoscopy examination were compared.

Results: Of the 160 patients, 20 (12.5%) had ILF during laryngoscopy. Most had vocal cord findings such as leukoplakia (20%), polyps (15%), and nodules (20%). Hoarseness, throat clearing, swallowing difficulty, breathing difficulties, and total RSI score were significantly higher in patients with ILF.

Conclusions: Evaluation of LPR symptoms may provide otolaryngologists with a tool to identify patients with other findings on fiberoptic laryngoscopy. A laryngoscopic examination should be part of the examination of every patient with LPR to enable diagnosis of incidental findings.

Background: Computed tomography (CT) is the main diagnostic modality for detecting pancreatic adenocarcinoma.

Objectives: To assess the frequency of missed pancreatic adenocarcinoma on CT scans according to different CT protocols.

Methods: The medical records of consecutive pancreatic adenocarcinoma patients were retrospectively collected (12/2011–12/2015). Patients with abdominal CT scans performed up to a year prior to cancer diagnosis were included. Two radiologists registered the presence of radiological signs of missed cancers. The frequency of missed cancers was compared between portal and pancreatic/triphasic CT protocols.

Results: Overall, 180 CT scans of pancreatic adenocarcinoma patients performed prior to cancer diagnosis were retrieved; 126/180 (70.0%) were conducted using pancreatic/triphasic protocols and 54/180 (30.0%) used portal protocols. The overall frequency of missed cancers was 6/180 (3.3%) in our study population. The frequency of missed cancers was higher with the portal CT protocols compared to the pancreatic/triphasic protocols: 5/54 (9.3%) vs. 1/126 (0.8%), P = 0.01. CT signs of missed cancers included small hypodense lesions, peri-pancreatic fat stranding, and dilated pancreatic duct with a cut-off sign.

Conclusions: The frequency of missed pancreatic adenocarcinoma is higher on portal CT protocols. Physicians should consider the cancer miss rate on different CT protocols.

Common variable immunodeficiency (CVID) is a heterogeneous primary immune deficiency disorder characterized mainly by defective B lymphocyte differentiation, leading to hypogammaglobinemia and defective antibody production. It is often combined with cellular immune defects. A minority of patients present during childhood and adolescence. Infections are most often sinopulmonary but can affect any system. The noninfectious complications include progressive lung disease, autoimmunity, gastrointestinal inflammatory disease, liver disease, granulomatous disease, lymphoid hyperplasia and infiltrative disease, and the development of lymphoma and other cancers. In addition to recurrent infections and bronchiectasis, patients may develop chronic interstitial lung disease, granulomatous lung disease, lymphoma, and pulmonary hypertension.

Idiopathic inflammatory myopathies (IIM) are a group of rare, autoimmune, systemic diseases with a large spectrum of clinical phenotypes. The diagnosis and management of myositis demand an integrated evaluation of different clinical, laboratory, and pathological findings in various organs. Recent developments in IIM research, especially in the serological testing and pathology fields, has led to a new classification and better recognition of patients with early or extra-muscular disease, with improvement in clinical care and prognosis.

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

Background: Jejunal disease is associated with worse prognosis in Crohn's disease. The added value of diffusion weighted imaging for evaluating jejunal inflammation related to Crohn's Disease is scarce.

Objectives: To compare diffusion weighted imaging, video capsule endoscopy, and inflammatory biomarkers in the assessment of Crohn's disease involving the jejunum.

Methods: Crohn's disease patients in clinical remission were prospectively recruited and underwent magnetic resonance (MR)-enterography and video capsule endoscopy. C-reactive protein and fecal-calprotectin levels were obtained. MR-enterography images were evaluated for restricted diffusion, and apparent diffusion coefficient values were measured. The video capsule endoscopy-based Lewis score was calculated. Associations between diffusion weighted imaging, apparent diffusion coefficient, Lewis score, and inflammatory biomarkers were evaluated.

Results: The study included 51 patients, and 27/51 (52.9%) with video capsule endoscopies showed jejunal mucosal inflammation. Sensitivity and specificity of restricted diffusion for video capsule endoscopy mucosal inflammation were 59.3% and 37.5% for the first reader, and 66.7% and 37.5% for the second reader, respectively. Diffusion weighted imaging was not statistically associated with jejunal video capsule endoscopy inflammation (P = 0.813).

Conclusions: Diffusion weighted imaging was not an effective test for evaluation of jejunal inflammation as seen by video capsule endoscopy in patients with quiescent Crohn's disease.

Children affected with Poland syndrome are born with missing or underdeveloped muscles (typically pectoralis major) on one side of the body. Breast abnormalities such as unilateral hypoplasia or agenesis of the breast and nipple may also occur. Other muscles on the affected side, including other muscles in the chest wall, shoulder, arm, and hand, may be missing or underdeveloped [1]. Ribs may be noticeable due to the loss of subcutaneous fat. Sparse or absent axillary and pectoral hairs are a common manifestation of this syndrome.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

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: Loss of consciousness (LOC) is one of the most common reasons for seeking neurological advice in clinics and emergency departments. There is considerable difficulty in determining the nature of the events according to patient reports, and collateral history is often difficult to interpret due to multiple versions and observer interpretations.

Objectives: To examine the utility and validity of incidental video recordings (IVR) in the differential diagnosis of LOC.

Methods: In this retrospective study, I included patients with a documented IVR description. Results were divided into three categories: definite approval (IVR conclusion was decisive and congruent with the gold standard test), partial approval (IVR conclusion was decisive and diagnosis was confirmed by treatment response or clinical course), and inconclusive (IVR conclusion was not decisive, no gold standard test was performed, or the gold standard test was either not decisive or incongruent with the IVR).

Results: I evaluated the results of 31 patients with IVR documentation. Overall, in 18 patients (58%), the IVR conclusion was decisive and congruent with the gold standard test. In 8 patients (25.8%), the IVR conclusion was decisive and congruent with the clinical course or treatment response. In 5 patients (16.1%) the IVR was regarded as inconclusive.

Conclusions: IVR have a substantial yield and are highly accurate in the differential diagnosis of LOC, mainly differentiating between epileptic seizures and psychogenic nonepileptic seizures, yet it is utilized in a minority of the patients in real life.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

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: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children.

Objectives: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain.

Methods: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2–18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts.

Results: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS.

Conclusions: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

Background: Acute mesenteric ischemia (AMI) is a medical condition with high levels of morbidity and mortality. However, most patients suspected of AMI will eventually have a different diagnosis. Nevertheless, these patients have a high risk for co-morbidities.

Objectives: To analyze patients with suspected AMI with an alternative final diagnosis, and to evaluate a machine learning algorithm for prognosis prediction in this population.

Methods: In a retrospective search, we retrieved patient charts of those who underwent computed tomography angiography (CTA) for suspected AMI between January 2012 and December 2015. Non-AMI patients were defined as patients with negative CTA and a final clinical diagnosis other than AMI. Correlation of past medical history, laboratory values, and mortality rates were evaluated. We evaluated gradient boosting (XGBoost) model for mortality prediction.

Results: The non-AMI group comprised 325 patients. The two most common groups of diseases included gastrointestinal (33%) and biliary-pancreatic diseases (27%). Mortality rate was 24.6% for the entire cohort. Medical history of chronic kidney disease (CKD) had higher risk for mortality (odds ratio 2.2). Laboratory studies revealed that lactate dehydrogenase (LDH) had the highest diagnostic ability for predicting mortality in the entire cohort (AUC 0.70). The gradient boosting model showed an area under the curve of 0.82 for predicting mortality.

Conclusions: Patients with suspected AMI with an alternative final diagnosis showed a 25% mortality rate. A past medical history of CKD and elevated LDH were associated with increased mortality. Non-linear machine learning algorithms can augment single variable inputs for predicting mortality.

Hypereosinophilia is defined as the absolute eosinophilic count of above 1500 cells/µL in the peripheral blood on two separate tests taken during one month and/or the pathological confirmation of hypereosinophilia. There are many conditions that are associated with increased eosinophil counts including: parasitic infections, drug reactions, eosinophilic granulomatosis with polyangiitis, allergic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS), primary immunodeficiencies (PID), eosinophilic gastrointestinal diseases (EGID), familial hypereosinophilia, and neoplasms [1]. Molecular classification may be an adjuvant in the classification of hypereosinophilia [2]. Our patient presented with hypereosinophilia as part of a paraneoplastic syndrome.