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עמוד בית
Mon, 02.12.24

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September 2024
Aniela Shouval MD, Shiri Keret MD, Itzhak Rosner MD, Gleb Slobodin MD

The prevalence of difficult-to-treat rheumatoid arthritis (D2T RA) varies between 5% and 25%, with females comprising the majority of patients and no difference in patient age between D2T and non-D2T RA cohorts. While several attempts to subclassify D2T RA patients into defined subgroups have been tried, the inclusion of an individual D2T RA patient to one of the predefined subgroups can be difficult or impossible as multiple factors are usually involved in the mechanisms of rheumatoid arthritis (RA) refractoriness, with the complex interplay of inflammatory, structural, social, and psychological factors being unique for each patient. More severe disease at presentation, including seropositivity and early erosion formation, and insufficiently aggressive initial treatment can both contribute to the eventual development of D2T RA. No single test or study can replace the holistic clinical approach to the diagnosis and understanding of the causation of D2T RA. Traditional in-depth clinical history and thorough clinical examination remain sine qua non in managing D2T RA patients. Multifaceted contributions of inflammatory and non-inflammatory components create the uniqueness of D2T RA and dictate a comprehensive approach to the management, including both pharmacologic and non-pharmacological therapeutic strategies. Mean annual total costs for D2T RA patients have been estimated as being about twice as high as that of patients with non-D2T RA.

May 2024
Fadi Hassan MD, Mohammad E. Naffaa MD

Since the introduction of the international study group (ISG) criteria for the diagnosis of Behçet's disease (BD) in the early 1990s by Yazici and colleagues [1] and the international criteria for BD (ICBD) by Davatchi and colleagues in 2014 [2], great progress has been achieved in the diagnosis of BD with fairly high sensitivity and specificity rates. However, a small, but very challenging and unique minority might not fulfill these criteria, at least at presentation. These patients are most challenging as they may present with life-threatening vascular or neurological manifestations. If the diagnosis BD is delayed, the risk for morbidity and even mortality might be increased. Therefore, we should aim for early diagnosis and prompt treatment.

January 2024
Forsan Jahshan MD, Tal Marshak MD, Jamal Qarawany MD, Boaz Markel MD, Amiel Sberro MD, Yonatan Lahav MD, Eli Layous MD, Netanel Eisenbach MD, Isaac Shochat MD, Eyal Sela MD, Ohad Ronen MD

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.

October 2023
Moran Drucker Iarovich MD, Sara Apter MD, Eli Konen MD MHA, Yael Inbar MD, Marrianne Michal Amitai MD, Eyal Klang MD

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.

George Shallufi MD, Suhair Hanna MD, Asaad Khoury MD, Tarek Saadi MD, Anat Ilivitzki MD, Michal Gur MD, Lea Bentur MD, Ronen Bar-Yoseph MD

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.

September 2023
Shiri Keret MD, Aniela Shouval MD, Itzhak Rosner MD, Doron Rimar MD, Michael Lurie MD, Gleb Slobodin MD

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.

August 2023
Andre Keren MD, Rabea Asleh MD PhD MHA, Edo Y. Birati MD, Tuvia Ben Gal MD, Michael Arad MD

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.

Michal M. Amitai MD, Nadin Kanaan MD, Shelly Soffer MD, Lee Alper, Noa Rozendorn MD, Daniel Jacob Harrington, Uri Kopylov MD, Adi Lahat MD, Doron Yablecovitch MD, Rami Eliakim MD, Shomron Ben-Horin MD, Eyal Klang MD

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.

July 2023
Aaron Hanukoglu MD, Dorit Lev MD

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.

May 2023
Moran Gawie-Rotman MD, Alon Shrim MD, Ester Maor-Sagie MD, Noa Haggiag MD, Rinat Gabbay-Benziv MD, Mordechai Hallak MD

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.

Aviv Schupper MD, Galia Barash MD, Lilach Benyamini MD, Revital Ben-Haim MD, Eli Heyman MD, Eli Lahat MD, Haim Bassan MD

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.

April 2023
Moshe Herskovitz MD

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.

Yishai Mintzker MD, Limor Adler MD, Linoy Gabay MPH, Tamar Banon MSc

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.

February 2023
Aviv Barzilai MD MSc, Hila Greenbaum MD MPH, Monica Huszar MD, Sergei Ikher MD, Avner Shemer MD, Sharon Baum MD

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.

Yarden Tenenbaum Weiss MD, Michael Friger PhD, Alon Haim MD, Eli Hershkovitz MD

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.

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