Israel Medical Association Journal

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that it is very difficult to diagnose in the early phase, resulting in a critical delay in therapy which is often begun when internal organ involvement is already irreversible. The ACR or LeRoy criteria have a low sensitivity for the early phases; these criteria were replaced by the ACR/EULAR 2013 criteria which improved the disease classification. Therefore, the SSc diagnosis may be delayed for several years after the onset of Raynaud’s phenomenon (RP) and even after the onset of the first non-RP symptom. RP, antinuclear antibodies (ANA) positivity, and puffy fingers were recently indicated as “red flags” (by the VEDOSS project) – that is, the main elements for suspicion of SSc in the very early phase of the disease. Confirming the diagnosis requires further tests, particularly nailfold videocapillaroscopy and evaluation of specific disease antibodies (anti-centromere and anti-topoisomerase I). In this way, the VEDOSS project identified patients in the very early phase of disease enabling a ‘‘window of opportunity’’ whereby the physician can act with effective drugs to block or at least slow the progression of the disease. The principal challenge in the fight against SSc is to detect valid predictors of disease evolution in order to treat patients in the early stage of disease. While waiting to find valid predictors, a close follow-up of the patients with the VEDOSS red flags is essential, as is a close collaboration between rheumatologists and general practitioners in order to identify all potential SSc patients as soon as possible.

Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites.  We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult onset still’s syndrome, are discussed. The present era of international travel poses a novel diagnostic and epidemiologic challenge and we must increase our awareness to the possibility of an exotic tropical infectious disease.

Background: Radiation-induced dermatitis is commonly seen during radiotherapy for breast cancer. Melatonin-based creams have shown a protective effect against ultraviolet-induced erythema and a radioprotective effect in rats.

Objectives: To evaluate the efficacy of melatonin-containing cream in minimizing acute radiation dermatitis. 

Methods: In this phase II, prospective, randomized, placebo-controlled double-blind study, patients who underwent breast-conserving surgery for stage 0-2 breast cancer were randomly allocated to melatonin emulsion (26 women) or placebo (21 women) for twice daily use during radiation treatment and 2 weeks following the end of radiotherapy. All women received 50 Gy whole breast radiation therapy with 2 Gy/fx using computed tomography-based 3D planning. Patients were examined and completed a detailed questionnaire weekly and 2 weeks following the end of treatment.

Results: The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients.

Conclusions: Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.

We present a literature review of collaborative enterprises between psychiatrists and primary care physicians in Israel and other countries. Also described are local psychiatric liaison initiatives in Israel, as well as landmark studies of collaborative psychiatric care. These studies demonstrate the superiority of community psychiatric liaison models in the treatment of patients suffering from depressive anxiety disorders and somatization disorder. In light of the mental health reform process currently underway in Israel, it is important to develop, implement and assess such liaison models. 

Background: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable.

Objectives: To evaluate the association of biomarkers with coronary and carotid disease.

Methods: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P < 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated.

Conclusions: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

 

Background: Various vena cava filters (VCF) are designed with the ability to be retrieved percutaneously. Yet, despite this option most of them remain in the inferior vena cava (IVC). 

Objectives: To report our experience in the placement and retrieval of three different types of VCFs, and to compare the indications for their insertion and retrieval as reported in the literature.

Methods: During a 5 year period three types of retrievable VCF (ALN, OptEase, and Celect) were inserted in 306 patients at the Rabin Medical Center (Beilinson and Hasharon hospitals). Indications, retrieval rates, median time to retrieval, success and complications rate were viewed and assessed in the three groups of filter types and were compared with the data of similar studies in the literature.

Results: Of the 306 VCFs inserted, 31 (10.1%) were retrieved with equal distribution in the three groups. In most patients the reason for filter insertion was venous thromboembolic events (VTE) and contraindications to anticoagulant therapy. Mean age was 68.38 ± 17.5 years (range 18–99) and was noted to be significantly higher compared to similar studies (53–56 years) (P < 0.0001). Multi-trauma patients were significantly older (71.11 ± 14.99 years) than post-pulmonary embolism patients (48.03 ± 20.98 years, P < 0.0001) and patients with preventive indication (26.00 ± 11.31, P < 0.0001). The mean indwelling time was 100.6 ± 103.399 days. Our results are comparable with the results of other studies, and there was no difference in percentage of retrieval or complications between patients in each of the three groups. 

Conclusions: In 1 of 10 patients filters should be removed after an average of 3.5 months. All three IVC filter types used are safe to insert and retrieve.

 

Background: The timing of interval laparoscopic cholecystectomy continues to be a matter of debate. 

Objectives: To evaluate the best timing for performing this procedure after an episode of acute cholecystitis. 

Methods: In this retrospective analysis, we divided 213 patients into three groups based on the time that elapsed since an episode of acute cholecystitis to surgery: Group I: 1–6 weeks, Group II: 6–12 weeks, Group III: > 12 weeks. 

Results: The mean operative time ranged from 50 to 62 minutes, complication rate from 2.6% to 5.9%, conversion rate from 2.6% to 10.8%, length of hospitalization from 1.55 to 2.2 days, and the 30 day readmission rate from 2.7% to 7.9%. There were no statistically significant differences between the study groups in the primary outcome parameters.

Conclusions: Due to the lack of statistically significant differences between the groups, interval laparoscopic cholecystectomy can be performed safely and without increasing the complication rate within 6 weeks following the acute episode as well as 12 weeks after. However, a trend towards higher conversion and complication rates was observed in Group II (6–12 weeks).

 

Background: Successful neuraxial block performance relies on assessment and palpation of surface landmarks, potentially challenging in patients with high body mass index (BMI). 

Objectives: To evaluate the use of ultrasound-assisted neuraxial bock in a non-obstetric population with BMI above versus below 30 kg/m2.

Methods: Healthy adult patients undergoing extracorporeal shock wave lithotripsy (ESWL) under neuraxial block were observed in this quality assurance study. Prior to the neuraxial block, an ultrasound examination was performed to identify the puncture site. Neuraxial anesthesia block was performed under aseptic surgical conditions with the patient in the sitting position. Following block placement, external landmarks were palpated. Our primary study outcome was the number of attempts (skin insertions with the needle) after pre-puncture ultrasound identification of the insertion point, comparing patients with BMI above versus below 30 kg/m2. Our secondary outcome was assessment by palpation of external anatomical landmarks.

Results: Our study group included 63 consecutive patients undergoing neuraxial block for ESWL. Data were assessed according to BMI (above versus below 30 kg/m2). An overall success rate at the first attempt of 90.5% (CI 0.8–0.95) was achieved using ultrasound-guided neuraxial block. This block placement success rate was similar for all patients, regardless of BMI above versus below 30 kg/m2. In contrast, the ease of palpation of anatomic landmarks, P = 0.001, and the ease of palpation of iliac crest, P < 0.001, differed significantly between the patients above versus below 30 kg/m2. The reported verbal pain scores (VPS) due to block insertion was similar among all patients regardless of BMI category (above versus below 30 kg/m2).

Conclusions: We observed high success rates when ultrasound-assisted neuraxial block is performed, regardless of BMI above versus below 30 kg/m2, despite expected differences in surface landmark palpation. 

 

Background: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. 

Objectives: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT 

Methods: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. 

Results: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). 

Conclusions: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by lack of education and depression. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy. 

 

Background: Despite awareness regarding tubal pregnancy, ovarian pregnancy still remains a diagnostic challenge. The correct diagnosis is most frequently made intraoperatively and requires histopathologic confirmation. Therefore, additional diagnostic measurements are needed for earlier and more accurate detection of ovarian pregnancies which will allow more rapid and efficient treatment. 

Objectives: To assess the time trends, clinical manifestations, surgical management and post-procedure outcome of 46 primary ovarian pregnancies in a single institution during three time periods.

Methods: In this retrospective study we compared 20 patients with primary ovarian pregnancy during the years 1971–1989 (first period), 19 patients in 1990–2001 (second period) and 7 patients in 2002–2013 (third period). In all cases the pathology examination confirmed primary ovarian pregnancy.

Results: The number of tubal ectopic pregnancies almost doubled, from 637 in the first period to 1279 in the third period (P < 0.001). However, there was a significant fall in the number of ovarian ectopic pregnancies, from 20 cases in the first period to 7 cases in the third (P = 0.009). A significant difference was noted when we compared the postoperative hospitalization time (4.06 ± 1.4 vs. 2.0 ± 0.6 days respectively, P = 0.001) in the second versus the third time period.

Conclusions: Ovarian pregnancy continues to be a diagnostic challenge, associated with a high rate of circulatory collapse, hemoperitoneum and requirements for blood transfusions, all leading to longer hospitalization.

 

Background: The kinetics of high sensitivity cardiac troponin T (hs-cTnT) levels after elective, biphasic, direct-current cardioversion for persistent atrial fibrillation/flutter remains unknown.

Methods: We examined hs-cTnT kinetics in 24 patients at baseline and at 2, 6 and 24 hours post-cardioversion, and again at 7 and 30 days. We also examined levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, brain natriuretic peptide (BNP), and high sensitivity C-reactive protein (hs-CRP).

Results: Median (25th, 75th interquartiles) baseline hs-cTnT concentration was 19.8 (10.4, 35.2) ng/L with 14 patients presenting with levels above the 99th percentile (13 ng/L). Hs-cTnT levels did not change significantly over time although they tended to decrease by 30 days, 18.8 ng/L (12.5, 23.3). There was no significant rise in other markers of myocardial injury. Similarly, BNP and hs-CRP levels were elevated at baseline and tended to decrease over time.

Conclusions: Patients with persistent atrial fibrillation/flutter have elevated hs-cTnT levels, as part of a general rise in biomarkers such as BNP and hs-CRP, without a further rise after cardioversion. After cardioversion, there is a gradual non-significant decrease in biomarker levels over time, and thus a rise in hs-cTnT levels should not be attributed to cardioversion. 

 

Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now® (TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. 

Objectives: To explore retrospectively the predictive value of TN for patients with colorectal and gastric carcinomas. 

Methods: The study group comprised colorectal and gastric carcinoma patients with TN test reports. We identified chemotherapy regimens given for stage IV disease for which TN reports indicated prediction. Protocols were classified as having clinical benefit (CB; i.e., stable disease or any objective response) or progressive disease, and this was compared with the TN prediction. 

Results: Nineteen patients – 12 colorectal and 7 gastric carcinomas – met the inclusion criteria. There were 26 evaluable treatment protocols; of 18 with a CB 15 were predicted to have a CB while 3 were predicted to have a lack of CB. Of eight protocols that had no CB, seven were predicted to have a CB and one was predicted to have a lack of CB. A chi-square test was non-significant (P = 0.78). An exploratory analysis yielded a positive predictive value of 68% and a sensitivity of 83% for the TN test. 

Conclusions: This study emphasizes the need for larger multicenter studies to validate the TN test before it is adopted into clinical practice.