Preliminary results of a new boron coated neutron detector

The proliferation of neutron detection applications based upon 3He counter has triggered a critical shortage of 3He gas. Nowadays there is an increasing demand for alternative neutron detectors that can cover large solid angles, have low sensitivity to gamma background and low cost. We present a low cost neutron detector based upon 3 cm diameter, 150 cm long cylindrical metal tube coated on the inside with a thin layer of 10B-enriched boron carbide fulfilled by 1 atm nitroge

ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine

Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs

Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

195sinoneBackground: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.nonePagano L.; Salmanton-Garcia J.; Marchesi F.; Busca A.; Corradini P.; Hoenigl M.; Klimko N.; Koehler P.; Pagliuca A.; Passamonti F.; Verga L.; Visek B.; Ilhan O.; Nadali G.; Weinbergerova B.; Cordoba-Mascunano R.; Marchetti M.; Collins G.P.; Farina F.; Cattaneo C.; Cabirta A.; Gomes-Silva M.; Itri F.; van Doesum J.; Ledoux M.-P.; Cernan M.; Jaksic O.; Duarte R.F.; Magliano G.; Omrani A.S.; Fracchiolla N.S.; Kulasekararaj A.; Valkovic T.; Poulsen C.B.; Machado M.; Glenthoj A.; Stoma I.; Racil Z.; Piukovics K.; Navratil M.; Emarah Z.; Sili U.; Maertens J.; Blennow O.; Bergantim R.; Garcia-Vidal C.; Prezioso L.; Guidetti A.; del Principe M.I.; Popova M.; de Jonge N.; Ormazabal-Velez I.; Fernandez N.; Falces-Romero I.; Cuccaro A.; Meers S.; Buquicchio C.; Antic D.; Al-Khabori M.; Garcia-Sanz R.; Biernat M.M.; Tisi M.C.; Sal E.; Rahimli L.; Colovic N.; Schonlein M.; Calbacho M.; Tascini C.; Miranda-Castillo C.; Khanna N.; Mendez G.-A.; Petzer V.; Novak J.; Besson C.; Dulery R.; Lamure S.; Nucci M.; Zambrotta G.; Zak P.; Seval G.C.; Bonuomo V.; Mayer J.; Lopez-Garcia A.; Sacchi M.V.; Booth S.; Ciceri F.; Oberti M.; Salvini M.; Izuzquiza M.; Nunes-Rodrigues R.; Ammatuna E.; Obr A.; Herbrecht R.; Nunez-Martin-Buitrago L.; Mancini V.; Shwaylia H.; Sciume M.; Essame J.; Nygaard M.; Batinic J.; Gonzaga Y.; Regalado-Artamendi I.; Karlsson L.K.; Shapetska M.; Hanakova M.; El-Ashwah S.; Borbenyi Z.; Colak G.M.; Nordlander A.; Dragonetti G.; Maraglino A.M.E.; Rinaldi A.; De Ramon-Sanchez C.; Cornely O.A.; Finizio O.; Fazzi R.; Sapienza G.; Chauchet A.; Van Praet J.; Prattes J.; Dargenio M.; Rossi C.; Shirinova A.; Malak S.; Tafuri A.; Ommen H.-B.; Bologna S.; Khedr R.A.; Choquet S.; Joly B.; Ceesay M.M.; Philippe L.; Kho C.S.; Desole M.; Tsirigotis P.; Otasevic V.; Borducchi D.M.M.; Antoniadou A.; Gaziev J.; Almaslamani M.A.; Garcia-Pouton N.; Paterno G.; Torres-Lopez A.; Tarantini G.; Mellinghoff S.; Grafe S.; Borschel N.; Passweg J.; Merelli M.; Barac A.; Wolf D.; Shaikh M.U.; Thieblemont C.; Bernard S.; Funke V.A.M.; Daguindau E.; Khostelidi S.; Nucci F.M.; Martin-Gonzalez J.-A.; Landau M.; Soussain C.; Laureana C.; Lacombe K.; Kohn M.; Aliyeva G.; Piedimonte M.; Fouquet G.; Rego M.; Hoell-Neugebauer B.; Cartron G.; Pinto F.; Alburquerque A.M.; Passos J.; Yilmaz A.F.; Redondo-Izal A.-M.; Altuntas F.; Heath C.; Kolditz M.; Schalk E.; Guolo F.; Karthaus M.; Della Pepa R.; Vinh D.; Noel N.; Deau Fischer B.; Drenou B.; Mitra M.E.; Meletiadis J.; Bilgin Y.M.; Jindra P.; Espigado I.; Drgona L.; Serris A.; Di Blasi R.; Ali N.Pagano, L.; Salmanton-Garcia, J.; Marchesi, F.; Busca, A.; Corradini, P.; Hoenigl, M.; Klimko, N.; Koehler, P.; Pagliuca, A.; Passamonti, F.; Verga, L.; Visek, B.; Ilhan, O.; Nadali, G.; Weinbergerova, B.; Cordoba-Mascunano, R.; Marchetti, M.; Collins, G. P.; Farina, F.; Cattaneo, C.; Cabirta, A.; Gomes-Silva, M.; Itri, F.; van Doesum, J.; Ledoux, M. -P.; Cernan, M.; Jaksic, O.; Duarte, R. F.; Magliano, G.; Omrani, A. S.; Fracchiolla, N. S.; Kulasekararaj, A.; Valkovic, T.; Poulsen, C. B.; Machado, M.; Glenthoj, A.; Stoma, I.; Racil, Z.; Piukovics, K.; Navratil, M.; Emarah, Z.; Sili, U.; Maertens, J.; Blennow, O.; Bergantim, R.; Garcia-Vidal, C.; Prezioso, L.; Guidetti, A.; del Principe, M. I.; Popova, M.; de Jonge, N.; Ormazabal-Velez, I.; Fernandez, N.; Falces-Romero, I.; Cuccaro, A.; Meers, S.; Buquicchio, C.; Antic, D.; Al-Khabori, M.; Garcia-Sanz, R.; Biernat, M. M.; Tisi, M. C.; Sal, E.; Rahimli, L.; Colovic, N.; Schonlein, M.; Calbacho, M.; Tascini, C.; Miranda-Castillo, C.; Khanna, N.; Mendez, G. -A.; Petzer, V.; Novak, J.; Besson, C.; Dulery, R.; Lamure, S.; Nucci, M.; Zambrotta, G.; Zak, P.; Seval, G. C.; Bonuomo, V.; Mayer, J.; Lopez-Garcia, A.; Sacchi, M. V.; Booth, S.; Ciceri, F.; Oberti, M.; Salvini, M.; Izuzquiza, M.; Nunes-Rodrigues, R.; Ammatuna, E.; Obr, A.; Herbrecht, R.; Nunez-Martin-Buitrago, L.; Mancini, V.; Shwaylia, H.; Sciume, M.; Essame, J.; Nygaard, M.; Batinic, J.; Gonzaga, Y.; Regalado-Artamendi, I.; Karlsson, L. K.; Shapetska, M.; Hanakova, M.; El-Ashwah, S.; Borbenyi, Z.; Colak, G. M.; Nordlander, A.; Dragonetti, G.; Maraglino, A. M. E.; Rinaldi, A.; De Ramon-Sanchez, C.; Cornely, O. A.; Finizio, O.; Fazzi, R.; Sapienza, G.; Chauchet, A.; Van Praet, J.; Prattes, J.; Dargenio, M.; Rossi, C.; Shirinova, A.; Malak, S.; Tafuri, A.; Ommen, H. -B.; Bologna, S.; Khedr, R. A.; Choquet, S.; Joly, B.; Ceesay, M. M.; Philippe, L.; Kho, C. S.; Desole, M.; Tsirigotis, P.; Otasevic, V.; Borducchi, D. M. M.; Antoniadou, A.; Gaziev, J.; Almaslamani, M. A.; Garcia-Pouton, N.; Paterno, G.; Torres-Lopez, A.; Tarantini, G.; Mellinghoff, S.; Grafe, S.; Borschel, N.; Passweg, J.; Merelli, M.; Barac, A.; Wolf, D.; Shaikh, M. U.; Thieblemont, C.; Bernard, S.; Funke, V. A. M.; Daguindau, E.; Khostelidi, S.; Nucci, F. M.; Martin-Gonzalez, J. -A.; Landau, M.; Soussain, C.; Laureana, C.; Lacombe, K.; Kohn, M.; Aliyeva, G.; Piedimonte, M.; Fouquet, G.; Rego, M.; Hoell-Neugebauer, B.; Cartron, G.; Pinto, F.; Alburquerque, A. M.; Passos, J.; Yilmaz, A. F.; Redondo-Izal, A. -M.; Altuntas, F.; Heath, C.; Kolditz, M.; Schalk, E.; Guolo, F.; Karthaus, M.; Della Pepa, R.; Vinh, D.; Noel, N.; Deau Fischer, B.; Drenou, B.; Mitra, M. E.; Meletiadis, J.; Bilgin, Y. M.; Jindra, P.; Espigado, I.; Drgona, L.; Serris, A.; Di Blasi, R.; Ali, N