Israel Medical Association Journal

Fibromyalgia syndrome is a chronic widespread musculoskeletal pain syndrome primarily characterized by fatigue, sleep disturbances, and cognitive impairment. Its etiology remains elusive despite ongoing research and has multifactorial elements. It has been shown that traumatic events and neuro-inflammation, autoimmunity, and genetic factors contribute to the pathogenesis of fibromyalgia syndrome.

Recent evidence has pointed to a bi-directional link between cardiovascular disease, traditional cardiovascular risk factors, and metabolic syndrome (MetS), together with the presence of fibromyalgia [1].

Background: The parasympathetic system and its main neurotransmitter, acetylcholine, contributes to homeostasis of inflammation. Cholinergic dysregulation is thought to contribute to the pathogenesis of inflammatory rheumatic diseases. Cholinesterase activity in patients with psoriatic arthritis (PsA) has not been investigated.

Objectives: To compare the cholinesterase activity in patients with PsA and immunocompetent controls and to explore the correlation between cholinergic status (CS) and PsA disease activity.

Methods: Serum acetylcholinesterase (AChE) and total cholinesterase activity were measured in patients with PsA (n=88) and matched controls (n=84). Cholinergic activity before and 3–6 months after the initiation of a biologic treatment was evaluated in seven patients with PsA.

Results: The levels of AChE and CS were similar in both PsA patients and controls. PsA patients treated with biologics had significantly lower levels of AChE and CS compared to patients treated with non-biologics: 447.4 vs. 526 substrate hydrolyzed/min/ml, P = 0.005, and 1360.9 vs. 1536, P = 0.029, respectively. We found an association between C-reactive protein levels, AChE activity (r = 0.291, P = 0.008), and cholinergic status (r = 0.247, P = 0.026) in patients with PsA but not in controls. No correlation between AChE activity, cholinergic status, and the indices of PsA disease activity was found. After initiating or switching biologic treatment in 7 patients, AChE levels remained stable.

Conclusions: We demonstrated similar cholinesterase activity in patients with psoriatic arthritis and controls, highlighting a potential effect of biologic treatment on cholinergic activity in patients with PsA.

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: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained.

Objectives: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study.

Methods: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI).

Results: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7–9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001).

Conclusions: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Background: Group A Streptococcus (GAS), the predominant bacterial pathogen of pharyngitis, is sometimes difficult to distinguish clinically from viral pharyngitis. Despite the high prevalence of viral pharyngitis in children, antibiotic treatment is common.

Objective: To investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with GAS pharyngitis (GAS-P) at a large pediatric community clinic.

Methods: Antibiotic prescription data were collected from October 2016 to March 2017 (pre-intervention period) and from October 2017 to March 2018 (post-intervention period). The intervention was a one-day seminar for primary care pediatricians on the diagnosis and treatment of GAS-P in children according to national guidelines.

Results: The overall prevalence of testing differed between the two time periods. There was a decrease in children who did not undergo any testing (from 68% to 63%), an increase in streptococcal rapid antigen detection testing (28% to 32%), and a slight increase in throat cultures (3% to 4%) (p = 0.02). There was no change in the types of antibiotics prescribed before and after the intervention (p = 0.152).

Conclusions: The ASP resulted in a slight reduction in the percentage of children who did not undergo laboratory testing for GAS-P and a slight reduction in the percentage of children who received antibiotic treatment. The ASP did not reduce the use of broad-spectrum antibiotics and macrolides.

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.

Background: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS).

Objectives: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores.

Methods: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted.

Results: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test.

Conclusions: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.

Germline pathogenic variants (PVs) in the RET proto-oncogene (OMIM 164761) are associated with a diverse phenotype based on the type of PV. Gain-of-function (GOF) PVs are associated with the highly penetrant multiple endocrine neoplasia type 2 (MEN2-OMIM 171400), which are hallmarked by an increased risk for developing medullary thyroid cancer (MTC), pheochromocytoma, and parathyroid adenomas. Loss-of-function (LOF) RET PVs are associated with incompletely penetrant Hirschsprung's disease (HSCR OMIM 142623), which are pathologically characterized by the absence of enteric ganglia affecting the distal colon and clinically manifest as neonatal intestinal obstruction. Despite anecdotal reports of familial clustering of neoplasms in HSCR families, mostly MEN2-associated tumors [1,2], HSCR is not considered to be associated with an increased risk for developing cancer [3]. We report on a family with an unusual multigenerational solid tumor phenotype and severe HSCR phenotype with a LOF RET PV.

Background: Cancellation of transesophageal echocardiography (TEE) tests leads to inefficient use of echocardiography laboratory (echo lab) time and wastes resources.

Objectives: To identify the causes of same-day TEE cancellations in hospitalized patients, to formulate a TEE order screening protocol, and to evaluate its efficacy at implementation.

Methods: We performed a prospective analysis of inpatients referred to a single tertiary hospital echo lab for TEE study by inpatient wards. A comprehensive screening protocol emphasizing active participation of all links directly involved in the chain of inpatient TEE referral was developed and implemented. Comparison of pre- and post-implementation of the new screening protocol on two consecutive periods of 6 months on TEE cancellation rates out of total ordered TEEs stratified by cause categories was performed.

Results: In total, 304 inpatient TEE procedures were ordered during the initial observation period; 54(17.8%) were canceled on the same day. The most common cancellation reasons were equally respiratory distress and patient not in fasted state (20.4% of total cancellations and 3.6% of all scheduled TEEs for each cause). Following implementation of the new screening process, total TEEs ordered (192) and cancelled (16) dropped significantly. A decrease in the rate of each cancellation category was observed, with statistical significance achieved for the overall cancellation rate (8.3% vs. 17.8%, P = 0.003), but not for the individual cancellation categories in split analysis.

Conclusions: A concerted effort to implement a comprehensive screening questionnaire significantly reduced same-day cancellations of scheduled TEEs.

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].

Background: Myalgic encephalomyelits/chronic fatigue syndrome (ME/CFS) is an acquired disease with symptoms of fatigue and pain. In pathogenesis, the induction of autoantibodies (AAB) against G-protein coupled receptors (GPCR), such as β-adrenergic receptors (β-AdR), has been suspected. GPCR-AAB correlate with symptom severity and autonomic dysfunction in ME/CFS.

Objectives: To describe symptoms and treatment of a patient presenting with infection-triggered ME/CFS demonstrating that levels of β-AdR-AAB underlie modulation over time, correlating with the severity of symptoms.

Methods: At T1 and T2, GPCR-AAB were measured and questionnaires assessing symptom severity were completed. TSHDS-IgM-AAB were tested, and SF density was analyzed via skin probe.

Results: At T2, elevated levels of β-AdR-AAB were found, corresponding with an aggravation of fatigue and pain symptoms. Elevated TSHDS-IgM-AAB were found, which corresponded with reduced fiber density from the skin probe.

Conclusions: The levels of β-AdR-AAB in post-infectious ME/CFS can be modulated. Future studies might target interventions to reduce these AAB.

Background: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units.

Objectives: To identify prognostic markers for AKI patients.

Methods: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study.

Results: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home.

Conclusions: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

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.