Israel Medical Association Journal

Background: The continuity equation (CE) used for evaluating aortic stenosis (AS) is based on values obtained from transthoracic echocardiography (TTE) with the assumption that the left ventricular outflow tract (LVOT) has a circular shape. Transesophageal echocardiography (TEE) may be used for accurate measurement of the LVOT cross-sectional area (CSA). Previous studies have focused on fusion from TEE for LVOT-CSA measurement and TTE for velocity time integrals (VTI) calculations.

Objectives: To assess aortic valve area (AVA) using parameters obtained exclusively from TEE as an alternative approach.

Methods: Thirty patients with equivocal AS based on TTE were evaluated using TEE for further assessment.

Results: The mean pressure gradient across the aortic valve (AV) was 38 ± 5.9 and 37.9 ± 7.6 mmHg in TTE and TEE, respectively, P = 0.42. LVOT-CSA was larger in TEE (3.6 ± 0.3 vs. 3.4 ± 0.3 cm², P = 0.049). VTI over the AVA was similar (98.54 ± 22.8 and 99.52 ± 24.52 cm in TTE and TEE, respectively, P = 0.608), while VTI across the LVOT was higher when measured by TTE (24.06 ± 5.8 vs. 22.03 ± 4.3 cm, P < 0.009). Using the CE, AVA was 0.82 ± 0.3 vs. 0.83 ± 0.17 cm² in TEE vs. TTE, respectively, P = 0.608. Definitive grading was achieved in all patients (26 patients defined with severe AS and 4 with moderate).

Conclusions: In equivocal cases of AS, full assessment using TEE may be a reliable modality for decision making.

Carbamoyl phosphate synthetase 1 (CPS1; MIM *608307; E.C. 6.3.4.16) is the first rate-limiting enzyme of the urea cycle, an essential metabolic pathway for ammonia detoxification. CPS1 deficiency (CPS1-D) is characterized by severe hyperammonemia during disease exacerbations. During a metabolic crisis, children with CPS1-D are admitted with vomiting, altered mental status, and high serum levels of ammonia. Rapid normalization of ammonia level ameliorates neurological outcome [1,2]. The first-line treatment for hyperammonemia in these patients is ammonia scavengers in combination with citrulline or arginine and high-calorie supplementation while controlling protein intake [1].

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].

Background: Serasis® (Serag-Wiessner KG, Naila, Germany) is a light-weight mid-urethral sling for treating stress urinary incontinence (SUI). Its insertion is considered less traumatic than other mid-urethral slings.

Objectives: To define postoperative outcomes following Serasis implantation. To compare the efficacy and complication rates of the implant to those of other common techniques.

Methods: Our retrospective study evaluated patients who underwent Serasis mid-urethral sling surgery for SUI. Data were collected from medical records prior to and at the time of surgery and by telephonic interview for postoperative pain and complications. Follow-up of patients was performed for up to one year postoperatively. Patients rated pain or discomfort according to the Visual Analogue Scale (VAS). The primary outcome was the development of early postoperative pain during the first month after surgery. Secondary outcomes were relief of SUI symptoms, groin pain or discomfort, and other postoperative complications up to 12 months after surgery.

Results: The study cohort included 50 consecutive patients aged 31 to 68 years. All patients underwent Serasis implantation procedures by a single surgeon and completed interviews. In total, 35 patients underwent concomitant anterior colporrhaphy. In the immediate postoperative period and at one month after the procedure, complaints were mild. No complaints were recorded during the 12-month follow-up period. Overall, 90% and 92% of the patients were free of SUI symptoms at one month and 12 months after surgery, respectively.

Conclusions: Serasis mid-urethral sling is safe, effective, and associated with mild postoperative pain and a low incidence of complications.

Background: Diagnosing occult stress urinary incontinence (OSUI) prior to surgical intervention for pelvic organ prolapse (POP) repair may allow for adding an anti-incontinence procedure and thus prevent postoperative SUI.

Objectives: To compare preoperative detection rates for OSUI by either a multichannel urodynamic investigation or by a plain pelvic examination.

Methods: We retrospectively evaluated the medical charts of all women who underwent urodynamic investigation prior to surgical repair of advanced POP at our institution between 1 January 2006 and 31 December 2012.

Results: In total, 720 women underwent surgical POP repair during the study period, of whom 54 (7.5%) were diagnosed with OSUI preoperatively. Of these patients, 54 (100%) were detected by multichannel urodynamic investigation while only 27 (50%) were detected by a plain pelvic examination (P = 0.001). Bladder fullness during the pelvic examination was associated with higher detection rates for OSUI (P = 0.001). Women with OSUI who underwent concomitant tension-free vaginal tape and POP repair procedures did not develop de novo SUI or obstructive voiding symptoms (OVS) postoperatively.

Conclusions: Preoperative multichannel urodynamic investigation has significantly higher detection rates for OSUI than a plain pelvic examination. Utilizing this modality resulted in no cases of de novo SUI or OVS postoperatively.

Stress urinary incontinence (SUI), defined as involuntary leakage of urine associated with increased intra-abdominal pressure during an effort such as sneezing or coughing, is a highly prevalent condition that affects women of all ages and impacts a women's quality of life (QoL). The prevalence of SUI reaches 14% in younger women and up to 35% in older women. Vaginal deliveries, gravidity, advanced age, menopause status, obesity, diabetes, and ethnicity are known risk factors for SUI [1].

The prevalence of pelvic organ prolapse (POP) varies greatly and is reported to be between 3% and 50% differing greatly when based on POP symptoms or vaginal examination [1]. Age is a well-established risk factor in the reported prevalence of POP [2]. With advancing age, the prevalence escalates dramatically, from 6% at age of 30 years to over 50% at the age of 80 years [3]. The increase in life expectancy observed in recent years will most probably be accompanied by a respective increase in the absolute numbers of women presenting with POP [4]. POP is a major health burden and is expected to continue being so in the upcoming future; hence, the importance of a safe and efficient treatment.

Background: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown.

Objectives: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status.

Methods: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician–patient agreement was assessed by intraclass correlation coefficient.

Results: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician’s evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician–patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders.

Conclusions: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician

Background: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time.

Objectives: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients.

Methods: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0–3). The total inflammatory score was the sum of the scores.

Results: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P  = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01).

Conclusions: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset

Background: Belimumab was the first biological drug approved for the treatment of systemic lupus erythematosus (SLE) patients. Phase II/III randomized controlled trials and real-life studies identified patients with musculoskeletal involvement as best responders.

Objective: To evaluate the effectiveness of belimumab in SLE-related joint involvement.

Methods: The cohort comprised SLE patients receiving belimumab for musculoskeletal indications. Belimumab was intravenously administrated according to protocols; all the patients were evaluated at baseline (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. We assessed joint activity by disease activity score 28, simple disease activity index (SDAI), clinical disease activity index (CDAI), and swollen tender ratio. Each patient underwent musculoskeletal ultrasound of 34 joints to assess synovial effusion synovial hypertrophy, and power Doppler; by using a semi-quantitative scale (0–3) we obtained the total inflammatory score (0–216).

Results: We evaluated 20 patients (males/females 1/19, median age 45 years [interquartile range (IQR) 12], median disease duration 144 months [IQR 144]). CDAI and SDAI significantly decreased at T1 (P = 0.02 and P = 0.01 respectively) and this improvement was maintained at the following time-points (CDAI: T2 P = 0.008, T3 P = 0.004; SDAI: T2 P = 0.006, T3 P = 0.01). A significant reduction of median ultrasound score was identified at T1 (T0 20.5 [IQR 13.5] vs. T1 7.5 [IQR 4.7], P < 0.001), and maintained at T2 (7.0 [IQR 5], P < 0.0001), and T3 (7.0 [IQR 9.0], P < 0.0001).

Conclusions: Belimumab induces a sustained improvement of ultrasound-detected inflammatory status at the articular level.

Background: Cyclophosphamide treatment has been associated with ovarian function impairment. Co-treatment with gonadotropin-releasing hormone-analogue (GnRH-a) seems to be able to prevent this complication. However, even though data are available on neoplastic patients, limited data have been published on systemic lupus erythematosus (SLE) women cohorts

Objectives: To evaluate GnRH-a efficacy on ovarian function preservation in SLE women receiving cyclophosphamide treatment

Methods: The authors performed a retrospective study including SLE women requiring cyclophosphamide treatment and compared those treated with and without GnRH-a (case and controls, respectively). All patients were evaluated before cyclophosphamide treatment and every 3 months in the following years. Ovarian function was evaluated using hormonal profiles

Results: The study comprised 33 SLE cyclophosphamide-treated women: 18 co-treated with triptorelin and 15 controls. The mean follow-up was 8.1 ± 5.1 years (range 4–11). Premature ovarian failure (POF) prevalence was significantly lower in SLE women treated by cyclophosphamide plus triptorelin compared to controls (11.1% vs. 33.3%, P = 0.0002). The occurrence of POF was significantly associated with higher age at the time of cyclophosphamide treatment (P = 0.008). Only patients in the GnRH-a treated group had successful pregnancies

Conclusions: The study provides information about the efficacy of co-treatment with GnRH-a in SLE women receiving cyclophosphamide, as demonstrated by the lower POF incidence compared to untreated subjects, based on long-term follow-up. These results reinforce the use of GnRH-a for fertility preservation in premenopausal SLE patients treated by cyclophosphamide

Recurrent pericarditis is a state of repetitive inflammation of the pericardium with intervals of remission. The etiology of recurrent pericarditis is still largely unknown, yet most causes are presumed to be immune mediated. Genetic factors, including human leukocyte antigen (HLA) haplotypes, can be involved in dysregulation of the immune system and as a predisposition to several autoimmune conditions, including recurrent pericarditis. Several diseases are frequently associated with such manifestations. They include systemic lupus erythematosus, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome. However, idiopathic recurrent pericarditis remains the most frequently observed clinical condition and the conundrum of this disease still needs to be solved.

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.