Israel Medical Association Journal

Background: Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association.

Objectives: To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations.

Methods: Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a β2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of β2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates.

Results: In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: “inflammatory response,” “immune response,” “response to stress,” “oxydoreductase activity,” “metalloendopeptidase activity,” and “cytokine/chemokine activity.” As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated.

Conclusions: Given the inflammatory response evinced at gene expression analysis on decidual stromal cells treated with a β2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.

 

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.

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Background: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.

 

Background: Transvenous lead extraction can lead to tricuspid valve damage. 

Objectives: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction.

Methods: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR.

Results: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8–93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%).

Conclusions: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined. 

 

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: Gallbladder (GB) cancer is rare. Most cases are incidentally found in specimens after a cholecystectomy. Cholelithiasis is almost always present when this diagnosis is made. Obesity is a known risk factor for gallstone formation and thus may be related to GB cancer. 

Objectives: To highlight the importance of evaluation of the gallbladder before surgery, resection of the gallbladder whenever required, and screening the resected tissue for malignancy.

Methods: We retrospectively queried a prospectively maintained database of all bariatric procedures during the last 8 years for cases of concomitant laparoscopic sleeve gastrectomy (LSG) and laparoscopic cholecystectomy (LC). Pathologic reports of the gallbladders were reviewed. Demographic data and perioperative parameters were documented. 

Results: Of 2708 patients reviewed, 1721 (63.55%) were females and 987 (36.45%) males. Excluded were 145 (5.35%) who had a previous cholecystectomy. Of the remaining 2563, 180 (7.02%) had symptomatic gallbladder disease and underwent LSG with LC. Of these, two females (BMI 53 kg/m² and BMI 47 kg/m², both age 60) were found by histological examination to have adenocarcinoma in their GB specimens (1.11%). Both were reoperated, which included partial hepatectomy of the GB bed, resection of the cystic stump, lymph node dissection, and resection of the port sites. One patient is doing well, with no evidence of disease at a postoperative follow-up of 4 years. The second patient had recurrent disease with peritoneal spread and ascites 20 months post-surgery and died 18 months later. 

Conclusions: GB cancer is a rare finding in cholecystectomy specimens. The incidence of this entity might be higher in obese older females owing to the higher incidence of cholelithiasis in these patients. 

 

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: Obesity causes specific sexual problems, including diminished sexual desire, poor performance and avoidance of sexual encounters.

Objectives: To systematically evaluate the effect of bariatric surgery on patients' sexual function as compared to their preoperative status.

Methods: Bariatric surgery candidates were given a validated sexual function questionnaire the day before surgery and again 1 year after surgery. Females were polled with the Female Sexual Function Index (FSFI) and males with the Brief Sexual Function Inventory (BSFI). Statistical analysis was performed to elucidate differences in response to the questionnaires.

Results: The study population included 34 females and 14 males. Mean age and body mass index (BMI) were 40.2 ± 10.2 years and 43.4 ± 5.3 kg/m2, respectively. Postoperative BMI was 31.4 ± 4.9 kg/m2 (P < 0.001). Laparoscopic sleeve gastrectomy was performed in 36 patients and laparoscopic Roux-y gastric bypass in 12. In females, the FSFI index rose significantly from 24 to 30 (P = 0.006), indicating increased sexual performance and satisfaction. In males the BSFI increased from 40.2 to 43.9 but did not reach statistical significance (P = 0.08). However, general satisfaction, desire and erection were each significantly improved within the BSFI.

Conclusions: In addition to the well-documented medical and quality-of-life benefits of bariatric surgery, there is also clear improvement in patients' sexual function, both physical and psychosexual.

 

Background: Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. 

Objectives: To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department.

Methods: The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by metered dose inhaler (100 μg/puff) attached to a spacer device. The number of puffs was determined by severity of disease according to GINA recommendations. After 2 years the outcome and cost analysis were examined.

Results: During 3 years since the initial policy change 92.5% patients were treated with spacers throughout their hospital stay (emergency department and pediatric ward). Costs were reduced by an estimated 63%. 

Conclusions: In view of its many advantages the replacement of nebulizers by MDI+S for the treatment of acute asthma is feasible, if performed in collaboration with the staff, hospital authority and patients.

 

Background: Benign prostate hyperplasia (BPH) is a common age-dependent urological condition that can disrupt quality of life if the patient's treatment choice is inappropriate. 

Objectives: To examine whether patients’ demography and personality affect their decision regarding the type of treatment: namely, conservative or surgical. 

Methods: A total of 105 BPH patients treated during the period 2005–2008 were retrospectively categorized into three groups according to treatment received: (i) medication only (n=056), (ii) combined treatment (the initial medication treatment was switched to surgical treatment) (n=32), and (iii) surgery only (n=17). A prerequisite for inclusion in the study was use of BPH medication for at least half a year before the study (groups 1 and 2). These groups completed the International Prostate Symptom Score (IPSS) questionnaire at the start of BPH medical treatment (IPSS 1) and at the start of the trial (IPSS 2), and the staff calculated the difference (IPSS 1-IPSS 2 = Delta IPSS = DIPSS).  All three groups provided demographic data (age, country of origin, education) and completed tri-dimensional personality questionnaires (TPQ) to measure three independent "temperament" personality dimensions to evaluate how different individuals feel or behave: novel seeking (NS), harm avoidance (HA), and reward dependence (RD). Data were analyzed using chi-square, t-test, one-way ANOVA and logistic regression.

Results: Demographic variables and the RD dimension differed according to choice of BPH treatment. 

Conclusions: Our study suggests that symptomatic BPH treatment is influenced less by the patient's personality and more by his life circumstances. Israeli-born patients were more conservative, Russian-born patients were ambivalent, and other foreign-born patients predominantly preferred surgical treatment. We assume that personality has a more decisive effect on patients with malignant disease and they accept the medical advice more easily. 

 

Background: While earlier studies indicated that cholesterol levels decrease significantly after an acute myocardial infarction (MI), a more recent study refuted this observation. 

Objectives: To assess changes in plasma lipid levels after onset of acute MI, and determine important predictors of lipid dynamics.

Methods: We prospectively measured lipid levels of patients who presented with an acute MI. Blood samples were drawn on admission to the hospital (day 1), after fasting at least 12 hours overnight (day 2), and on the 4th day of hospitalization (day 4). 

Results: Of 67 acute MI patients, 30 were admitted for ST elevation MI (STEMI) and 37 for non-STEMI. Both total cholesterol and low density lipoprotein cholesterol (LDL-C) levels decreased significantly (by 9%) in the 24 hours after admission and by 13% and 17% respectively on day 4. High density lipoprotein cholesterol (HDL-C) levels as well as triglycerides did not change significantly. Independent predictors of LDL-C decrease were the presence of diabetes mellitus [odds ratio (OR) 6.73, P = 0.01), and elevated cardiac troponin T (cTnT) levels (OR 1.81, P < 0.04).

Conclusions: LDL-C levels decrease significantly after an acute MI. The reduction is correlated with cTnT levels. Diabetes is a strong independent predictor of LDL-C decrease. In acute MI patients only measurements taken within 24 hours of onset should be used to guide selection of lipid-lowering medication.