Israel Medical Association Journal

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: Right hydronephrosis secondary to acute appendicitis is an under-reported phenomenon with only several case reports published.

Objectives: To assess the incidence of this phenomenon in our database of patients diagnosed with acute appendicitis.

Methods: Data were collected on 1092 patients who underwent surgery due to acute appendicitis between 2003 and 2007 in our tertiary medical center. The data entailed demographic, surgical, and hospitalization parameters including ultrasound or computed tomography examinations and presence of right hydronephrosis prior to surgery.

Results: Out of 1092 patients, appendicitis was eventually diagnosed in 87.4% of the patients. Only 594 (54%) had preoperative imaging performed prior to surgery (ultrasound or computed tomography). Out of these 594 patients, 21 (3.5%) had a new right hydronephrosis diagnosed and all had appendicitis with 15/21 (71%) having a retrocecal appendix. Of those with retrocecal appendix, 10 were pregnant women (48%). Erythrocyturia was present in 15/21 patients (71%) and in 10/11 of patients (91%) after excluding those who were pregnant. No significant differences were seen in patients with hydronephrosis regarding age, hospitalization, and surgery time. In all patients, an ultrasound was performed 2 weeks after surgery demonstrating the disappearance of hydronephrosis. Median follow-up time was 41.7 months (range 14.8–118.4 months).

Conclusions: Our study shows that 3.5% of our cohort had right hydronephrosis secondary to acute appendicitis. Although this presentation is very rare, physicians should be aware of this phenomenon and the risk for delayed diagnosis and treatment of acute appendicitis.

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: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring.

Objectives: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission.

Methods: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO₂) from 100%.

Results: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO₂ values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO₂ values). Among hypoxemic patients (initial SpO₂ < 90%), protocol implementation had a greater impact on final SpO₂ measurements, increasing their median SpO₂ readings by 4% (3–8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO₂ potential.

Conclusions: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.

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: The estimated incidence of esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is 1:3500 live births. During childhood these patients have various co-morbidities, but the overall quality of life among adults is similar to that of the general population.

Objectives: To evaluate short- and long-term co-morbidities and quality of life among infants born with EA ± TEF at a large single medical center.

Methods: Medical records of 65 children born over a 21 year period were reviewed for short- and long-term medical data. Telephone interviews were conducted with 46 of their parents regarding medical problems and quality of life after home discharge.

Results: The main long-term co-morbidities during the first 2 years of life, 4–6 years of age, and during adolescence (12–16 years) included gastro-esophageal reflux disease (GERD) in 56.5%, 35.8%, and 18.7%, respectively; stridor in 84.8%, 45.2%, and 12.5%, respectively; hyper-reactive airway disease (HRAD) in 43.5%, 35.5%, and 36.5%, respectively; recurrent pneumonia in 43.5%, 32.3%, and 18.8%, respectively; and overall recurrent hospitalizations in 87%, 41.9%, and 25%, respectively. The quality of life was reportedly affected among 100%, 75%, and 33.3% respectively.

Conclusions: Long-term follow-up of patients with EA ± TEF indicates a high burden of co-morbidities during the first 6 years of life, with a gradual decrease in symptoms thereafter. Nevertheless, HRAD continued to impact the daily life of about one-third of the older adolescents, and GERD one-fifth. A long-term multidisciplinary follow-up should be conducted to prevent late onset complications that may affect the quality of life.

Background: Previous surveys demonstrated variations in the clinical practices relating to the treatment and screening of maternal thyroid dysfunction.

Objectives: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel.

Methods: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified.

Results: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions.

Conclusions: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Acute appendicitis (AA) is one of the most common indications for emergency abdominal surgery.

Objective: To assess the diagnostic and prognostic value of serum bilirubin and liver enzyme levels in the management of acute appendicitis.

Methods: Consecutive emergency department patients referred for a surgical consult for suspected AA were prospectively enrolled in the study. Data regarding demographic, clinical and laboratory results were recorded. Receiver operating characteristic (ROC) curve was performed for all evaluated parameters. Clinical and laboratory markers were evaluated for diagnostic accuracy and correlation to the clinical severity, histology reports, and length of hospital stay.

Results: The study was comprised of 100 consecutive patients. ROC curve analysis revealed white blood cell count, absolute neutrophils count (ANC), C-reactive protein, total-bilirubin and direct-bilirubin levels as significant factors for diagnosis of AA. The combination of serum bilirubin levels, alanine transaminase levels, and ANC yielded the highest area under the curve (0.898, 95% confidence interval 0.835–0.962, P<0.001) with a diagnostic accuracy of 86%. In addition, total and direct bilirubin levels significantly correlated with the severity of appendicitis as described in the operative and pathology reports (P < 0.01). Total and direct bilirubin also significantly correlated with the length of hospital stay (P < 0.01).

Conclusions: Serum bilirubin levels, alone or combined with other markers, may be considered as a clinical marker for AA correlating with disease existence, severity, and length of hospital stay. These findings support the routine use of serum bilirubin levels in the workup of patients with suspected AA.

Background: Coronary artery disease (CAD) has known risk factors. Individual risks related to specific ethnicities are complex and depend on genetic predisposition and lifestyle.

Objectives: To compare the nature and prevalence of risk factors in Arab and non-Arab ethnic patients with symptomatic obstructive CAD referred for coronary angiography.

Methods: CAD, defined as coronary angiography with a ≥ 50% narrowing in ≥ 1 vessel, was diagnosed in 1029 patients admitted to a medical center between April 2014 and October 2015. Patients were divided into two groups according to ethnic origin: Arab vs. non-Arab. Demographics, clinical presentation, and coronary risk profiles were compared.

Results: The diagnosis of CAD was made during ST-elevation myocardial infarction (STEMI) in 198 patients (19%) who arrived at the clinic, 620 (60%) with unstable angina/non-STEMI, and 211 (21%) with stable angina. Patients with symptomatic CAD and Arab ethnicity were 47% more prevalent than non-Arab patients presenting with CAD. The Arab patients were appoximately 5 years younger, 50% more likely to be active smokers, 25% more likely to be obese, and more likely to have a family history of CAD. Other coronary risk factors were similar between the two groups.

Conclusions: Smoking and obesity, which are potentially modifiable CAD risk factors, stood out as major risk factors, in addition to genetic disposition, among Arab and non-Arab patients with symptomatic CAD. Screening and educational interventions for smoking cessation, obesity control, and compliance to treatment of co-morbidities should be attempted in order to decrease CAD in the Arab population.

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in Caucasian adults. Most patients have good renal prognosis, but 30–40% may progress to end stage renal disease (ESRD). 

Objectives: To evaluate the efficacy and safety of immunosuppressive treatment (IST) in high-risk patients.

Methods: All IMN patients diagnosed by kidney biopsy from 2004–2010 were included. Clinical and laboratory data were collected at each follow-up visit. Risk assessment for renal progression classified patients as high risk if: 24 hour protein excretion > 6 g/day, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and severe disabling or life-threatening clinical symptoms of NS were present.

Results: Among 290 biopsies, 37 patients (12.7%) were IMN. They were allocated to the high-risk IST group (n=16) or low-risk supportive treatment (ST) group (n=21) according to the likelihood of developing renal failure. Mean follow-up was 47 ± 17.3 months. Complete and partial remission rate was 68.7% for high-risk IST vs. 90.4% for low-risk ST. In the high-risk IST group, eGFR was significantly lower at 30 months (65.5 ± 28.6 vs. 85.3 ± 21.6 at baseline, P < 0.05). Four high-risk patients reached ESRD. In the low-risk ST group, eGFR remained stable at 30 and 60 months. 

Conclusions: This study showed a high remission rate for IMN. IST with prednisolone and cyclophosphamide provided favorable renal outcomes in most high-risk patients. The very high remission rate obtained in the low-risk patients confirms the adequacy of supportive treatment in this group.