Israel Medical Association Journal

Background: Fibromyalgia syndrome (FMS) is estimated to affect 2–4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN.

Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls.

Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique.

Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013).

Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness.

Objective: To determine whether NAFLD is a risk factor for the severity of AC.

Methods: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria).

Results: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65–6.45, P = 0.038).

Conclusions: NAFLD is an independent risk factor for the severity of AC.

Background: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting.

Objectives: To examine the change in corneal and conjunctival sensation post-pterygium surgery.

Methods: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively.

Results: Nine patients participated in the study. Mean follow-up time was 9 months (9 ± 3.3, 6–12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation).

Conclusions: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

Background: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality.

Objective: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI.

Methods: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission.

Results: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithm_ebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis.

Conclusions: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Stevens-Johnson Syndrome (SJS), or toxic epidermal necrolysis, is a rare syndrome that develops after an allergic reaction to a medication [1,2]. It affects the skin and the mucocutaneous tissue. Individuals diagnosed with SJS are rarely referred to a rehabilitation medicine (RM) facility.

The annual prevalence of SJS is about one in one million. The skin is covered with blisters. Usually, it affects about 10 % of body surface area. The patients are treated usually by ophthalmologists, dermatologists, allergologists, and immunologists. When severe complications occur, plastic surgeons and intensive care physicians may also be involved. Few publications were found that linked SJS with comprehensive rehabilitation treatment [3-5].

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

Background: Omega-3 fatty acids promote fertility in males and females and constitute an important factor in the normal development of the fetus.

Objectives: We investigated the effect of omega-3 supplements during ovulation induction treatment in women with polycystic ovary syndrome (PCOS)-related infertility.

Methods: A randomized, double-blind study was conducted for 60 treatment cycles in 34 women with PCOS-related oligo/anovulation referred to the fertility clinic at the Bikur Cholim/Shaare Zedek Medical Center in Jerusalem, who underwent ovulation induction with clomiphene citrate (50 mg). Seventeen women (mean age 33.9 ± 0.9 years) received omega-3 supplements (3 × 600 mg/day) and 17 received placebo capsules (mean age 32.7 ± 0.9 years) for a maximum of two cycles. We recorded their characteristics and data from their serial hormonal blood tests and ultrasound examinations. We also conducted both univariate and multivariate analyses. The primary endpoint was conception.

Results: There were clinical pregnancies in 8/30 (26.7%) treatment cycles for women receiving omega-3 supplements versus 4/30 (13.3%) cycles with placebo. Among overweight/obese women (body mass index [BMI] 25–35), there were clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 (5.3%) with placebo (P < 0.04). For overweight/obese PCOS women, omega-3, lower BMI rates, and higher values of the endometrium’s thickness increased the odds of becoming pregnant. No harmful side effects from the omega-3 treatment were reported.

Conclusions: Omega-3 supplements demonstrated beneficial effects for fertility in women diagnosed with PCOS. Among the overweight/obese participants, the increased clinical pregnancy rate was significant.

Takotsubo syndrome (TTS) often develops following stressors such as cardiac surgery. It may be fatal in rare cases. Our 70-year-old female patient presented with a rare case of tricuspid valve papillary fibroelastoma, which was complicated by fatal TTS after successful resection. The patient had a right atrial mass that was investigated with computed tomography and transesophageal echocardiography (TTE). She was scheduled for surgery. Pathology findings were consistent with papillary fibroelastoma of the tricuspid valve. Three weeks after successful surgery, the patient was admitted due to cardiogenic shock with echocardiographic findings of apical ballooning and left ventricular outflow tract obstruction consistent with TTS. The patient died one hour after her admission despite optimal medical therapy.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacted global health, human behavior, economics, and even politics. Two years after the start of the pandemic, the scientific community was still learning about COVID-19 infections. One of the major lessons was the association between SARS-CoV-2 and diverse autoimmune manifestations, including multiple autoantibodies and various autoimmune diseases that developed in COVID-19 patients.

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

A 64-year-old male, with antineutrophil cytoplasmic antibody-associated vasculitis was being treated with methotrexate and low dose prednisone. He arrived at the clinic with bluish discoloration of the toes. Inflammatory markers and urine were normal. No history of chilblains or Raynoud's phenomena was noted. He recovered recently from mild coronavirus disease 2019 (COVID-19). A diagnosis of COVID toes (COVID digits) was made [Figure 1].

Coronavirus disease 2019 (COVID-19) affects different people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization. This case report presents a patient who had difficulty eradicating the corona virus due to being treated with rituximab, which depletes B lymphocytes and therefore disables the production of neutralizing antibodies. The regen-COV-2 antibody cocktail consists of two monoclonal antibodies, casirivimab and imdevimab. This cocktail successfully helped the patient's immune system eradicate the virus without auto specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production. In vitro studies confirm that eradication of the intact the virus. This case report emphases the importance of providing external antiviral antibodies regularly, like the regen-COV-2 antibody cocktail, as post- and even pre- SARS-CoV-2 infection prophylaxis in patients treated with rituximab.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.

Objectives: To evaluate the association of FMS with osteoporosis.

Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.

Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).

Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.

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.