Israel Medical Association Journal

Background: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.

Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.

Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.

Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).

Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.

Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.

Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.

Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).

Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.

Background: Opinions differ as to the need of a lateral radiograph for diagnosing community acquired pneumonia in children referred to the emergency department. A lateral radiograph increases the ionizing radiation burden but at the same time may improve specificity and sensitivity in this population.

Objectives: To determine the value of the frontal and lateral chest radiographs compared to frontal view stand-alone images for the management of children with suspected community acquired pneumonia seen in a pediatric emergency department.

Methods: Chest radiographs from 451 children with clinically suspected pneumonia were retrospectively reviewed. Interpretation of frontal views was compared to interpretation of combined frontal and lateral view, the latter being the gold standard.

Results: Findings consistent with bacterial pneumonia were diagnosed in 94 (20.8%) of the frontal stand-alone radiographs and in 109 (24.2%) of the combined frontal and lateral radiographs. The sensitivity, specificity, positive predictive value, and negative predictive value of the frontal radiograph alone were 86.2%, 93.9%, 81.7%, and 95.5%, respectively. False positive and false negative rates were 15% and 21%, respectively, for the frontal view alone. The number of lateral radiographs needed to diagnose one community acquired pneumonia was 29.

Conclusions: The lateral chest radiograph improves the diagnosis of pediatric community acquired pneumonia to a certain degree and may prevent overtreatment with antibiotics.

Background: Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used “gold standard” tests.

Objectives: To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas.

Methods: A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report.

Results: All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases.

Conclusions: Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.

Background: Survival of patients who were discharged from the hospital following out-of-hospital cardiac arrest (OHCA) has not been well defined.

Objective: To verify predictor variables for prognosis of patients following OHCA who survived hospitalization.

Methods: We retrospectively reviewed clinical, demographic, and outcome data of consecutive patients who were hospitalized from January 1, 2009, through December 31, 2014, into the intensive coronary care unit (ICCU) after aborted OHCA and discharged alive. The patients were followed until December 31, 2015.

Results: Of the 180 patients who were admitted into ICCU after OHCA, 64 were discharged alive (59.3%): 55 were male (85.9%), 14 died 16.5 ± 18 months after their discharge. During 1 year follow-up, nine patients (14.1%) died after a median period of 5.5 months and 55 patients (85.9 %) survived. Diabetes mellitus and chronic renal failure (CRF) were more frequent in patients who died within 1 year after their hospital discharge than those who survived. Ventricular fibrillation, such as initial arrhythmia, and opening of occluded infarct related artery were more frequent in survivors.

Conclusions: Most of the patients who were discharged after OHCA were alive at the 1 year follow-up. The risk of death of cardiac arrest survivors is greatest during the first year after discharge. CRF remains a poor long-term prognostic factor beyond the patients' discharge. Ventricular fibrillation, as initial arrhythmia, and opening of occluded infarct related artery have a positive impact on long-term survival.

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm³. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

Background: Invasive cervical cancer is caused by human papillomavirus (HPV).

Objectives: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.

Methods: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006–2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).

Results: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.

Conclusions: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

Dupuytren’s disease is a common benign fibromatosis of the palmar and digital fascia. The exact pathophysiology and epidemiology of this condition have not been entirely identified. Pathologic fibrous bands cause a flexion contracture of the metacarpal phalangeal joints and proximal interphalangeal joint. Treatment includes fasciectomy, needle fasciotomy, and enzymatic fasciectomy.

Background: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs).

Objectives: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. 

Methods: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded.

Results: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6–12 months follow-up. 

Conclusions: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

 

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. However, a subgroup of patients experiences extraglandular manifestations which worsens disease prognosis. To date evidence based guidelines for the management of pSS are lacking, hence the therapeutic approach is mainly based on expert opinion and data from other connective tissue diseases. In recent years, several studies have explored the efficacy and safety of biologic agents in pSS and after the failure of tumor necrosis factor inhibitors, the attention has been focused on compounds directly targeting B or T lymphocytes. The aim of this review article is to provide an overview of available data about B and T cell targeting in pSS and of future directions based on ongoing trials.