Israel Medical Association Journal

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

Objectives: To investigate whether young patients, i.e., under age 50, complain of symptoms for longer than older patients until the diagnosis of colon cancer is established.

Methods: In this retrospective cohort study, patients were divided into two groups: < 50 years old (group 1) and ≥ 50 (group 2). All had undergone surgery for left or right colon cancer during the 1 year period January 2000 through December 2009 at one medical center. Rectal and sigmoid cancers were excluded. Data collected included age, gender, quantity and quality of complaints, duration of complaints, in-hospital versus community diagnosis, pathological staging, the side of colon involved, and overall mortality. The main aim was the quality and duration of complaints. Secondary outcomes were the pathological stage at presentation and the mortality rate.

Results: The study group comprised 236 patients: 31 (13.1%) were < 50 years old and 205 (86.9%) were ≥ 50 years. No significant difference was found in the quantity and quality of complaints between the two groups. Patients in group 1 (< 50 years) complained for a longer period, 5.3 vs. 2.4 months (P = 0.002). More younger patients were diagnosed with stage IV disease (38.7% vs. 21.5%, P = 0.035) and fewer had stage I disease (3.2% vs. 15.6%, P = 0.06); the mortality rates were similar (41.9% vs. 39%). Applying a stepwise logistic regression model, the duration of complaints was found to be an independent predictor of mortality (P = 0.03, OR 1.6, 95% CI 1–3.6), independently of age (P = 0.003) and stage (P < 0.001).

Conclusions: Younger patients are more often diagnosed with colon cancer later, at a more advanced stage. Alertness to patients’ complaints, together with evaluation regardless of age but according to symptoms and clinical presentation are crucial. Large-scale population-based studies are needed to confirm this trend. 

Background: Corneal haze is a significant complication of photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK).

Objectives: To evaluate the effect of ascorbic acid supplementation in addition to perioperative topical mitomycin-C for the prevention of haze after LASEK.

Methods: We performed a retrospective, non-randomized case series study of two groups of 48 consecutive patients (96 myopic eyes) who had LASEK surgery. The treatment group was given ascorbic acid (vitamin C) orally 500 mg twice daily from 1 week before to 2 weeks after surgery. The control group was not offered any additional treatment. Ascorbate supplementation was the only difference in the postoperative treatment protocol between the treatment and control groups. Haze was assessed on a scale from 0 to 4 at the 1 year visit.

Results: Overall, 33.3% and 37.5% of the patients in the treatment and control groups respectively developed corneal haze. The trend of increased haze severity in the control group did not reach statistical significance.

Conclusions: Our results showed that systemic ascorbate supplementation does not have an additional effect on the prevention of haze after LASEK compared to the effect of topical mitomycin-C alone.

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Whereas procoagulation abnormalities in acute stress are well established, little is known about the mechanism of hypercoagulation in chronic stress, such as post-traumatic stress disorder (PTSD). This is crucial, given the fact that chronic coagulation disturbances have been associated with increased morbidity and premature mortality due to thromboembolism and cardiovascular disorders, complications recently described in PTSD patients.

Objectives: To explore the mechanisms of hypercoagulation in chronic PTSD.

Methods: Thirty patients diagnosed with chronic PTSD were enrolled and compared with a control group matched for age, gender and ethnicity. Hypercoagulation state was evaluated by levels of fibrinogen, D-dimer, prothrombin fragment F 1+2, von Willebrand factor (vWF) antigen, factor VIII activity, activated protein C resistance, ProC Global assay, and tissue factor antigen. Psychiatric evaluation was performed using the Mini-International Neuropsychiatric Interview and Clinician Administered PTSD Scale (CAPS).

Results: vWF antigen levels were significantly higher in patients with chronic PTSD compared with the controls (121.3 ± 42 vs. 99.7 ± 23, respectively, P = 0.034). Higher levels of vWF antigen and factor VIII activity were found in patients with severe chronic PTSD (CAPS > 80), compared to controls and patients with chronic PTSD and less severe symptoms (CAPS ≤ 80). However, no differences were observed in any other studied coagulation parameters between patients and controls.

Conclusions: Increased levels of vWF antigen and factor VIII activity were documented in severe chronic PTSD. These findings suggest that the higher risk of arterial and venous thromboembolic events in PTSD patients could be related to endothelial damage or endothelial activation.
 

Background: The incidence of congenital heart defects, reported to be 5–8/1000 in term infants, is not well established in very low birth weight infants.

Objectives: To establish the incidence of congenital heart defects in VLBW[1] infants in the neonatal intensive care unit of our institution.

Methods: A retrospective analysis of the population in the NICU[2] at our institution was performed. VLBW (BW ≤ 1500 g) infants born between 2001 and 2006 who survived more than 48 hours were included in the study. Infants with clinical signs of heart disease underwent echocardiography.

Results: During the study period 437 VLBW live-born infants met the inclusion criteria. Of these, 281 (64.3 %) underwent echocardiography. CHD[3] was detected in 19 infants (4.4%, 95% confidence interval 2.4–5.4%), significantly higher than the incidence of 5–8/1000 in the general population (P < 0.0001). In the subgroup of 154 infants with BW < 1000 g there were 10 (6.5%) with CHD. In the subgroup of 283 infants with BW 100–-1500 g there were 9 (3.2 %, P = 0.19 vs. VLBW) with CHD.

Conclusions:  Our observations show an increased incidence of CHD in VLBW neonates, as compared to the general population. Since not all infants underwent echocardiography, and minor cardiac defects may have been missed in our VLBW infants, the true incidence may be higher than reported here.

Background: Injury to patent grafts or cardiac chambers may occur during reoperation after coronary artery bypass grafting. Preoperative spatial localization of bypass grafts with computed tomography may improve the safety of these procedures.

Objectives: To characterize patients who undergo CT before repeat operations after previous coronary artery bypass grafting, and evaluate its benefit in terms of surgical outcome.

Methods: We compared 28 patients who underwent cardiac gated CT angiography before reoperation (CT group) to 45 re-do patients who were not evaluated with CT (no‑CT group).

Results: The two groups were similar in most preoperative and operative characteristics. The CT group, however, included more patients with patent saphenous vein grafts and fewer with emergency operations, acute myocardial infarction and need for intraaortic balloon pump support. During mid-sternotomy, there was no injury to grafts in the CT group, while there were two patent grafts and three right ventricular injuries in the no-CT group. There was no significant difference in perioperative mortality (3.6% vs. 8.9%). The overall complication rate in the CT group was 21.4% compared to 42.2% in the no‑CT group (P = 0.07). The only independent predictors of postoperative complications were diabetes mellitus, preoperative stroke and preoperative acute MI[1].

Conclusions: The patency and proximity of patent grafts to the sternum are well demonstrated by multidetector CT and may provide the surgeon with an important roadmap to avoid potential graft injury. A statistical trend towards reduced complications rate was demonstrated among patients who underwent CT angiography before their repeat cardiac operation. Larger series are required to demonstrate a statistically validated complication-free survival benefit of preoperative CT before repeat cardiac surgery.