Israel Medical Association Journal

Background: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE).

Objectives: To conduct the first nationwide survey focused on BrS patients with documented AE.

Methods: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2).

Results: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13–84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30–53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine.

Conclusions: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Background: Erysipelas, an acute infection of the dermal and subcutaneous tissue, is normally treated with antibiotics. Previous data indicated that treatment with prednisone in combination with antibiotics results in significant acceleration of the healing phase.

Objectives: To investigate the effectiveness of corticosteroids combined with antibiotics for the treatment of erysipelas.

Methods: A retrospective study was conducted on hospitalized patients diagnosed with erysipelas between 2004 and 2011 at the Department of Dermatology at Sheba Medical Center, Israel. Data included epidemiology, medical background, and course of the disease as documented at admission and during hospitalization. 

Results: Data were collected on 173 patients (66% males) who were divided into two groups: a control group treated with antibiotics only (97 patients) and a study group treated with antibiotics and prednisone (76 patients). The study group presented with a more severe form of erysipelas (bullous) and those patients were hospitalized for a longer period (8.5 vs. 7 days). Nevertheless, the study group exhibited a 71% clinical improvement shortly after being treated with prednisone, without significant side effects. Short-term follow-up revealed more edema in the study group; however, long-term follow-up revealed a higher incidence of erythema and recurrence of erysipelas in the control group. The return to full function was faster in the study group than in the control group. 

Conclusions: Combining prednisone with antibiotics for the treatment of erysipelas should be considered, especially in severe cases. In addition, a prospective double-blind study should be conducted to verify these conclusions.

Background: Controlled ovarian hyperstimulation (COH) followed by oocyte retrieval is a leading option for fertility preservation before chemotherapy, yet this procedure causes excessive serum levels of estradiol (E2), which are often detrimental for cancer patients. Aromatase inhibitors are often used in breast cancer patients during COH to prevent elevated levels of E2.

Objectives: To describe our experience with COH for oocyte cryopreservation in non-breast cancer patients using aromatase inhibitors.

Methods: Of the five patients treated, two had an aggressive abdominal desmoid tumor, one had endometrial carcinoma, one had uterine sarcoma, and one patient had a brain oligodendroglioma. In all cases the treating oncologist suggested an association between estrogen and possible tumor progression. All patients were treated with a standard in vitro fertilization antagonist protocol combined with aromatase inhibitors, similar to the protocol used for breast cancer patients.

Results: The average duration of treatment was 10.5 days, mean peak E2 was 2348 pmol/L, mean number of oocytes aspirated was 17.3, and a mean of 14.6 embryos/oocytes were cryopreserved.

Conclusions: COH with aromatase inhibitors is apparently effective in non-breast cancer patients and spares exposure to high E2 levels.

Background: Sonographic assessment of the fetal kidneys is an integral part of the prenatal anatomical survey.

Objectives: To evaluate the fetal renal to abdominal (RTA) ratio throughout pregnancy and to investigate whether this ratio can be a potential diagnostic landmark for congenital anomalies of the kidney and urinary tract (CAKUT).

Methods: Measurements of the anterior-posterior diameters of the fetal kidney and fetal abdomen (APAD) were obtained prospectively. The RTA was calculated as the ratio between them in in two groups: normal population vs. CAKUT cases. RTA in CAKUT cases was compared to RTA in a normal population.

Results: The study group was comprised of 210 women. The mean gestational age for the fetuses was 31 ± 5.6 weeks (range 14–40 weeks). Fetal RTA ratio was found to be 0.28 ± 0.03 throughout pregnancy from early second trimester to term, with high reproducibility of measurements. During the study period the RTA was evaluated in nine cases referred for suspected CAKUT. All cases demonstrated a different ratio according to the renal anomaly. High ratio was observed in one case of overgrowth syndrome (Beckwith Wiedenmann syndrome; 0.47), three cases of infantile polycystic kidney (0.45–0.47), and three cases of a solitary kidney (0.31–0.35), while cases of dysplastic kidneys revealed a low ratio (0.14–0.18).

Conclusions: Prenatal RTA ratio is constant throughout gestation. An abnormal ratio should lead to meticulous renal investigation to rule out kidney disease.

Background: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate.

Objectives: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC.

Methods: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher’s exact tests.

Results: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001).

Conclusions: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment.

Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions.

Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied.

Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity.

Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.

Background: Since the introduction of the electrocardiogram (ECG) in 1902, the fundamentals of ECG data acquisition, display, and interpretation in the clinical arena have not changed much.

Objectives: To present a new method to enhance and improve acquisition, analysis, and display of the standard ECG.

Methods: We performed ECG enhancement by superimposition and summation of multiple standard ECG cycles of each lead, by temporal alignment to peak R wave and voltage alignment to an improved baseline, at the T-P segment.

Results: We enhanced ECG recordings of 504 patients who underwent coronary angiograms for routine indications. Several new ECG features were noted on the enhanced recordings. Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to the discovery of a new observation, which may help to distinguish between patients with and without coronary artery disease (CAD): namely, a spontaneous cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T-P interval. The mean normalized VS was significantly greater in those with CAD (n=61, 40%) than without (n=91, 60%), 5.61 ± 3.79 vs. 4.01 ± 2.1 (P < 0.05).

Conclusions: Our novel method of multiple ECG-cycle superimposition enhances the ECG display and improves detection of subtle electrical abnormalities, thus facilitating the standard rest ECG diagnostic power. We describe, for the first time, voltage spread at the S-T interval, an observed phenomenon that can help detect CAD among individuals with normal rest 12-lead ECG.

Background: Multiform fascicular tachycardia (FT) was recently described as a ventricular tachycardia (VT) that has a reentrant mechanism using multiple fascicular branches and produces alternate fascicular VT forms. Ablating the respective fascicle may cause a change in the reentrant circuit resulting in a change in morphology. Ablation of the septal fascicle is crucial for successful treatment.

Objectives: To describe four cases of FT in which ablation induced a change in QRS morphologies and aggravated clinical course.

Methods: Four out of 57 consecutive FT cases at three institutions were retrospectively analyzed and found to involve multiform FT. These cases underwent electrophysiological study, fascicular potential mapping, and electroanatomical mapping. All patients initially had FT with right bundle branch block (RBBB) and superior axis morphology.

Results: Radiofrequency catheter ablation (RFCA) targeting the distal left posterior fascicle (LPF) resulted in a second VT with an RBBB-inferior axis morphology that sometimes became faster and/or incessant and/or verapamil-refractory in characteristics. RFCA in the upper septum abolished the second VT with no complications and uneventful long-term follow-up.

Conclusions: The change in FT morphology during ablation may be associated with a change in clinical course when shifting from one route to another and may aggravate symptoms. Targeting of the proximal conduction system (such as bifurcation, LPF, left anterior fascicle, high septal/auxiliary pathway) may serve to solve this problem.

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm³. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

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: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%–5% have severe sight-threatening disease due to optic neuropathy Optical coherence tomography (OCT), the non-invasive imaging technology that yields high-resolution cross-sectional images of the retina, provides qualitative and quantitative data on the retina.

Objectives: To apply this technique to quantitatively assess retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects and in patients with TAO to determine their relationship to the severity of the orbital disease.

Methods: All patients in the ophthalmology clinic who were diagnosed with TAO and underwent OCT imaging as part of their ocular examination comprised the study group, and healthy patients who volunteered to undergo OCT examination served as controls. Results of the complete ophthalmologic examination and OCT findings were collected from medical files, including the thickness of the RNFL and the macula.

Results: The study comprised 21 patients and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula thinning compared to healthy subjects. Mean RNFL thickness was correlated with the severity of the orbital disease.

Conclusion: The OCT findings suggest that the retina is involved in TAO, probably as early as the subclinical stage. This highlights the ability of OCT to identify retinal changes earlier and far more accurately than is detected today, enabling earlier diagnosis and more timely treatment to prevent severe visual sequelae.

Background: In recent years, the role of intrapartum sonography has expanded in childbirth management, in subjective clinical situations such as arrested deliveries, or prior to instrumental deliveries.

Objectives: To assess the current use of intrapartum ultrasound by obstetricians in Israel.

Methods: An anonymous questionnaire was completed by 79 obstetricians in second- and third level- hospitals in Israel. The results were analyzed according to main subspecialty (sonography, delivery), experience and gender.

Results: A questionnaire was completed by 56 senior obstetricians and 23 interns with an average experience of 14.3 and 2.4 years, respectively. All obstetricians performed ultrasound examinations in the delivery room for basic indications such as fetal presentation during twin delivery and to rule out placenta previa. Sonographers consistently reported advanced indications as compared to senior members of delivery teams and interns in the assessment of prolonged first (52% vs. 14% vs. 14%) and second stage of labor (88% vs. 52% vs. 62%) and in assessment of fetal head station (60% vs. 30% vs. 22%), head progression during descent (48% vs. 23% vs. 11%), diagnosis of head position (88% vs. 68% vs. 60%), spine direction (92% vs. 59% vs. 53%) and asynclytism (41% vs. 20% vs. 29%).

Conclusions: Ultrasound is currently used by all physicians in the delivery room for basic indications. However, obstetric teams report a low use of advanced intrapartum ultrasound and prefer to rely on their clinical experience. Advanced intrapartum sonographic imaging should be an integral part of obstetric qualifications. A steep learning curve, along with high reproducibility, suggests that ultrasound devices will become a common tool in labor and delivery management.