Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot

Objectives

Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury.

Methods

This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years).

Results

Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p < 0.05). Presence of foreign particles in shrapnel injured patients has a negative impact on the surgical outcome in terms of rate of pain improvement (28 % compared to 67 % in patients with and without foreign particles, respectively). Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later.

Conclusions

This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient’s functional activity and quality of life.     

Predictive factors for latency period and a prognostic model for survival in patients with therapy‐related acute myeloid leukemia

Therapy‐related acute myeloid leukemia (t‐AML) is an increasingly recognized sequela in patients receiving chemotherapy or radiotherapy for a primary malignancy or autoimmune disease. This study assessed factors related to the latency period (LP) between the antecedent disorder (AD) and t‐AML diagnosis and developed a comprehensive prognostic model to predict overall survival (OS). We evaluated a cohort of newly diagnosed t‐AML patients treated with cytarabine‐based induction therapy from 2001 to 2011. Multivariable linear and proportional hazards models were used to assess the impact of different classes of chemotherapy on the LP and to identify independent prognostic factors for OS. Of 730 treated AML patients, 58 (7.9%) had t‐AML. Median LP to t‐AML was 5.6 years (range, 0.5–38.4). 64% of patients achieved CR and median OS was 10.7 months. Independent prognostic factors of short LP were age at AD (P < 0.0001) and prior treatment with mitotic inhibitors (P = 0.05). Unfavorable cytogenetics (P = 0.004), antecedent hematologic or autoimmune disease (P = 0.01), age >60 (P = 0.03), and platelet count <30,000 μL (P = 0.04) at the time of t‐AML diagnosis were prognostic for inferior OS. A prognostic model using these factors was developed that risk stratified t‐AML patients into two groups: favorable and unfavorable. Patients in the favorable group had a median OS of 37.6 months compared with 6.4 months in patients comprising the unfavorable group (P < 0.0001). Multicomponent prognostic models integrating disease or treatment‐related covariates can help better understand how t‐AML evolves; and can be clinically useful in risk stratifying t‐AML patients undergoing induction therapy. Am. J. Hematol. 89:168–173, 2014. © 2013 Wiley Periodicals, Inc.     

Pneumococcal vaccine targeting strategy for older adults: Customized risk profiling

Background

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting.

Methods

Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008–2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting.

Results

In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia.

Conclusions

We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns.     

The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children

Background

It was previously demonstrated that MMRV vaccine causes a higher rate of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors for FC include age, familial tendency, day care attendance, viral diseases, complications at birth and developmental delay.

Objective

We evaluated the relative and attributable risk of FC for vaccinees’ age, ethnicity, low birth weight, preterm birth and MMRV vaccination in 10–24 months old children.

Methods

Data on medical history and vaccination were extracted from data warehouses of Clalit Health Services and Israel's Ministry of Health and linked on an individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective study design was used to reveal the risk factors associated with FC in study participants.

Results

During the second week after immunization, an elevated relative risk of FC was demonstrated in MMRV-recipients (adjusted RR = 2.16 (95%CI: 1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day observation period did not differ between the MMR and MMRV vaccinees. The MMRV-specific attributable risk of FC was not statistically significant at any point of observation period and was exceedingly low compared to other risk factors, equaling 5.3 FC cases per 10,000 vaccinees (95%CI: −1.4; 12.2).

Discussion

Our findings demonstrate that MMRV-associated FC in 10–24 months old contributes very marginally to the overall rate of FC in this population.

Conclusion

Given the low number of MMRV-specific FC cases, their transient nature and the benefit of vaccination, the overall benefit-risk of the vaccine can be considered favourable. Nonetheless, the option of separate immunization with MMR + V should be offered to parents, in order to maintain sufficient vaccine uptake in the population.     

Risk factors and maternal outcomes following preterm premature rupture of membrane in the second trimester of gestation

Archives of Gynecology and Obstetrics - To characterize the population of women who underwent mid-trimester preterm premature rupture of membrane (PPROM) in a country where mid-trimester abortions...     

Feasibility Study of Automated Overnight Closed-Loop Glucose Control Under MD-Logic Artificial Pancreas in Patients with Type 1 Diabetes: The DREAM Project

Abstract Background: Artificial pancreas systems may offer a potential major impact on the normalization of metabolic control and preventing hypoglycemic events. This study aims to establish near-normal overnight glucose control and reduce the risk of nocturnal hypoglycemia using the MD-Logic Artificial Pancreas (MDLAP), an algorithm that was developed by our research group. This inpatient feasibility study is the first step towards implementing an overnight closed-loop MDLAP system at the patient's home. Subjects and Methods: Seven patients with type 1 diabetes (three adolescents and four adults; mean±SD age, 20.6±4.7 years; duration of diabetes, 9.6±2.6 years; body mass index, 24.3±3.9 kg/m(2); and glycated hemoglobin, 7.8±0.8%) participated in a total of 14 closed-loop overnight sessions. Each participant underwent two closed-loop inpatient sessions starting at dinner alone and at dinner following exercise. The closed-loop inpatient sessions were compared with data derived from nights spent at home with an open-loop system in a similar scenario to the study protocol. Results: The mean percentage of time spent in the near normal glucose range of 63-140?mg/dL was 83±16%, and the median (interquartile range) was 85% (78-92%) for the overnight closed-loop sessions compared with 34±31% and 27% (6-57%) in the homecare open-loop setting, respectively. During the overnight closed-loop sessions at dinner alone 92±9% of the sensor values ranged within target range, compared with 73±19% for the sessions following exercise (P=0.03). No hypoglycemic (<63?mg/dL) events occurred during the closed-loop sessions. Conclusion: Closed-loop insulin delivery under MDLAP is a feasible and safe solution to control overnight glycemia.