Israel Medical Association Journal

Background: Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN.

Objectives: To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event.

Methods: The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction.

Results: Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2.

Conclusions: A high proportion of patients presenting with “idiopathic” major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

Objective: To assess the impact of multiple births on the severity of RSV infection and define risk factors for acquiring RSV infection in infants of multiple birth.

Methods: Clinical data on infants hospitalized with RSV infection between 2008 and 2010 were retrospectively collected.

Results: Twins comprised 7.6% (66/875) of hospitalized infants with RSV bronchiolitis during the study period. Infants in the twin group were younger (122.4 ± 131.7 vs. 204.5 ± 278.8 days, P = 0.014), had a lower mean gestational age (35.3 ± 2.6 vs. 38.6 ± 2.5 weeks, P < 0.001), and were more likely to have been born prematurely compared with singleton infants (65.6% vs. 13%, P < 0.001). On a multivariable logistic regression analysis, young age, early gestational age and male gender were the only variables identified as risk factors for pediatric intensive care unit admission (P < 0.001, P < 0.001 and P = 0.03, respectively). In contrast, the mere fact of a child being a twin was not found to be a significant risk factor for disease severity. In addition, if one twin is hospitalized due to RSV infection, the other has a 34% chance of also being hospitalized with bronchiolitis. Young age was a significant risk factor for hospitalization of the second twin (P < 0.001).

Conclusions: Our findings suggest that twins hospitalized with RSV bronchiolitis do not have an increased risk for severe infection as compared to singletons. However, a twin of an infant hospitalized with RSV infection has a considerable risk of also being hospitalized with bronchiolitis, thus close monitoring is recommended. 

Objectives: To investigate the 30 day clinical outcome of the first 300 consecutive patients treated with transfemoral TAVI at the Tel Aviv Medical Center.

Methods: The CoreValve was used in 250 patients and the Edwards-Sapien valve in 50 patients. The mean age of the patients was 83 ± 5.3 years (range 63–98 years) and the mean valve area 0.69 ± 0.18 cm² (range 0.3–0.9 cm²); 62% were women.

Results: The procedural success rate was 100%, and 30 day follow-up was done in all the patients. The average Euro-score for the cohort was 26 ± 13 (range 1.5–67). Total in-hospital mortality and 30 day mortality were both 2.3% (7 patients). Sixty-seven patients (22%) underwent permanent pacemaker implantation after the TAVI procedure, mostly due to new onset of left bundle brunch block and prolonged PR interval or to high degree atrioventricular block. The rate of stroke was 1.7% (5 patients). Forty-one patients (13.7%) had vascular complications, of whom 9 (3%) were defined as major vascular complications (according to the VARC definition).

Conclusions: The 30 day clinical outcome in the first 300 consecutive TAVI patients in our center was favorable, with a mortality rate of 2.3% and low rates of stroke (1.7%) and major vascular complications (3%).

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 evaluate the predictive value regarding patients' survival once the diagnosis of “general deterioration” replaces an ICD-9 diagnosis upon re-admission.

Methods: In a retrospective cohort case-control study, we screened the records of patients re-admitted at least three times during the past 2 years. For each patient's death during the third hospitalization, we matched (for age and gender) a patient who survived the third hospitalization. We evaluated 14 parameters potentially accountable for increased risk of mortality, e.g., length of stay at each admission, interval to re-admission, etc. We applied a multifactorial analysis using logistic regression to predict the risk of mortality during the third hospitalization as potentially affected by the aforementioned parameters.

Results: The study included 81 study patients and 81 controls. Of the 14 parameters potentially explaining an increased risk of mortality during the third hospitalization, several were found to be statistically significant. The most significant was the diagnostic switch from a specific ICD-9 diagnosis on first admission to the non-specific diagnosis of “general deterioration” at the second hospitalization. In such cases, the risk of death during the third hospitalization was increased by 5300% (odds ratio = 54, P = 0.008). The increased risk of mortality was not restricted to patients with malignancy as their background diagnosis.

Conclusions: At re-admission, a switch from disease-specific diagnosis to the obscure diagnosis “general deterioration” increases the subsequent risk of mortality.

Background: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular medications. Bevacizumab is mostly used in this group of medications.

Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.

Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30–70 mmHg, 3–30 days after injection.

Results: Mean IOP was 42.6 mmHg (range 30–70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3–13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.

 Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments. 

Objectives: To devise a protocol to reduce the loss of pathology specimens.

Methods: In this study, 7105 specimens excised by one plastic surgeon were sent to the pathology laboratory using a strict protocol, which included: using a carefully labeled specimen container, inserting the specimen into the container immediately after excision (not at the end of the procedure), positioning the specimen container close to the surgical field during the surgery, and both the nurse and surgeon signing their names on the container at the end of the procedure to confirm the contents and labeling.

Results: One Mohs specimen was accidentally thrown away by a pathology laboratory technician after the frozen section report was written (an incidence of 1/7105, 0.00014%). All specimens arrived in the pathology department and no lesions were lost in the operating room.

Conclusions: A strict written protocol for specimen handling significantly reduces loss of pathology specimens.

Objectives: To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction.

Methods: Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score ≤ 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction.

Results: MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason`s score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. ;Conversely, when applying the most favorable preoperative conditions (Gleason ≤ 6, < 20% positive cores, MCL ≤ 11.5%) the chance of minimal disease was 41%.

Conclusions: Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance. 

Objectives: To evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at presentation, diabetic complications rate, and associated autoimmune diseases in a pediatric T1DM patient population in the Negev area.

Methods: Clinical and demographic details of 168 T1DM patients were evaluated, including HbA1C levels, long-term complications, related autoimmune diseases, and insulin pump usage. The data were analyzed and the Jewish and Bedouin patient groups compared.

Results: Only 13.1% of the patients had reached the HbA1C levels recommended by the current guidelines at the first and second year follow-up visits, and 9.5% and 7.1% at the third and fourth year visits, respectively. A significant difference in HbA1c levels between Jewish and Bedouin patients was found (P = 0.045 at the first year follow-up, P ≤ 0.01 thereafter). Significant difference was found between the Jewish and the Bedouin groups regarding presentation with DKA, 33% and 56% of the patients respectively (P = 0.01).

Conclusions: Existent glycemic control in daily practice is far from the guideline goals. Bedouin ethnicity was associated with less favorable diabetes control, emphasizing the need for better awareness of T1DM and its treatment options in this population. More resources should be directed to address T1DM in the general population, especially among the Bedouin.

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.