Israel Medical Association Journal

Background: Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases.

Objectives: To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts.

Methods: We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities.

Results: The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings.

Conclusions: To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.

Background: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting.

Objectives: To examine the change in corneal and conjunctival sensation post-pterygium surgery.

Methods: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively.

Results: Nine patients participated in the study. Mean follow-up time was 9 months (9 ± 3.3, 6–12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation).

Conclusions: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

Background: Keratoconus is a non-inflammatory disease characterized by progressive corneal steepening, which leads to decreased visual acuity secondary to high irregular astigmatism.

Objectives: To compare the one-year outcomes of accelerated vs. standard collagen crosslinking (CXL) in the treatment of keratoconus.

Methods: A database search of patients who underwent CXL from 2009 to 2017 was conducted at the cornea clinic at Sheba Medical Center. Charts of 99 adult patients (124 eyes) were reviewed. All patients were diagnosed with keratoconus. Main outcome measures were change in keratometry, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA).

Results: We evaluated outcomes in two groups: CXL with standard (3 mW/cm² for 30 minutes) vs. the accelerated (9 mW/cm² for 10 minutes) protocol. There were no significant differences between the groups with regard to BCVA, UCVA, and mean spherical equivalent (P =0.83, 0.0519, 0.181, respectively). The corneal thickness in the center and thinnest location were higher in the accelerated group than the in the standard group (P = 0.126). Complication rates did not differ between the two groups.

Conclusions: Accelerated and standard CXL are both safe and effective techniques. Accelerated CXL confers the added benefit of being a faster procedure to both patients and surgeons.

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: Accurate assessment of liver fibrosis is crucial for the management of patients with hepatitis C virus (HCV) infection.

Objectives: To evaluate the performance of liver segment-to-spleen volume ratio in predicting the severity of liver fibrosis.

Methods: Sixty-four consecutive HCV patients were enrolled in this retrospective study. All patients underwent contrast-enhanced computed tomography (CT) and were divided into three groups based on their hepatic fibrosis stage evaluated by shear-wave elastography (SWE): non-advanced (F0–F1, n=29), advanced (F2, n=19) and severe fibrosis (F3–F4, n=16). Using semi-automated liver segmentation software, we calculated the following liver segments and spleen volumes for each participant: total liver volume (TLV), caudate lobe (CV), left lateral segment (LLV), left medial segment (LMV), right lobe (RV) and spleen (SV), a well as their ratios: CV/SV, RV/SV, LLV/SV, LMV/SV and TLV/SV.

Results: RV/SV was found to discriminate between patients with non-advanced and advanced fibrosis (P = 0.001), whereas SV, CV, RV, TLV/SV, LMV/SV and RV/SV discriminated between patients with advanced and severe fibrosis (P < 0.05). RV/SV ≤ 3.6 and RV ≤ 2.9 were identified as the best cutoff values to differentiate non-advanced from advanced fibrosis and advanced from severe fibrosis with sensitivities of 72.2% and 92.7%, specificities of 72.7% and 77.8%, and with an area under the receiver operating characteristic (ROC) curve of 0.797 and 0.847, respectively (P ≤ 0.002).

Conclusions: RV/SV may be used for the assessment and monitoring of liver fibrosis in HCV patients prior to the administration of antiviral therapy, considering SWE as the reference method.

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: Kikuchi-Fujimoto disease is a benign and self-limited disease, first reported in Japan in 1972. The characteristic features of this disorder include lymphadenopathy and fever.

Objectives: To summarize our experience with Kikuchi disease with regard to clinical manifestations and outcome.

Methods: The patients included in the study were those diagnosed with Kikuchi disease during the years 2005–2008 in two departments of internal medicine at Sheba Medical Center.

Results: We identified five patients with Kikuchi disease; four of them were women and the mean age was 22.6 years. All the patients had cervical lymphadenopathy; three had other sites of lymphadenopathy. Four of the patients had fever higher than 39ºC. Two of them had splenomegaly and three reported weight loss. Three of the five patients experienced a relapse of the disease and were treated with steroids or non-steroidal anti-inflammatory agents. The diagnosis was confirmed in all the patients by an excisional biopsy of lymph node.

Conclusions: Kikuchi disease must be considered in every young patient with fever and lymphadenopathy. The disease usually has a benign course.

Background: A survey conducted among Israel Defense Force primary care physicians in 2001 revealed that they consider patients' needs more than they do organizational needs and that the education PCPs[1] currently receive is inadequate. In 2003 the medical corps initiated a multi-format continuous medical education program aimed at improving skills in primary care medicine.

Objectives: To measure and analyze the effect of the tailored-made CME[2] program on PCPs’ self-perception 3 years after its implementation and correlate it to clinical performance.

Methods: In 2006 a questionnaire was delivered to a representative sample of PCPs in the IDF[3]. The questionnaire included items on demographic and professional background, statements on self-perception issues, and ranking of roles. We compared the follow-up survey (2006) to the results of the original study (2001) and correlated the survey results with clinical performance as measured through objective indicators.

Results: In the 2006 follow-up survey PCPs scored higher on questions dealing with their perception of themselves as case managers (3.8 compared to 4.0 on the 2001 survey on a 5 point scale, P = 0.046), perceived quality of care and education (3.5 vs. 3.8, P = 0.06), and on questions dealing with organizational commitment (3.5 vs. 3.8, P=0.01). PCPs received higher scores on clinical indicators in the later study (odds ratio 2.05, P < 0.001).

Conclusions: PCPs in the IDF perceive themselves more as case managers as compared to the 2001 survey. A tailor-made CME program may have contributed to the improvement in skills and quality of care.

Background: Research on synergistic effects of patient-targeted interventions combined with physician-targeted interventions has been limited.

Objectives: To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.

Methods: In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure; the proportion of patients with HbA1c[1] < 9%, LDL[2] < 130 mg/dl and SBP[3] < 140 mmHg both as separate outcomes and combined.

Results: After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c < 9%, LDL < 130 mg/dl and SBP < 140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).

Conclusions: Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease. 

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Objectives: To determine whether this policy is still applicable. 

Methods: We performed prospective sampling and follow-up of women admitted for labor and delivery between February 2002 and July 2002. Vaginal and rectal cultures were obtained before the first pelvic examination. GBS isolation was performed using selective broth medium, and identified by latex agglutination and serotyping. Demographic data were collected by means of a standardized questionnaire. Data on the newborns were collected throughout 2002.

Results: Of the 629 sampled women, 86 had a positive culture and a carrier rate of 13.7%. A borderline significantly higher carriage rate was observed among mothers of North American origin (21% vs. 13.1%, P = 0.048), and a higher attack rate in their infants (3.8/1000 compared with 0.5/1000 live births in our general maternal population, P = 0.002). Eight newborns had early-onset neonatal GBS sepsis (a rate of 0.8/1000 live births), but none of them benefited from intrapartum antibiotic prophylaxis.

Conclusions: An increased neonatal disease rate was observed in a population with a higher colonization rate than previously seen. In lieu of the higher carrier rates, we now recommend routine prenatal screening for GBS in our perinatal population.