Israel Medical Association Journal

Background: A dental appliance for obstructive sleep apnea (OSA) is recommended for patients who cannot adjust to continuous positive airway pressure (CPAP) treatments.



Objectives: To describe patients with extremely severe OSA who were successfully treated with a dental appliance and to compare their characteristics with the relevant literature to identify clinical features associated with a good outcome.



Methods: The clinical, management, and outcome data of three patients with an apnea-hypopnea index (AHI) of > 80 who showed clinical improvement following treatment with a dental appliance were collected retrospectively from sleep laboratory reports in Israel over a period of 3 years. 



Results: The patients included one man and two women, aged 33, 56, and 61 years, respectively. The diagnosis of OSA was based on clinical examination and polysomnography. AHI values at presentation were 83, 81, and 84, respectively. Treatment with a dental appliance (Herbst® or MDSA®) was proposed due to patient noncompliance with CPAP. Follow-up polysomnography with the dental appliance revealed a reduction in the AHI to 1.7, 10.7, and 11, respectively. All patients had supine OSA and a retrognathic mandible, both of which have been found to be associated with a good prognosis for treatment with a dental appliance.



Conclusions: Dental appliances may be considered an appropriate second-choice option to treat severe OSA in patients who are noncompliant with CPAP. This study helps physicians identify patients with extremely severe OSA who are suitable for dental appliance treatment. Well-designed large-scale studies are needed to reach definitive conclusions. 

Background: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF.

Objectives: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program.

Methods: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later.

Results: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3).

Conclusions: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

Background: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation.

Objectives: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel.

Methods: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study.

Results: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%.

Conclusions: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

Background: Management of postoperative pain has become a growing concern, even for minor gynecological procedures. Proper postoperative pain management has been shown to lead to earlier mobilization, shortened hospital stay, and increased patient satisfaction. The optimal means of reducing the pain of pregnancy termination has not yet been determined.

Objectives: To compare the efficiency in pain management of two drugs, lornoxicam and paracetamol, given intravenously postoperatively to women who underwent abortion with dilation and curettage. 

Methods: The cohort comprised 80 women scheduled for dilation and curettage for pregnancy termination at 6–12 gestational weeks. The anesthesiologist gave 1000 mg paracetamol or 20 mg lornoxicam soon after starting the procedure, according to a randomization table. The medical staff and the patients were blinded to the drug that was administered. Pain levels were evaluated by a 10 cm visual analogue scale (VAS) at 15, 30, 60, 90, and 120 minutes following arrival at the postoperative care unit. 

Results: Mean levels of pain decreased from 60 minutes postoperative until the end of recording, reaching minimum levels at 120 minutes: 0.8 ± 0.19 and 1.5 ± 0.28, for lornoxicam and paracetamol, respectively. The differences between the groups were statistically significant (P < 0.05 from 60 minutes after the procedure until the time of discharge. 

Conclusions: Compared to women who received paracetamol, women who received lornoxicam after dilation and curettage for termination of pregnancy reported lower levels of pain, from 30 minutes postoperative until the time of discharge following the procedure. 

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

A fundamental challenge for multiple sclerosis (MS) therapy is to promote repair and remyelination beyond their limited spontaneous extent. Glatiramer acetate (GA, Copaxone®), an approved treatment for MS, has been shown to induce immunomodulation as well as neuroprotection in the inflamed central nervous system (CNS) in MS and in its model, experimental autoimmune encephalomyelitis (EAE). Using electron microscopy, immunohistochemistry, and advanced magnetic resonance imaging, we have demonstrated diminished myelin damage in GA-treated mice, in both relapsing-remitting and chronic EAE, even when treatment was applied late after the disease exacerbation, suggesting repair. Furthermore, quantitative analysis indicated significant elevation in remyelinated axons in GA-treated compared to untreated EAE mice. To further prove that GA can promote myelination, we studied its effect in the developing naïve CNS, when injected postnatally. Immunohistochemical and ultrastructural analyses revealed significant increase in the number of myelinated axons, the thickness of the myelin encircling them, and the resulting g-ratios in the spinal cords of GA-injected mice compared to their phosphate-buffered saline-injected littermates. A prominent elevation in the amount of progenitor oligodendrocytes and their proliferation, as well as in mature oligodendrocytes, implied that the effect of GA is linked to the differentiation along the oligodendroglial cascade. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates. These cumulative findings indicate that GA treatment affects myelination under inflammatory as well as non-inflammatory conditions, supporting the notion that the repair process in the CNS can be up-regulated by therapy.

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Background: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival.

Objectives: To report the outcomes of patients after aortic valve replacement with the Freestyle® stentless bioprosthesis in the Tel Aviv Medical Center followed for ≤ 15 years.

Methods and Results: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 ± 9.2 years, 4.2 ± 1.5 and 10.2 ± 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 ± 29.1 vs. 22.8 ± 9.6 mmHg, P < 0.0001; and 43.4 ± 17.2 vs. 12.1 ± 5.4 mmHg, P < 0.0001 respectively) in 3 months of follow-up. Mean overall follow-up was 4.9 ± 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 ± 2.5% and 57.2 ± 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 ± 2.3% vs. 76.0 ± 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 ± 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one.

Conclusions: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients. 

Pulmonary epithelioid hemangioendothelioma (PEH), previously known as "intravascular bronchoalveolar tumor," is a rare vascular malignancy with an unpredictable prognosis. Treatment can vary from observation in asymptomatic patients to surgery in patients with resectable disease or chemotherapy in patients with disseminated disease. This report describes the clinical, radiological and pathological features of three cases of PEH and a review of the current literature.