23 research outputs found

    Radiation and the Risk of Chronic Lymphocytic and Other Leukemias among Chornobyl Cleanup Workers

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    Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear.
 Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation.
 Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose.
 Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews less than 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: less than –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure.
 Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

    Genomic characterization of chronic lymphocytic leukemia (CLL) in radiation-exposed Chornobyl cleanup workers

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    Background Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. Methods A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively). Results Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p < 0.05). No significant enrichment in copy-number abnormalities at del13q14, del11q, del17p or trisomy12 was identified in UR-CLL compared to other groups. Type of work performed in the Chornobyl zone, age at exposure and at diagnosis, calendar time, and Rai stage were significant predictors of total genetic lesions (all p < 0.05). Tumor telomere length was significantly longer in UR-CLL than in UN-CLL (p = 0.009) and was associated with the POT1 mutation and survival. Conclusions No significant enrichment in copy-number abnormalities at CLL-associated genes was identified in UR-CLL compared to other groups. The novel associations between radiation exposure, telomere maintenance and CLL prognosis identified in this unique case series provide suggestive, though limited data and merit further investigation

    Outcome Prediction in Patients with Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation—A Retrospective International Multicenter Study

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    The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. Methods: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) Score, and 30-day survival. Results: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic—AUROC) ranged between 0.548 and 0.605. Conclusions: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V-V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO

    Implementation and outcomes of an urban mobile adult extracorporeal life support program.

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    ObjectiveAlthough extracorporeal life support (ECLS) has been increasingly adopted as rescue therapy for cardiac and pulmonary failure, it remains limited to specialized centers. The present study reports our institutional experience with mobile ECLS across broad indications, including postcardiotomy syndrome, cardiogenic shock, and COVID-19 acute respiratory failure.MethodsWe performed a retrospective review of all patients transported to our institution through our mobile ECLS program from January 1, 2018, to January 15, 2021.ResultsOf 110 patients transported to our institution on ECLS, 65.5% required venovenous, 30.9% peripheral venoarterial, and 3.6% central venoarterial support. The most common indications for mobile ECLS were acute respiratory failure (46.4%), COVID-19-associated respiratory failure (19.1%), cardiogenic shock (18.2%) and postcardiotomy syndrome (11.8%). The median pre-ECLS Pao2:Fio2 for venovenous-ECLS was 64 mm Hg (interquartile range [IQR], 53-75 mm Hg) and 95.8 mm Hg (IQR, 55-227 mm Hg) for venoarterial-ECLS, whereas median pH and base deficit were 7.25 (IQR, 7.16-7.33) and 7 mmol/L (IQR, 4-11 mmol/L) for those requiring venoarterial-ECLS. Patients were transported using a ground ambulance from 50 institutions with a median distance of 27.5 miles (IQR, 18.7-48.0 miles). Extracorporeal circulation was established within a median of 45&nbsp;minutes (IQR, 30-55&nbsp;minutes) after team arrival. Survival to discharge was 67.3% for those requiring venovenous-ECLS for non-COVID-19 respiratory failure, 52.4% for those with COVID-19%, and 54.1% for those requiring venoarterial-ECLS.ConclusionsPatients can be safely and expeditiously placed on ECLS across broad indications, utilizing ground transportation in an urban setting. Clinical outcomes are promising and comparable to institutional non-transfers and those reported by Extracorporeal Life Support Organization

    Dosimetry Support of the Ukrainian-American Case-control Study of Leukemia and Related Disorders Among Chornobyl Cleanup Workers

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    This paper describes dose reconstruction for a joint Ukrainian-American case-control study of leukemia that was conducted in a cohort of 110,645 male Ukrainian cleanup workers of the Chornobyl (Chernobyl) accident, who were exposed to various radiation doses over the 1986-1990 time period. Individual bone-marrow doses due to external irradiation along with respective uncertainty distributions were calculated for 1,000 study subjects using the RADRUE method, which employed personal cleanup history data collected in the course of an interview with the subject himself if he was alive or with two proxies if he was deceased. The central estimates of the bone-marrow dose distributions range from 3.7Ă—10(-5) to 3,260 mGy, with an arithmetic mean of 92 mGy. The uncertainties in the individual stochastic dose estimates can be approximated by lognormal distributions; the average geometric standard deviation is 2.0
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