Israel Medical Association Journal

Background: Patients with rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS), encounter significantly higher rates of cardiovascular morbidity and mortality. The renin-angiotensin-aldosterone system maintains hemodynamic stability through blood pressure regulation. When dysregulated, this system has been implicated in various pathological conditions, including cardiovascular events.

Objectives: To investigate the levels of renin and aldosterone in RA and AS patients.

Methods: Three groups were recruited: patients with RA, patients with AS, and healthy controls. Subjects were excluded if they had a diagnosis of hypertension, hyperaldosteronism, or renal artery stenosis, or were taking drugs that might have affected renin levels. Renin and aldosterone levels were measured using commercially available kits. Data were analyzed using univariate analyses and multivariate regression analyses.

Results: Fifty-one subjects were enrolled in the study: 15 with RA, 4 with AS, and 32 healthy controls. At the univariate analysis, the three groups differed in age (P = 0.005), renin levels (P = 0.013), and aldosterone-to-renin ratio (P = 0.019). At the post-hoc tests, both AS and RA patients differed from controls for renin levels and the aldosterone-to-renin ratio. At the multivariate regression analysis, AS patients had lower renin values than controls (beta standardized regression coefficient -0.323, P = 0.022).

Conclusion: Patients with RA tended to have lower levels of plasma renin compared to healthy subjects. This finding indicates that the renin-angiotensin-aldosterone system might not be directly involved in the process that results in increased cardiovascular events in rheumatoid arthritis.

Background: Thymectomy is a reliable surgical method for treating patients with myasthenia gravis (MG) and benign tumors of the thymus. Despite the advantages of minimally invasive surgical approaches for resection of thymic neoplasms, there are still controversies regarding the superiority of one type of surgery over another.

Objectives: To report the results of our initial Israeli experience with robotic thymectomy in 22 patients with MG and suspected benign thymic tumors.

Methods: We retrospectively analyzed 22 patients (10 men, 12 women) who underwent robotic thymectomy by a left-sided (16) or right-sided approach (6) using the da Vinci robotic system at Assaf Harofeh Medical Center. Seven patients were diagnosed with MG before surgery and 14 had suspected benign thymic neoplasms.

Results: Average operative time was 90 minutes. There were no deaths or intraoperative complications. Postoperative complications occurred in two patients (dyspnea and pleural effusion). Median blood loss was 12.3 cc (range 5–35 cc), median hospital stay 2.9 days (range 2–5 days), and mean weight of resected thymus 32.1 grams. Seven patients had thymic hyperplasia, six a lipothymoma, one a thymic cyst. Seven each had thymomas in different stages and one had a cavernous hemangioma.

Conclusions: Robotic thymectomy is a safe, technically effective surgical method for resection of thymic neoplasms. The advantages of this technique are safety, short hospitalization period, little blood loss, and low complications. We have included this surgical procedure in our thoracic surgery residency program and recommend a learning curve program of 10 to 12 procedures during residency.

Background: Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear.

Objectives: To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT.

Methods: We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann–Whitney was applied to determine the correlation between MTD and IF.

Results: Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF.

Conclusions: IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.

Background: Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared.

Objectives: To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy.

Methods: Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist.

Results: Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance.

Conclusions: Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.

Background: Pacemaker pocket early post-implantation inflammation (EPII) is defined as clinical signs of local erythema without any systemic signs of infection occurring early after implantation. Data on the best treatment regimen for apparent superficial EPII is scarce. 

Objectives: To investigate the prognostic value of medical treatment, rather than extraction surgery, in patients with EPII. 

Methods: Data from 6013 consecutive patients who underwent cardiac implantable electronic device (CIED) implantation or replacement from 2007–2015 were retrospectively analyzed; 40 (0.7%) presented with EPII. Our goal was the absence of major complications and to avoidance of extraction. 

Results: Patients with EPII were initially treated medically. Nineteen (47%) (group A) recovered with antibiotic treatment only. In the other 21 patients (53%) (group B), CIED extraction was performed. Group B had more major complications compared to group A (15 [71%] vs. 0 [0%], P < 0.001). The only significant difference in baseline characteristics was history of non-initial procedure. While 86% of group B patients had a previous non-initial procedure, only 53% of group A patients underwent previous replacement (P < 0.05). In multivariate analysis, previous non-initial procedure was the only predictor for need of extraction at 1 year, hazard ratio 3.5, 95% confidence interval 1.001–11.73, P < 0.05.

Conclusions: Conservative treatment in patients with EPII after non-initial procedure can lead to serious adverse events resulting in the need for extraction. Close follow-up and aggressive treatment should be considered early in the therapeutic course.

Background: A cardiac restrictive filling patterns are associated with unfavorable prognoses. Cardiac interventions may change the natural history of patients.

Objectives: To investigate the prevalence of restrictive filling pattern in routine echocardiographic examinations and their association with morbidity and mortality.

Methods: The clinical and echocardiographic data of patients with newly diagnosed restrictive filling pattern were analyzed and summarized.

Results: Among 8000 patients who underwent an echocardiographic examination in our hospital in 2013, a restrictive filling pattern was identified in 256. Of these, 134 showed a restrictive filling pattern that was newly diagnosed. Mean age was 69 years. Hypertension, diabetes, and ischemic heart disease were found in 81%, 60%, and 53%, respectively. Left ventricular ejection fraction was 42% ± 16%. Severe valvular abnormalities were found in 18%. During follow-up (29 ± 15 months), 40% of patients died. The strongest predictor of mortality (73%) was moderate or more advanced aortic stenosis, P = 0.005. Renal failure was an important independent predictor of mortality (53%, P < 0.05). A very high E/E' ratio ≥ 20, was another independent mortality predictor (50%, P < 0.03). Patients who died were less likely to have undergone cardiac interventions than those who survived (26% vs. 45%, P < 0.03).

Conclusions: Prevalence of restrictive filling among echocardiographic studies is 3.2%. In a half of these, the restrictive filling pattern is a new diagnosis. Patients who are diagnosed with a new restrictive filling pattern have higher mortality rates. Patients with restrictive filling should be evaluated thoroughly for possible coronary artery or valvular heart disease.

Background: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan.

Objectives: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage.

Methods: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses.

Results: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20.

Conclusions: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.

Background: Mortality and decrease in function after hip fracture are significantly related to patient factors including age, gender, co-morbidities, and mental status. Several studies demonstrated ethnic disparities in incidence, mortality, and functional outcome after hip fractures in the United States.

Objectives: To assess the relationship between ethnicity and hip fracture incidence and outcomes of mortality, functional change, and perioperative complications in the Israeli population.

Methods: We reviewed our institutional hip fracture registry for all patients from 2014–2015. Patients with incomplete data, < 60 years of age, or pathologic and periprosthetic fractures were excluded. Our study comprised 693 patients. Ethnicity was based on country of birth. Specifically, for those born in Israel, the nationality of either Jewish or Arab was further dichotomized. Perioperative complications, mortality, and mobility status at 1 year follow-up were recorded. The ethnicities of 27,130 patients admitted to the medicine and surgical wards during the same time interval served as a control group for the hip fracture cohort.

Results: Immigrants from Europe and America had the highest incidence of hip fractures. Fracture types varied in incidence in groups with 70% of extracapsular hip fractures occurring in Arabs and immigrants from Eastern countries, compared to 60% in immigrants from Western countries and the former Soviet Union. Mortality, perioperative complications, and mobility at 1 year were similar in all ethnic groups.

Conclusion: Our study demonstrated significant differences in incidence and fracture characteristic among ethnicities, but no difference in patient outcome. These findings differed from the available North American studies.

Background: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized.

Objectives: To describe a familial association with IIH.

Methods: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013.

Results: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25–35 kg/m²), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH.

Conclusions: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.