Twenty five years of the National Academy of Medical Sciences of Ukraine - progress and priorities for future of radiation medicine and biology. / DVADTsIaT' P'IaT' ROKIV NATsIONAL'NOÏ AKADEMIÏ MEDYChNYKh NAUK UKRAÏNY ­ PROGRES TA PRIORYTETY NA MAY̆BUTNIe RADIATsIY̆NOÏ MEDYTsYNY TA RADIOBIOLOGIÏ.

After the creation of the Academy of Medical Sciences of Ukraine in 1993 the Research Center for Radiation Medicine was among the first institutions to join the Academy (fig. 1). Estab lishing the Academy was among the first steps of the independent Ukrainian government and aimed to provide a high level health care for population. It was extremely needed for the minimization of Chornobyl medical consequences. This choice was related to a growing recognition of the scientific research in fulfilling the Сenter's mission - study of the effects of low dose radiation on human body and radiation protection of the exposed population.The Center entered the Academy as a potent insti tution. Director General Dr. Anatoly Romanenko and his first deputy prof. Oles Pyatak were lucky to concentrate in three institutes of the Center a talent ed workforce including director of the Institute of Clinical Radiology prof Volodymyr Bebeshko, director of the Institute of Epidemiology and Prophylaxis of radiation Injuries prof. Volodymyr Buzunov, director of the Institute of Experimental Radiology prof. Mikhail Rudnev. Drs. T. Azaren kova, S. Galkina, V. Boer, T. Treskunova were appointed as scientific secretaries. Dosimetry divi sion was headed by brilliant prof Ilya Likhtarev and his staff Drs. I. Los, V. Korzun, V. Repin, O. Pere voznikov, O. Bondarenko, V. Chumak and others.The Center met creation of the Academy with expe rienced research and clinical staff encountering 1587 members, including 272 research staff, 28 doctors of science and 98 PhDs, modern diagnostic and labo ratory equipment, 300 beds in clinical departments and construction of hospital and out patient hospi tal in Svyatoshin. Scientific staff included experi enced prof. I. Khomaziuk, prof. B. Prevarsky, prof. V. Zamostian, prof. P. Chayalo, prof. M. Omelya nets, prof. A. Prysyazhnyuk. Dr. A. Niagu, Dr. E. Stepanova, Dr. A.Chumak, Dr. V. Klymenko, Dr. D. Komarenko, M. Pilinska, L.Ovsiannikova, O. Pi rogova. were among the first academic supervisors in studies of Chornobyl health effects and got professor certificates in this new area. First PhD theses were successfully passed by Dr. E. Gorbov, and Dr. of Sciences - by Dr. D. Bazyka. Basics of future aca demic research directions were elaborated that time by Drs. O. Kovalenko, Zh. Minchenko, V. Talko, I. Holyavka, D. Belyi, D. Yakimenko, E. Mikhai lovska, V. Malyzhev, V. Sushko, A. Cheban, K. Lo ganovsky, K. Bruslova, I. Dyagil, T. Liubarets, O. Kucher, G. Chobotko, and others. Later the major ity of these studies formed a background for Chornobyl legislation, regulatory directives, pre sented as dissertations.A quarter of century passed. The Center as a part of the National Academy of Medical Sciences resisted the challenges and moved forward, was recognized worldwide and fulfilled its main mission - providing highly qualified health care to radiation exposed. Staff numbers decreased (1,091), but work amount has increased. Since 2000, new premises were installed - a hospital with the biggest in Ukraine outpatient clin ic, new laboratory facilities, the last of which was in troduced in 2013. The Academy became a national one and since 2011 the Center was recognized as a national research institution (NRCRM), staff mem bers received 3 State Awards of Ukraine in the Field of Science and Technology, numerous personal awards.During this period, NRCRM staff conducted and published priority research data on radiation risks and molecular mechanisms of leukemia, including chronic lymphocytic, myelodysplastic syndrome, multiple myeloma, thyroid cancer, breast cancer in Chornobyl accident cleanup workers. Studies of the mechanisms of non tumor pathology - cardio vascular, cerebrovascular, cognitive disorders are in process. Of high importance are studies of possible transgenerational effects of radiation. The devel oped new technologies and protocols for the advanced care of radiation exposed were intro duced to the general health care system, the addi tional departments of oncology and chemotherapy were equipped and started activities, databases of cancer cases in exposed population and separate groups of exposed were introduced, as well as an international database of radiation injuries. The Clinical and Epidemiological registry of the NRCRM is in function and developed. An adapta tion of research directions with a respect to the pathomorphosis of radiation induced diseases in the remote period after irradiation will continue.Performed complex studies of the effects of incorporation of 131I on the fetus and the next gen eration of experimental animals became important for understanding the mechanisms of formation of radiation effects. Introduction of new foodstuffs and supplements with radiation protective proper ties was of positive effect for population protection during the first years.In the area of dosimetry a substantial progress has been achieved in reconstruction of thyroid doses in the Ukrainian population, dosimetric passportisation of settlements, radiochemistry, the creation of new methods for reconstructive dosimetry for cleanup workers - SEAD, RADRUE, and ROCKVILLE. All developments are implemented to practice, tens of thousands of doses have been restored. International recognition has received for the method of in utero doses reconstruction. As editor in chief, I regard it successful to incorporate our bilingual edition «Problems of Radiation Medicine and Radiobiology¼ into the NCBI MedLine, SCOPUS and other data bases, that creates an unique opportunity to widely disseminate results of the Center's research.Strategies for the future. Ukraine belongs to countries with a priority development of nuclear energy. Even with the increase in the production of clean energy, there is no other way than the further deployment of a complete nuclear fuel cycle and energy industrial complex, the expansion of the nuclear technologies to all sectors of the economy.The main potential threats to radiation safety include the aging of the material base of the NPPs with the prolongation of the working life for nuclear reactors with the expired terms of exploitation; the existence of a «nuclear legacy¼ sites of the former USSR in the territories of enterprises for the extrac tion and processing of uranium ores. About 5,000 institutions and enterprises use more than 25,000 sources of ionizing radiation in general. The use of radiological technologies and sources of ionizing radiation in medicine is increasing, in particular the burden on patients and staff in invasive cardiac sur gery. This will require significant efforts from the NRCRM to ensure an adequate radiation protec tion of the population, taking into account the experience collected during the mitigation of health effects of Chornobyl. Radiological threats of malev olent use of nuclear technology hasn't be forgotten.The mission of the NRCRM is to expand basic research of the health effects of ionizing radiation, elaboration and implementation of the care and radiation protection of population. Background for future is paved by a successful implementation of a special program of medical and biophysical control of personnel during transformation of the Shelter object into an environmentally safe sys tem, the State social program of increasing safty, labor hygiene and environment for 2014-2018; many years of successful cooperation with the State Nuclear Regulatory Inspectorate, the Natio nal Commission for Radiation Protection, «Ener goatom¼ company, the relevant departments of the Ministry of Health, international organizations such as WHO, UNSCEAR, IAEA, IARC, the US National Cancer Institute, IRSN, Nagasaki, Hiroshima, Fukushima universities and others.From the editorial board I congratulate the staff of the Center with the twenty fifth anniversary of the Academy. I would like also to wish the National Academy of Medical Sciences of Ukraine new ad vances in medical science and practice, sustainabil ity, unity, development and worldwide recognition.

Good riddance to the term "refractory anemia" in myelodysplastic syndromes.

The term "refractory anemia" was used in 1937 by Cornelius Parker Rhoads to describe patients whose anemia did not improve after treatment with liver extract or iron salts, and this term has been used to denote patients with certain subtypes of myelodysplastic syndromes (MDS) since the 1976 and 1982 French-American-British (FAB) classifications of acute leukemias and MDS. In 2016, the World Health Organization (WHO) proposed elimination of "refractory anemia" in a more general proposal for reclassification of myeloid neoplasia. A scandal relating to Dr. Rhoads' possibly unethical medical experiments on anemic patients in Puerto Rico in 1931 and a racially offensive letter he wrote during that period prompted an international incident and Congressional-level inquiry. This dark history, as well as continued terminological problems with refractory anemia, suggest that this hoary term has indeed worn out its usefulness. This article reviews the history of "refractory anemia" and evolution in its use over the past 80 years. Rhoads' personal history, the potentially confusing nature of "refractory anemia", and the fact that it is possible none of the 100 patients Rhoads described in 1937 actually had MDS all support the new WHO reclassification proposal to eliminate this term.

The myelodysplastic syndromes: a personal recollection of four decades of classification and prognostic scoring systems.

In 1976 the French-American-British (FAB) Leukemia Working Group proposed the first definitions of patients with myelodysplastic syndromes (MDS), namely refractory anemia with excess blasts (RAEB) and chronic myelomonocytic leukemia (CMML). Subsequent publications resulted in additional subgroups that had prognostic significance. Incorporation of the subgroupings by the World Health Organization and additional fine tuning of the degrees of morphologic dysplasia and percentage of blasts have enhanced the classification. Several prognostic scoring systems have added degrees of cytopenia, cytogenetic aberrations and molecular genetic mutations that allow care providers to subdivide cases into lower, intermediate and higher grade categories.

Historical perspectives on myelodysplastic syndromes.

Although Georg Hegel quipped, "We learn from history that we do not learn from history", Aldous Huxley expressed a more nuanced view: "The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different." In order to understand present-day positions and peculiarities in any field of human endeavor, familiarity with the past is essential. Those of us who study myelodysplastic syndromes (MDS) or care for patients diagnosed with these troublesome conditions may wonder also how the current state of affairs evolved with respect to our narrow area of focus, and how we know what we think we know now about these still-enigmatic bone marrow diseases. Here, I review a number of developments that collectively represent a brief "history of MDS." I first highlight a few landmark observations that preceded any concept of MDS by hundreds of years. Twentieth-century case descriptions and series with hypotheses about the etiology and nature of disorders described as "refractory anemia", "preleukemia", and with other terminology culminated in the efforts of the French-American-British (FAB) Co-operative Group of morphologists, whose landmark 1976 and 1982 papers provided the first widely-used classification of MDS. More recent developments in the MDS field include new mechanistic biological insights, regulatory approval of several somewhat-effective treatments, and improved organizational support and advocacy. The history of a disease concept like MDS, as for history in general, provides both inspiration and cautionary tales that can inform present and future work.

Will to live.

Review of David Rieff's Swimming in a sea of death: a son's memoir. Rieff is the son of writer Susan Sontag.

"Pawn Ball Megakaryocytes": from the marvellous medici and dear Old Saint Nick to the unsanctified marrow of myelodysplasia.

The worlds of biology and medicine in general, and the discipline of hematology in particular, enjoy a rich lexicon full of fascinating etymologies. The term "Pawn Ball Megakaryocytes" has been used to describe a peculiar type of abnormal cell that can be found in bone marrow samples taken from some patients with the myelodysplastic syndrome (MDS). The three-ball pawnbroker's symbol that these megakaryocytes resemble is ancient and may have derived from the insignia of the Medici family or the symbol of Saint Nicholas of Myra. The murky history of the symbol and its significance for myelodysplasia are reviewed.

Aplastic anemia before bone marrow transplantation and antilymphocyte globulin.

In severe aplastic anemia, disease-dependent mortality was high before allogeneic bone marrow transplantation (BMT) and immunosuppressive therapies (IST) including antilymphocyte globulin became available. However, under supportive therapy alone, spontaneous remissions were observed in up to 20% of severe cases, reflecting the natural course of the disease. Therefore, in evaluating new forms of treatment, one has to keep in mind that remission is not necessarily response, and that final proof of utility of any new therapy still requires a randomized study design. Transition to leukemia or myelodysplasia was rarely observed if the initial diagnosis was accurate. The much higher incidence of leukemias in patients treated by IST, but not by BMT is probably due to the better life expectancy of patients at risk, rather than to a leukemogenic potential of IST itself. 'Outdated' therapeutic modalities, such as androgens or splenectomy, may still be justified as an adjuvant therapy in selected cases.