Israel Medical Association Journal

Ovarian cancer is a major cause of cancer death among women worldwide, and particularly in Israel. Although the disease at stage IA has 5 year survival rates of over 90%, early detection methods are not sufficiently accurate. Consequently, ovarian cancer is typically diagnosed late, which results in high fatality rates. An excellent candidate for early ovarian cancer detection would be in vivo magnetic resonance spectroscopy (MRS) because it is non-invasive and free of ionizing radiation. In addition, it potentially identifies metabolic features of cancer. Detecting these metabolic features depends on adequate processing of encoded MRS time signals for reconstructing interpretable information. The conventional Fourier-based method currently used in all clinical scanners is inadequate for this task. Thus, cancerous and benign ovarian lesions are not well distinguished. Advanced signal processing, such as the fast Padé transform (FPT) with high-resolution and clinically reliable quantification, is needed. The effectiveness of the FPT was demonstrated in proof-of-concept studies on noise-controlled MRS data associated with benign and cancerous ovaries. The FPT has now been successfully applied to MRS time signals encoded in vivo from a borderline serous cystic ovarian tumor. Noise was effectively separated out to identify and quantify genuine spectral constituents that are densely packed and often overlapping. Among these spectral constituents are recognized and possible cancer biomarkers including phosphocholine, choline, isoleucine, valine, lactate, threonine, alanine, and myoinositol. Most of these resonances remain undetected with Fourier-based in vivo MRS of the ovary. With Padé optimization, in vivo MRS could become a key method for assessing ovarian lesions, more effectively detecting ovarian cancer early, thereby improving survival for women afflicted with this malignancy.

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

Background: Patients with giant cell arteritis (GCA) suffer from inflammatory diseases often treated by large amounts of corticosteroids. Whether this inflammatory burden also carries an increased risk for cardiovascular morbidity, and especially ischemic heart disease, is not clearly established.

Objectives: To clarify the linkage between GCA and ischemic heart disease. 

Methods: In a cross-sectional study, we assessed the association between GCA and ischemic heart disease, adjusting for cardiovascular risk factors, among GCA patients and matched controls using the database of the largest healthcare provider in Israel.

Results: The study group was comprised of 5659 GCA patients and 28,261 age and gender matched controls. The proportion of ischemic heart disease was higher in the GCA group (27.5% vs. 12.5% among controls, odds ratio 2.65). Diabetes mellitus, hypertension, hyperlipidemia and smoking were also found to have higher concurrency in GCA. After stratifying for those cardiovascular co-morbidities using logistic regression, GCA remained independently associated with ischemic heart disease with an odds ratio of 1.247 (1.146–1.357 P < 0.001).

Conclusions: GCA is associated with both cardiovascular risk factors and ischemic heart disease. Healthcare professionals should not overlook this aspect of the disease when managing GCA patients. 

 

Background: The evidence on the use of dexamethasone implants in the treatment of Behçet’s disease (BD)-related uveitis is limited to a few cases. 

Objectives: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. 

Methods: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits.

Results: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. 

Conclusions: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.

 

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immune deficiency of adulthood. Besides recurrent infections, autoimmune disorders–mainly cytopenias–affect 30% of patients with CVID.

Objectives: To describe the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIg), which is a combination of 10% [human] SCIg with recombinant human hyaluronidase for the treatment of CVID-linked cytopenias. 

Methods: We describe four women (mean age 54 years) with CVID associated with idiopathic thrombocytopenic purpura (ITP) (n=3) and autoimmune hemolytic anemia (AIHA) (n=1). Diagnosis of CVID was made according to the European Society of Immune Deficiencies / Pan-American Group for Immune Deficiency criteria. All were treated with fSCIg (bi-monthly, 20 g).

Results: After a median follow-up of 22 months, all patients achieved a stable remission from the cytopenias, characterized by increased platelet values in ITP (mean values 93000/mmc), and resolution of anemia. A reduction of the daily prednisone dose was documented in the patient with AIHA. No systemic adverse drug reactions were observed. 

Conclusions: Our preliminary data documented the efficacy and safety of fSCIg in the treatment of CVID associated with autoimmune cytopenias, with a good tolerability. We also noted the role of fSCIg as a steroid sparing agent. It is thus possible to suppose an immunomodulatory role for fSCIg, but linked to different mechanisms than IVIg, due to the peculiar pharmacokinetic and administration route of fSCIg. 

 

Background: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture’s disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture’s disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis.

Objectives: To assess the predictive value of positive anti-GBM antibodies in a clinical setting. 

Methods: Data from anti-GBM antibody tests performed at one medical center between 2006 and 2016 were systematically and retrospectively retrieved. We recruited 1914 patients for the study. Continuous variables were computed as mean ± standard deviation, while categorical variables were recorded as percentages where appropriate. Sensitivity and specificity of anti-GBM titers were calculated. Kaplan–Meyer analysis was performed, stratifying survival according to the anti-GBM antibody titers.

Results: Of the 1914 anti-GBM test results detected, 42 were positive, 23 were borderline, 142 were excluded, and 1707 results were negative. Male-to-female ratio was 1:1.2. Sensitivity of anti-GBM test was 41.2% while specificity was 85.4%. Concerning the Kaplan–Meyer analysis, overall survival was 1163.36 ± 180.32 days (median 1058 days). 

Conclusions: Our study highlights the lack of sensitivity of serological testing of anti-GBM titers. Comparing survival curves, the survival correlated with anti-GBM titer only in a borderline way. Because highly sensitive bioassays are not routinely used in clinics, renal biopsy is still pivotal for Goodpasture’s disease diagnosis.

 

Background: Leakage from the staple line is the most serious complication encountered after sleeve gastrectomy, occurring in 2.4% of surgeries. The use of inappropriately sized staplers, because of variability in stomach wall thickness, is a major cause of leakage.

Objectives: To measure stomach wall thickness across different stomach zones to identify variables correlating with thickness.

Methods: The study comprised 100 patients (52 females). Stomach wall thickness was measured immediately after surgery using a digital caliper at the antrum, body, and fundus. Results were correlated with body mass index (BMI), age, gender, and pre-surgical diagnosis of diabetes, hypertension, hyperlipidemia and fatty liver.

Results: Stomach thickness was found to be 5.1 ± 0.6 mm at the antrum, 4.1 ± 0.6 mm at the body, and 2. 6 ± 0.5 mm at the fundus. No correlation was found between stomach wall thickness and BMI, gender, or co-morbidities. 

Conclusions: Stomach wall thickness increases gradually from the fundus toward the antrum. Application of the correct staple height during sleeve gastrectomy is important and may, theoretically, prevent leaks. Staplers should be chosen according to the thickness of the tissue.

 

Background: Standardization of the dietetic care process allows for early identification of malnutrition and metabolic disorders, interdisciplinary collaboration among the medical team, and improved quality of patient care. Globally, dietitians are adopting a nutrition care model that integrates national regulations with professional scope of practice. Currently, Israel lacks a standardized dietetic care process and documentation terminology.

Objectives: To assess the utilization of a novel sectoral documentation system for nutrition care in Israel.

Methods: Seventy dietitians working in 63 geriatric facilities completed an online training program presenting the proposed patient-sectoral-model. Training was followed by submission of sample case studies from clinical practice or completion of a case simulation. Application of the proposed model was assessed by measuring the frequency participants implemented different sections of the model and responses to an approval questionnaire.

Results: Fifty-four participants (77%) provided completed cases. Over 80% of participants reported each step of the proposed dietary care process with 100% reporting the “nutrition diagnosis”. Fifty-one dietitians (72.8%) completed the approval survey with the section on nutrition diagnosis receiving a highly favorable response (95%), indicating that the new documentation system was beneficial. Over 80% of participants rated the model useful in clinical practice.

Conclusions: A sectoral approach for documenting dietetic care may be the ideal model for dietitians working in specific patient populations with the potential for improving interdisciplinary collaboration in patient care.

Background: While patients presenting to emergency departments (ER) with chest pain are increasingly managed in chest pain units (CPU) that utilize accelerated diagnostic protocols for risk stratification, such as single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), data are lacking regarding the prognostic implications of mildly abnormal scans in this population.

Objectives: To evaluate the prognostic implications of mildly abnormal SPECT MPI results in patients with acute chest pain.

Methods: Of the 3753 chest pain patients admitted to the CPU at the Leviev Heart Center, Sheba Medical Center 1593 were further evaluated by SPECT MPI. Scans were scored by extent and severity of stress-induced perfusion defects, with 1221 patients classified as normal, 82 with myocardial infarction without ischemia, 236 with mild ischemia, and 54 with more than mild ischemia. Mild ischemia patients were further classified to those who did and did not undergo coronary angiography within 7 days.

Results: Mild ischemia patients who underwent coronary angiography were more likely to be male (92% vs. 81%, P = 0.01) and to have left anterior descending ischemia (67% vs. 42%, P = 0.004). After 50 months, these patients returned less often to the ER with chest pain (53% vs. 87%, P < 0.001) and had a lower combined endpoint of acute coronary syndrome and death (8% vs. 16%, P < 0.001).

Conclusions: Compared to patients with chronic stable angina, patients presenting with acute chest pain exhibiting mildly abnormal SPECT MPI findings should perhaps undergo a more aggressive diagnostic and therapeutic approach.

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.