Israel Medical Association Journal

Background: During military escalations emergency departments provide treatment both to victims of conflict-related injuries and to routine admissions. This requires special deployment by the hospitals to optimize utilization of resources.

Objectives: To evaluate “routine” visits to the ED[1] during Operation Cast Lead in Israel in 2008–2009.

Methods: We obtained data regarding routine visits to the ED at Soroka University Medical Center throughout OCL[2]. The visits one month before and after OCL and the corresponding periods one year previous served as controls.

Results: The mean number of daily visits throughout the study period (126 days) was 506 ± 80.9, which was significantly lower during OCL (443.5 ± 82) compared with the reference periods (P < 0.001). Compared to the reference periods, during OCL the relative rates were higher among Bedouins, visitors from the region closest to the Gaza Strip (< 30 km), patients transported to the ED by ambulance and patients of employment age; the rates were lower among children. No difference in the different periods was found in the rate of women patients, distance of residence from Beer Sheva, rate of patients referred to the ED by a community physician, and hour of arrival. The overall in-hospital admission rate increased during OCL, mainly in the internal medicine and the obstetric departments. There was no change in the number of in-hospital births during OCL; however, the rate of preterm labors (32–36 weeks) decreased by 41% (P = 0.013).

Conclusions: Throughout OCL the number of routine ED visits decreased significantly compared to the control periods. This finding could help to optimize the utilization of hospital resources during similar periods.

Background: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2–6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment.

Objectives: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980–2005).

Methods: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival.

Results: The patients’ mean age was 53 years (range 32–76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS[1]. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated by surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV.

Conclusions: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: Many patients in the internal medicine ward have anemia. The etiology for the anemia may be multifactorial and, in the setting of inflammatory process when the ferritin is increased, it is difficult to diagnose iron deficiency anemia. Soluble transferrin receptor (sTfR) had been suggested as an indicator for iron deficiency. No study has investigated the meaning of high sTfR as the only positive marker of iron deficiency anemia (IDA) caused by gastrointestinal tract (GIT) bleeding in hospitalized patients.

Objectives: To demonstrate the importance of high levels of sTfR as a marker for further GIT investigation in cases of anemia where the level of ferritin was normal or increased

Methods: We retrospectively assessed all patients in an internal medicine ward in our facility with anemia, high sTfR[1] levels (> 5.0 mg/L) and normal or high ferritin levels who underwent esophagogastroduodenoscopy and colonoscopy.

Results: Of 32 patients with anemia and normal or high ferritin levels and high sTfR, 22 patients (68%) had findings that explained IDA[2] (in some patients more than one finding). Those findings were colonic polyps (n=9), carcinoma of colon (n=4), duodenal ulcer (n=4), carcinoma of stomach (n=3), colitis (n=3), atrophic gastritis (n=1), erosive gastritis (n=1) and angiodysplasia (n=1).

Conclusions: High sTfR may be a good indicator of IDA caused by GIT[3] bleeding when the ferritin level is normal or high. GIT investigation is warranted in such cases.

Background: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar  cholangiocarcinoma  presents a complex surgical challenge.

Objectives: To assess the outcome of the radical approach for the management of types III and IV hilar  cholangiocarcinoma.

Methods: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepatico-jejunostomy.

Results: Fifteen patients (mean age 49 years, range 24–72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (R0) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6–72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively.

Conclusions: In selected patients, the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.
 

Primary biliary cirrhosis is considered a model autoimmune disease because of the similarities between patients, their relative homogeneous presentation and natural history, and the presence of the signature autoantibody, the anti-mitochondrial antibodies. PBC[1] also illustrates the potential role of genetic and environmental influence and is unique in having several well-defined animal models that recapitulate distinct features of the disease. The pathogenesis of the disease includes genetic predisposition, the production of both innate and adaptive immune responses, and cholangiocyte-specific biology that addresses the specificity of disease. In this review we highlight these features of PBC in comparison to other autoimmune diseases.

Background: The rate of brain abnormalities in asymptomatic term neonates varies substantially in previous studies. Some of these rates may justify general screening of healthy newborns by head ultrasound.

Objectives: To assess the incidence of intracranial abnormalities among asymptomatic term newborns with HUS[1] and to detect high-risk populations that might need such screening.

Methods: This was a prospective study in 493 term newborns who underwent HUS and a neurological evaluation during the first 3 days of life. The neurological examination results were unknown to the sonographist and the examiner was blinded to the HUS findings. The abnormal HUS findings were classified as significant or non-significant according to the current literature.

Results: Abnormal HUS was found in 11.2% of the neonates. Significant findings were noted in 3.8% of the infants. There was no association between non-structural HUS findings (hemorrhage or echogenicity) and mode of delivery. There was no relationship between any HUS abnormality and birth weight, head circumference and maternal age, ethnicity, education or morbidity. The rate of abnormal neurological, hearing or vision evaluation in infants with a significant abnormal HUS (5.2%) was comparable to the rate in infants with normal or non-significant findings on HUS (3.1%).

Conclusions: There is no indication for routine HUS screening in apparently healthy term neonates due to the relatively low incidence of significant brain abnormalities in these infants in our population.

Background: Overlap syndrome is an entity that satisfies the criteria of at least two connective tissue diseases. These conditions include systemic sclerosis, dermatomyositis or polymyositis, Sjogren's syndrome, rheumatoid arthritis and systemic lupus erythematosus. A combined pathology has impact on the clinical features, diagnosis and treatment.

Objectives: To analyze the features of SSc[1] patients with overlap syndrome registered in the European (EUSTAR) database at our center and to review the literature focusing on clinical and diagnostic issues and new treatments.

Methods: We studied the medical records of 165 consecutive SSc patients and reviewed cases with scleroderma overlap syndrome. Using the key words “overlap syndrome," "systemic sclerosis," “connective tissue disease” and “biological agents” we conducted a PubMed search for the period 1977 to 2009.

Results: Forty patients satisfied the criteria for scleroderma overlap syndrome. The incidence of additional connective tissue diseases in the whole group and in the overlap syndrome group respectively was: dermatomyositis or polymyositis 11.5% and 47.5%, Sjogren's syndrome 10.3% and 42.5%, rheumatoid arthritis 3.6% and 15.4%, and systemic lupus erythematosus 1.2% and 5.0%. Coexistence of SSc and another CTD[2] aggravated the clinical course, especially lung, kidney, digestive, vascular and articular involvement. Non-rheumatic complications mimicked SSc complications. An additional rheumatic or non-rheumatic disease affected treatment choice.

Conclusions: The definition of scleroderma overlap syndrome is important, especially in patients who need high-dose corticosteroids for complications of a CTD. The use of novel biological therapies may be advocated in these patients to avoid the hazardous influences of high-dose steroids, especially renal crisis. In some overlap syndrome cases, biological agents serve both conditions; in others one of the conditions may limit their use. In the absence of formal clinical trials in these patients a cautious approach is preferred.

Objectives: To assess our experience with perichondritis in a large group of patients hospitalized with this entity.

Methods: We retrospectively studied 114 patients who were admitted with perichondritis during 1987–2004, including their demographic details, medical history, current illness, etiology, pathogens and treatments. 

Results: The patients’ mean age was 41.8 ± 20.7 years. In more than half of the patients the etiology could not be determined. Forty-seven patients (41%) were treated prior to hospitalization for an average of 2.5 ± 1.9 days. Eight patients (7%) required surgical intervention. Pseudomonas aeruginosa was found to be the predominant organism (69% of available isolates) and was associated with a more advanced clinical presentation and longer hospitalization (P = 0.008). 

Conclusions:  Perichondritis develops in many cases after apparent minor trauma. Since P. aeruginosa is probably the predominant pathogen, initial treatment should include anti-pseudomonal antibiotics.

Background: Major advances in the treatment of perinatal asphyxial–hypoxic ischemic encephalopathy followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care.

Objectives: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE[1] in what we believe is the first report on non-experimental hypothermia for PA-HIE from Israel.

Methods: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008–2009.

Results: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5ºC) was begun at a median age of 4.2 hours of life (range 2.5–6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental follow-up of the five surviving infants at median age 7.2 months (4.1–18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures.

Conclusions: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: In infants, small volume nebulizers with a face mask are commonly used to facilitate aerosol therapy. However, infants may be disturbed by mask application, causing poor mask-to-face seal and thus reducing the dose delivered.

Objectives: To compare lung function response to bronchodilator nebulization via two delivery devices: hood versus mask.

Methods: We studied 26 recurrently wheezy infants aged 45.8 weeks (95% confidence interval 39.6–52.0). Inhalations of 0.30 mg/kg salbutamol were administered in two alliqots 30 minutes apart using mask and hood in alternating order (M+H or H+M). Response to inhalations was measured by maximal expiratory flows at functional residual capacity at 5 minute intervals after each dose, and area under the VmaxFRC[1] curve was documented.

Results: A small but significant response to salbutamol was observed following the second inhalation with VmaxFRC, improving by 31.7% (7.2–56.2, P < 0.02) and AUC[2] by 425 %•min (-154, 1004; P < 0.02). The improvement following salbutamol was similar by both delivery modalities but with a small but significantly better response when H was used after M (P < 0.01).

Conclusions: Nebulized salbutamol induced a variable but positive response in wheezy infants. Salbutamol via hood was as effective as conventional face mask delivery. Since it is simple and patient-friendly, it could replace the face mask method particularly with uncooperative infants.

Background: The term chronic multi-symptom illness refers to a spectrum of pain disorders, such as fibromyalgia and chronic fatigue syndrome, that are characterized by unexplained chronic pain, fatigue, and cognitive and mood complaints

Objectives: To examine the hypothesis that exercise cessation is associated with symptoms similar to CMI[1] in well-trained amateur athletes.

Methods: The study, conducted in running and triathlon clubs in Israel, involved 26 asymptomatic healthy athletes who regularly exercise 6.75 ± 3.65 hours a week. All athletes were instructed to refrain from physical activity for 7 days. All underwent a complete physical exam, rheumatological assessment including non-articular tenderness threshold (using dolorimeter) and tender points. In addition they completed the SF-36 quality of life questionnaire. Assessments were conducted before exercise cessation and 7 days later.

Results: Seven days after sports deprivation all subjects were significantly more tender by all tender measures (P < 0.001) (dolorimeter thresholds and tender point count). There was also a significant reduction in the scores for physical role function (P < 0.001), emotional role function (P < 0.001) and summary subscales of the SF-36 questionnaire after exercise cessation.

Conclusions: Exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. This may be associated with the development of chronic multi-symptom illness.