Israel Medical Association Journal

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in Caucasian adults. Most patients have good renal prognosis, but 30–40% may progress to end stage renal disease (ESRD). 

Objectives: To evaluate the efficacy and safety of immunosuppressive treatment (IST) in high-risk patients.

Methods: All IMN patients diagnosed by kidney biopsy from 2004–2010 were included. Clinical and laboratory data were collected at each follow-up visit. Risk assessment for renal progression classified patients as high risk if: 24 hour protein excretion > 6 g/day, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and severe disabling or life-threatening clinical symptoms of NS were present.

Results: Among 290 biopsies, 37 patients (12.7%) were IMN. They were allocated to the high-risk IST group (n=16) or low-risk supportive treatment (ST) group (n=21) according to the likelihood of developing renal failure. Mean follow-up was 47 ± 17.3 months. Complete and partial remission rate was 68.7% for high-risk IST vs. 90.4% for low-risk ST. In the high-risk IST group, eGFR was significantly lower at 30 months (65.5 ± 28.6 vs. 85.3 ± 21.6 at baseline, P < 0.05). Four high-risk patients reached ESRD. In the low-risk ST group, eGFR remained stable at 30 and 60 months. 

Conclusions: This study showed a high remission rate for IMN. IST with prednisolone and cyclophosphamide provided favorable renal outcomes in most high-risk patients. The very high remission rate obtained in the low-risk patients confirms the adequacy of supportive treatment in this group.

Upper extremity deep vein thrombosis (UEDVT) is defined as thrombosis of the deep venous system (subclavian, axillary, brachial, ulnar, and radial veins), which drains the upper extremities. It can be caused by thoracic outlet anatomic obstruction, such as Paget–Schroetter syndrome, (primary) or by central intravenous catheters (secondary). UEDVT may be asymptomatic or present with acute severe pain and arm swelling. Clinical suspicion should be confirmed by diagnostic imaging procedures such as duplex ultrasound, computed tomography scan, or magnetic resonance imaging. UEDVT is managed by anticoagulant treatment. In addition to that, early thrombolysis aimed at preventing post-deep vein thrombosis syndrome and thoracic outlet decompression surgery should be given to patients with primary UEDVT. Anticoagulation without thrombolysis is the treatment of choice for patients with catheter-related thrombosis. Mandatory functioning catheters can remain in place with anticoagulant treatment. All other catheters should be immediately removed. The management of patients with UEDVT requires an experience multidisciplinary team comprised of internists, radiologists, hematologists, and vascular surgeons. Understanding the risk factors for the development of UEDVT, the diagnostic procedures, and the treatment modalities will improve the outcome of those patients.

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy).

Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery.

Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan–Meier method.

Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50–62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52–87%), LC was 84% (95%CI 65–93), and DFS 35% (95%CI 14–59). Grade 4–5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01).

Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Background: Computed tomography (CT) brain perfusion is a relatively new imaging method that can be used to differentiate patients following epileptic seizures in the setting of acute neurological deficits (e.g., hemiparesis, hemiplegia, hemianopsia, aphasia) who arrive at the emergency room with a suspected stroke.

Objectives: To evaluate brain perfusion changes in patients who had an epileptic seizure.

Methods: We retrospectively identified 721 patients who presented at our stroke center between 2012 and 2015 with a suspected acute stroke and underwent examination thorough a stroke protocol, including cerebral CT perfusion (CTP) and CT angiography (CTA) within 8 hours from the onset of symptoms. 

Results: Out of 721 patients, 25 presented with ictal electroencephalography (EEG) findings within 24–72 hours from symptom onset without evidence of vascular occlusion on CTA. While 15 patients had to be excluded from the study due to concomitant brain pathology, we found a specific reduction in cerebral blood volume and cerebral blood flow occurring at the ictal zone, which was identified by a post hoc EEG investigation. 

Conclusions: Our study shows that CTP is an easily accessible tool in emergency department setting for the detection of changes in blood flow dynamics among postictal patients. Thus, we propose the use of CTP in emergency settings to discriminate between postictal changes and acute vascular events. 

 

Background: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases.

Objectives: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype.

Methods: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. 

Results: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05).

Conclusions: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.

 

Background: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation. 

Objectives: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester.

Methods: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded.

Results: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05). 

Conclusions: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

 

Background: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. 

Objectives: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients.

Methods: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only.

Results: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12).

Conclusions: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.

 

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the “real-life” safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3–4 months. Adverse events were obtained from patients’ medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1–7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Background: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. 

Objectives: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function.

Methods: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed.

Results: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). 

Conclusions: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

 

Background: Upper respiratory tract infection (URTI) occurs frequently in the general population and is considered a benign self-limited disease. Dialysis patients constitute a high risk population whose morbidity and mortality rate as a result of URTI is unknown. 

Objectives: To assess the local incidence, morbidity and mortality of URTI in dialysis patients compared to the general population. 

Methods: In this retrospective cohort study we reviewed the charts of all chronic dialysis patients diagnosed with URTI at Meir Medical Center, Kfar Saba, Israel during the 2014–2015 winter season. 

Results: Among 185 dialysis patients, 40 were found to be eligible for the study. The average age was 66.1 ± 15.7 years, and the co-morbidity index was high. Influenza A was the most common pathogen found, followed by rhinovirus, respiratory syncytial virus and para-influenza. Of the 40 patients 21 (52.5%) developed complications: pneumonia in 20%, hospitalization in 47.5%, and respiratory failure requiring mechanical ventilation in 12.5%. Overall mortality was 10%. General population data during the same seasonal period showed a peak pneumonia incidence of 4.4% compared to 20% in the study population (P < 0.0001). 

Conclusions: The study findings show that compared to the general population, URTI in dialysis patients is a much more severe disease and has a higher complication rate. Influenza A, the most common pathogen, is associated with a worse prognosis. 

 

Background: Fine-needle aspiration cytology (FNAC) is used to provide rapid diagnostic information regarding masses of the head and neck. To achieve good results, adequate training is essential.

Objectives: To evaluate the efficacy of FNAC in the diagnosis of head and neck masses performed by residents and attending physicians.

Methods: Palpable guided FNA biopsies from 166 consecutive patients with head and neck masses, excluding thyroid, who were treated in our department between 2008 and 2010 were retrospectively reviewed. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated.

Results: A total of 193 FNACs were performed in 161 patients (5 patients were excluded due to age under 18). Mean age was 57.3 years; female to male ratio was approximately 5:4. Most FNACs were performed in masses in the parotid gland (37.3%), 14.5% in the posterior neck, 19.1% in the lateral neck, 15% at level 1, and 9.3% at level 6. The median size of the masses aspirated was 2 cm. Most FNACs were performed by an experienced physician (2.5:1). About 25% of the patients required a second FNAC. Almost 70% of FNACs were diagnostic. Of these, 71.2% were of benign processes and 28.8% of malignancies.

Conclusions: An FNAC of a palpable mass in all sites of the neck, excluding the thyroid, can be done as an office procedure with reasonable results without imaging guidance. About 25% of patients will require another biopsy. The procedure is not difficult to master, as evident by the fact that there were no differences in the results of FNACs performed by an attending otolaryngologist or a resident.