Journal articles on the topic 'Crisis stage diagnosis'
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1
Petrovici, Iasmina, Mihaela Ionica, and Octavian C. Neagoe. "Economic Crisis: A Factor for the Delayed Diagnosis of Breast Cancer." International Journal of Environmental Research and Public Health 18, no. 8 (April 10, 2021): 3998. http://dx.doi.org/10.3390/ijerph18083998.
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Considering the constant increase in breast cancer patients, identifying factors that influence the moment of diagnosis is essential for optimizing therapeutic management and associated cost. The purpose of the study is to evaluate the impact of the economic crisis on the moment of a breast cancer diagnosis. This retrospective observational study analyzed a cohort of 4929 patients diagnosed with breast cancer over the course of 19 years in the Western region of Romania. The time interval was divided based on the onset of the economic crisis into 3 periods: pre-crisis (2001–2006), crisis (2007–2012), and post-crisis (2013–2019). The disease stage at the moment of diagnosis was considered either early (stages 0, I, II) or advanced (stages III, IV). Although recording a similar mean number of patients diagnosed per year during the pre- and crisis periods, a significantly higher percentage of patients were diagnosed with late-stage breast cancer during the economic crisis period compared to the previous interval (46.9% vs. 56.3%, p < 0.01). This difference was further accentuated when accounting for environmental setting, with 65.2% of patients from a rural setting being diagnosed with advanced disease during the crisis interval. An overall improvement of 12% in early-stage breast cancer diagnosis was recorded in the post-crisis period (55.7%, p < 0.001). The findings of this study support periods of economic instability as potential factors for a delay in breast cancer diagnosis and highlight the need for the development of specific strategies aimed at reducing cancer healthcare and associated financial burden in times of economic crisis.
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Sharanov, Roman. "Enterprise Crisis Management Algorithm." Central Ukrainian Scientific Bulletin. Economic Sciences, no. 6(39) (2021): 288–96. http://dx.doi.org/10.32515/2663-1636.2021.6(39).288-296.
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The article devotes to the study of the enterprise crisis management process. In recent years, a large number of enterprises in Ukraine have suffered losses. This result related to both the internal problems in the country and the emergence of a new coronavirus crisis. Thus, in the conditions of unstable development of both world and domestic economy, the formation of the crisis management system is important for enterprises. Thus, the enterprise crisis management algorithm offered, which takes into account the peculiarities of the activity of small, medium and large business entities. The algorithm consists of the following stages: diagnostics of the business entity (small, medium, large), determining the crisis and its causes, developing a strategy to eliminate the threat, developing crisis measures to eliminate the threat, implementation of selected measures and monitoring their implementation, identifying the reasons for the ineffectiveness of measures (in case of overcoming the crisis) and eliminating the threat. There is a significant difference in crisis management between different businesses at the diagnostic stage. For small businesses, the diagnosis consists of assessing revenue, profitability, working capital. Diagnosis of medium-sized enterprises should be comprehensive and cover all areas of enterprise activity. Diagnosis of large enterprises consists of both comprehensive diagnostics and models for assessing the level of bankruptcy. Crisis management strategies and measures for small, medium and large businesses are common; however, the choice should take into account the possibility of their implementation in a particular enterprise. Depending on the stage of the crisis, the recommended strategies and crisis management measures. In consequence of the proposed algorithm, the company will be able to timely identify and overcome threats, and ensure continuous monitoring of its activities. It was indicated the practical significance of the above algorithm, which consists in early detection and consistent overcoming of problems in the activity of domestic enterprises in an unstable economic environment.
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Татар, Марина Сергіївна, and Ольга Михайлівна Козловська. "ВИЗНАЧЕННЯ ГЛИБИНИ КРИЗОВИХ ЯВИЩ БАНКІВСЬКИХ УСТАНОВ ТА РОЗРОБЛЕННЯ АНТИКРИЗОВИХ ЗАХОДІВ." TIME DESCRIPTION OF ECONOMIC REFORMS, no. 4 (January 27, 2020): 65–75. http://dx.doi.org/10.32620/cher.2019.4.09.
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In the current economic environment, due to economic and political instability, a large number of banks are unable to adequately respond to changes of external and internal environment, which can lead to crisis situations, so the problem of identifying patterns and causes of banking crises, as well as identifying opportunities to overcome them relevant. The aim of the research is development of theoretical and methodological provisions on the patterns of occurrence of banking crises and development practical recommendations on the use of methods and tools that can prevent and overcome crisis phenomena. The subject of the research is the regularity of the occurrence of banking crises and the implementation of the mechanism of banks anticrisis management. The methods of the research: analysis, synthesis, abstract and logical, comparative and statistical, generalization and grouping; structural, functional, integral method, etc. The hypothesis of the research. There is a need for differentiation of anti-crisis measures depending on the level of bank crisis state. The statement of basic materials. Factors of occurrence of banking crises are classified. The comprehensive approach to the diagnosis of crisis phenomena in the financial activity of banks has been developed. It is determined that in selecting the criteria and indicators for identifying the bank crisis state, differentiated approach should be used, which is based on the proposed system of indicators, which should reflect the level of bank capital adequacy, liquidity, financial stability, business activity, profitability and efficiency indicators of bank profitability and efficiency so the most important indicators of bank's activity. Preventive and reactive measures in the anticrisis management system of banks depending on the level of the crisis state are proposed. The originality and practical significance of the research is development a comprehensive approach to crisis diagnosis in bank operations on the bases of publicly available data obtained from the published financial statements of the bank. Conclusions and perspectives of further research. Crisis phenomena were diagnosed in the activity of PRAVEX BANK JSC, the complex of preventive and reactive measures of anti-crisis management of banks financial activity was developed, which is a set of methods and instruments aimed at achieving certain target targets, formulated according to crisis stage and depth.
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Liakh, Tetiana, Tetiana Spirina, and Tetiana Alieksieienko. "RECOMMENDATIONS ON SOCIAL SUPPORT TO FAMILIES AFFECTED BY HIV/AIDS." SOCIETY. INTEGRATION. EDUCATION. Proceedings of the International Scientific Conference 4 (May 20, 2020): 279. http://dx.doi.org/10.17770/sie2020vol4.4944.
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The purpose of this article is to provide recommendations for social workers and social field practitioners of state and non-governmental organizations working with families affected by HIV/AIDS. The article identifies a series of crisis stages of families affected by HIV/AIDS. Families caring for HIV-positive children go through four crisis stages. The first stage comes after the report about an unconfirmed possibility that a child has HIV. The second stage is when the diagnosis confirms the child’s HIV positive status. The third stage coincides with the first signs of opportunistic infections in the child. The fourth stage is associated with the progression of the disease and the development of the fourth clinical stage of HIV infection. At each of these stages, families need medical, psychological, and social support. In line with professional support, an effective method of assistance and a way to overcome a crisis can be self-help groups, in which people learn to voice their difficulties and problems, seek support or provide it to other families. Using the results of the study gained through focus groups with social work practitioners from various regions of Ukraine, the authors developed recommendations on supporting families affected by HIV/AIDS.
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Svyrydovа, N. K., and G. S. Lubenets. "Uncontrolled hypertension in patients with chronic ischemia of the brain." East European Journal of Neurology, no. 2(2) (December 20, 2015): 3–13. http://dx.doi.org/10.33444/2411-5797.2015.2(2).3-13.
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The incidence of hypertension is an independent risk factor for cerebrovascular disease. A special problem is uncontrolled hypertension, with the progression of which is 7 times more likely to develop chronic ischemia. At the present stage of diagnosis and treatment of uncontrolled hypertension hypertensive crises is the problem as critical state. Violation of cerebral hemodynamics and function of the brain in patients with chronic brain ischemia determine the clinical picture of hypertensive crisis complicated course. The article highlights the theoretical foundations of the mechanisms of etiopathogenetical, clinical course, diagnosis and modern aspects of the treatment of chronic brain ischemia in the development of hypertensive crisis. The results of their research on the changes of regional cerebral blood flow, cerebral blood flow parameters or transient change in the substance of the brain after hypertensive crises using modern research methods: daily monitoring of blood pressure and single photon emission computed tomography.
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Anklesaria, Pervin N., Suresh H. Advani, and Avinash N. Bhisey. "Studies on Granulocyte Functions in Patients with Chronic Myeloid Leukemia." Tumori Journal 71, no. 4 (August 1985): 317–23. http://dx.doi.org/10.1177/030089168507100401.
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Granulcoyte functions, viz. endocytosis, NADPH oxidase activity and iodination by leukocytes, were studied in granulocytes isolated from 17 chronic myeloid leukemia (CIVIL) patients at initial diagnosis (stage I), from 10 patients in relapse (stage II), and 10 patients in acute blastic crisis (stage III). The mean phagocytic index of granulocytes from CML patients was similar to the normal value. NADPH activity decreased as the disease progressed. Thus, the amount of formazan produced was lower in granulocytes from patients in stage II (P < 0.05) and stage III (P < 0.01) than that produced by normal granulocytes. H2O2-Myeloperoxidase-dependent iodination was found to be significantly reduced in granulocytes from all stages of the disease compared to that of normal, stage I (P < 0.01), stage II (P < 0.05) and stage III (P < 0.01). It thus seems that granulocyte function becomes less efficient as the disease progresses towards acute blastic crisis. Immature cells from the same patients carried out these functions at a more reduced level than did their mature counterparts.
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Carrington, Robbie, Andrzej Szymczakowski, and Akademia medyczna Medyczna. "Pulmonary oedema in hypertensive crisis - from failed femoral cannulation to diagnosis." Morecambe Bay Medical Journal 8, no. 4 (August 1, 2019): 118–20. http://dx.doi.org/10.48037/mbmj.v8i4.67.
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Pulmonary oedema is a very common clinical presentation in the hospital setting with the management steps memorised by most medical student from an early stage. This management works on the basis that the patient is fluid overloaded from left ventricular systolic dysfunction (LVSD). In reality however, this is not always the case with diastolic dysfunction also causing pulmonary oedema. In the case of diastolic dysfunction there is little data to guide management.1 We present a case of a patient who developed flash pulmonary oedema (FPO) secondary to a hypertensive crisis.
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Mihalachi, Ruslan, and Natalia Bancila. "A SYSTEMIC APPROACH TO ENTERPRISE CRISIS MANAGEMENT IN THE CURRENT ECONOMIC CONDITIONS." MEST Journal 9, no. 1 (January 15, 2021): 135–45. http://dx.doi.org/10.12709/mest.09.09.01.16.
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Crises are characteristic of any system, including economic entities in the process of its evolution. These usually signal the accumulation of a critical mass - of the restriction factors, the elimination or activation of which is necessary, either to prolong the reproduction process or to move to a new quality. The recent global economic crisis, related to the global pandemic situation, has made crisis management at both macro-economic and micro-economic levels one of the most important management tools to revive the critical situation globally. The crisis at all levels is always accompanied by a chronic organizational and financial instability, determining the need to develop measures that would be coherent in the new conditions of the economic environment accompanied by the political and social. The critical situation in the country's economy is confirmed by the worsening financial situation of domestic enterprises, the increase in losses, and, respectively, the number of enterprises on the verge of bankruptcy. Such a critical situation makes the issue of efficient organization of the management of the activity of enterprises in economic difficulty/crisis extremely topical. From this point of view, choosing the methods of crisis management and transforming them into an effective tool in entrepreneurship is a priority. The decisive role, in this sense, must belong to the diagnosis and financial forecasting of the dangers of crises at the enterprise by considering the factors that caused the crisis or even bankruptcy. The management of financial crises was constrained by the insufficient development of the informational-methodical base in this direction. In this context, not only the local experience but also the global one showed that the use of crisis management is quite difficult from a practical point of view, respectively, it requires an improvement and development in methodological-methodological terms, which requires evaluation of meticulous crises at the enterprise, which allows the diagnosis and prediction of crises with higher accuracy at each stage of its development.
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Liston, Katie, Rustom P. Manecksha, and Conor P. Woods. "Hyperglycaemic crisis secondary to emphysematous pyelonephritis." BMJ Case Reports 14, no. 8 (August 2021): e242617. http://dx.doi.org/10.1136/bcr-2021-242617.
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A 49-year-old woman presented to the emergency department acutely unwell. Initial investigations revealed hyperglycaemia, ketosis and an acute kidney injury precipitated by urosepsis. She was found to have a new diagnosis of diabetes mellitus (type 2) with a glycated haemoglobin (HbA1c) of 156 mmol/mol. CT imaging of the abdomen and pelvis revealed unilateral emphysematous pyelonephritis (EPN), radiologically classified as stage 3 severity with gas extending beyond the renal collecting system. Escherichia coli was grown on blood and urine cultures. This was sensitive to second-generation cephalosporin cefuroxime. The patient was managed with fluid resuscitation, intravenous antibiotics and renal system decompression with urinary catheter insertion. She was commenced on an intravenous insulin infusion for hyperglycaemic crisis. This case illustrates a rare presentation of hyperglycaemic crisis precipitated by EPN in a patient without a previously known diagnosis of diabetes, successfully treated with medical management alone. Close clinical and radiological follow-up was arranged to monitor the need for future nephrectomy.
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Batal, Ibrahim, Robyn T. Domsic, Thomas A. Medsger, and Sheldon Bastacky. "Scleroderma Renal Crisis: A Pathology Perspective." International Journal of Rheumatology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/543704.
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Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is associated with increased vascular permeability, activation of coagulation cascade, and renin secretion, which may lead to the acute renal failure typically associated with accelerated hypertension. The histologic picture of SRC is that of a thrombotic microangiopathy process with prominent small vessel involvement manifesting as myxoid intimal changes, thrombi, onion skin lesions, and/or fibrointimal sclerosis. Renal biopsies play an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in SSc patients, helping to predict the clinical outcome and optimizing patient management. Kidney transplantation may be the only treatment option available for a subset of SRC patients who develop end-stage renal failure despite aggressive angiotensin-converting enzyme inhibitor therapy. However, the posttransplant outcome for SSc patients is currently suboptimal compared to the general renal transplant population.
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Islam, Fahmida, Wahiduzzaman Mazumder, ASM Bazlul Karim, Subir Ananda Biswas, Rafia Rashid, Mohammad Shariful Hasan, and Fahmida Begum. "Tyrosinemia Type 1 – A case report." Bangladesh Journal of Child Health 43, no. 3 (October 7, 2020): 174–76. http://dx.doi.org/10.3329/bjch.v43i3.49577.
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Tyrosinemia Type 1 is a rare inherited metabolic disorder attributable to a deficiency of enzyme fumaryl acetoacetate hydrolase. It has an autosomal recessive pattern of inheritance. It often presents with liver disease or liver failure with predominant bleeding tendencies, Fanconi syndrome and or rickets with neurological crisis. Diagnosis is based on clinical features, increased tyrosine and methionine in plasma and the presence of succinylacetone in urine. Untreated patient develops liver failure, cirrhosis and hepatocellular carcinoma and end stage of renal failure. Here we describe a 9 months old infant presented with massive ascites with hepatosplenomegaly, coagulopathy and hypoalbuminemia. The diagnosis of tyrosinemia type 1 was confirmed based on clinical and biochemical findings. We highlight the need for early diagnosis and initiating treatment at the earliest which improves the quality of life in these patients. Here we report a nine month old male infant presented with abdominal distension, hepatomegaly and ascities diagnosed as Tyrosinemia Type 1.
Bangladesh J Child Health 2019; VOL 43 (3) :174-176
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Takemoto, Tina. "LOVE/SICK: A CONVERSATION WITH ANGELA ELLSWORTH." Theatre Survey 53, no. 1 (April 2012): 105–14. http://dx.doi.org/10.1017/s0040557411000974.
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Editor's Note: In this previously unpublished conversation from 2007, Tina Takemoto and Angela Ellsworth discuss their collaboration during a period when Ellsworth was diagnosed with and underwent treatment for Hodgkin's lymphoma. For those compelling collaborations, the artists confronted the effects of diagnosis and prognosis on the experience of embodiment, the gendered and racialized practices of medical care, and the limits of empathy in communicating across illness/health. In this conversation, Takemoto and Ellsworth reconvene after a crisis in their collaborations to work through the complications that arose for each in their attempts to stage and manage performances that would make a difference in the treatment of cancer. This interview was conducted in New York City on 16 September 2007.
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Saroyo, Yudianto Budi, Achmad Kemal Harzif, Beryliana Maya Anisa, and Fistyanisa Elya Charilda. "Thyroid storm in the second stage of labour: a case report." BMJ Case Reports 14, no. 7 (July 2021): e243159. http://dx.doi.org/10.1136/bcr-2021-243159.
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A thyroid storm (or thyroid crisis) is an emergency in endocrinology. It is a form of complication of hyperthyroidism that can be life-threatening. Inadequate control of hyperthyroidism in pregnancy could develop into thyroid storm, especially in the peripartum period. We present a woman came in the second stage of labour, with thyroid storm, superimposed pre-eclampsia, acute lung oedema and impending respiratory failure. Treatment for thyroid storm, pre-eclampsia protocol and corticosteroid was delivered. The baby was born uneventfully, while the mother was discharged after 5 days of hospitalisation. Delivery is an important precipitant in the development of thyroid storm in uncontrolled hyperthyroidism in pregnancy. Although very rare, it can cause severe consequences. Diagnosis and treatment guidelines for thyroid storm were available and should be done aggressively and immediately. Uncontrolled hyperthyroidism should be prevented by adequate control in thyroid hormone levels, especially before the peripartum period.
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Verovšek, Peter J. "Social criticism as medical diagnosis? On the role of social pathology and crisis within critical theory." Thesis Eleven 155, no. 1 (November 20, 2019): 109–26. http://dx.doi.org/10.1177/0725513619888663.
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The critical theory of the Frankfurt School starts with an explanatory-diagnostic analysis of the social pathologies of the present followed by anticipatory-utopian reflection on possible treatments for these disorders. This approach draws extensively on parallels to medicine. I argue that the ideas of social pathology and crisis that pervade the methodological writings of the Frankfurt School help to explain critical theory’s contention that the object of critique identifies itself when social institutions cease to function smoothly. However, in reflecting on the role that reason and self-awareness play in the second stage of social criticism, I contend that this model is actually better conceptualized through the lens of the psychoanalyst rather than the physician. Although the first generation’s explicit commitment to psychoanalysis has dissipated in recent critical theory, faith in a rationalized ‘talking cure’ leading to greater self-awareness of existing pathologies remains at the core of the Frankfurt School.
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Tkhatl, L. K., T. V. Stavenchuk, E. D. Kosmachova, and I. A. Pashkova. "Criteria for diagnosis of humoral rejection using the method of 2D-speckle-tracking echocardiography." Russian Journal of Transplantology and Artificial Organs 21, no. 1 (May 18, 2019): 46–56. http://dx.doi.org/10.15825/1995-1191-2019-1-46-56.
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Aim: to identify predictors of humoral rejection at different stages using non-invasive methods of 2D-speckletracking echocardiography, to determine the correlation with immunological changes.Materials and methods. The study was conducted on the basis of Regional Clinic Hospital of Krasnodar from 2010 to 2017. The analysis of 181 heart recipients was performed. 5 groups were allocated due to the crisis of humoral rejection and the identified antibodies to donor leukocyte antigens (HLA antibodies): group 1 (n = 10) – DSA and humoral rejection, group 2 (n = 7), patients with non-DSA and humoral rejection, group 3 (n = 17) – patients with antibodies to HLA, no humoral rejection, group 4 (n = 11), humoral crisis of rejection, with no identified HLA antibodies, group 5 (n = 87) – patients do not have antibodies to HLA and signs of both humoral and cellular rejection according to EMB. Recipients were carried out endomyocardial biopsy, immunological study, 2D-speckle-tracking echocardiography, statistical methods.Results. The diagnostic criteria for a humoral rejection is greater than 1 degree are global peak systolic strain or strain rate of left ventricle (GLPSLV) – 9.94 ± 1.37% (the sensitivity was 86.2%, specificity – 90.4%); radial systolic strain (RadSLV) of 19.36 ± 3.66% (sensitivity was 75.8%, specificity – 84.5%); circumferential systolic strain (CiRSLV) – 17.83 ± 4.79% (sensitivity was 78.6%, specificity – 84.4%); the twisting of the left ventricle (twist) – 8.90 ± 1.85% (sensitivity – 66.7%, specificity – 94.2%), p < 0.001. When considering indicators GLPSLV and longitudinal peak strain of the right ventricle (GLPSRV) in the diagnosis of humoral rejection sensitivity increases to 91.9%, specificity increases to 94.6%, p < 0.001.Conclusion. GLPSLV has greater sensitivity at the stage of subclinical changes. It is more significantly reduced with increasing degree of rejection associated with episodes of rejection in comparison with other parameters and deformation mechanics. The interrelation between histological and immunological changes and impaired myocardial deformation. The proposed diagnostic algorithm will predict humoral rejection.
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Runciman, W. B., R. K. Webb, I. D. Klepper, R. Lee, J. A. Williamson, and L. Barker. "Crisis Management—Validation of an Algorithm by Analysis of 2000 Incident Reports." Anaesthesia and Intensive Care 21, no. 5 (October 1993): 579–92. http://dx.doi.org/10.1177/0310057x9302100515.
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Anaesthetists are called upon to manage complex life-threatening crises at a moment's notice. As there is evidence that this may require cognitive tasking beyond the information-processing capacity of the human brain, it was decided to try and develop a generic crisis management algorithm analogous to the “Phase I” immediate response routine used by airline pilots. Such an algorithm, based on the mnemonic “COVER ABCD, A SWIFT CHECK”, was developed and refined over 3 meetings, each attended by 60–100 anaesthetists and aviation psychologists. It was validated against 1301 relevant incidents among the first 2000 incidents reported to the Australian Incident Monitoring Study. It proved sufficiently robust and safe to recommend its general use as an initial response to any incident or crisis which occurs when a patient is breathing gas from an anaesthetic machine. It requires a limited knowledge base and is easily learnt and rehearsed during the anaesthetist's working day. It will provide a functional diagnosis in over 99% of cases and will correct 62% of the problems in 40–60 seconds. In the remaining 37% it will allow the anaesthetist to proceed with a “sub-algorithm”, confident in the knowledge that some important step has not been missed. In just over 30% of incidents this will be for a problem familiar to all anaesthetists (e.g. laryngospasm, bradycardia); in just over 6% it will be for a less common, more complex, but finite, set of problems (3% cardiac arrest, 1% air embolism, 1% anaphylaxis, 1% for the remaining desaturations); in less than 1% diagnosis and correction will require a more complex checklist (e.g. for malignant hyperthermia, pneumothorax). The next stage, the development of specific sub-algorithms and a structured team approach for ongoing problems, is in progress.
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Savchenko, Maryna, and Olga Shkurenko. "FORMATION OF THE MECHANISM OF ANTI-CRISIS MANAGEMENT BY INTERNATIONAL ENTITIES." Economic Analysis, no. 30(4) (2020): 74–83. http://dx.doi.org/10.35774/econa2020.04.074.
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Introduction. The objective pattern of development of any socio-economic system is cyclical, which includes the crisis phase. This phase is especially evident in the current conditions of functioning of international business entities in various fields and industries. A review of scientific publications has demonstrated the fragmentary nature of research on the formation of an anti-crisis mechanism for managing international business entities. That is why the problem of studying the possibilities of survival in the economic crisis and the application of an effective mechanism of crisis management is one of the most pressing today. Purpose. The purpose of the article is to develop theoretical and methodological provisions for improving the substantive characteristics of the mechanism of crisis management of international business entities. Method (methodology). The article uses a number of general scientific research methods, including monographic method, methods of scientific abstraction and generalization, dialectical method, induction and deduction provided gradual refinement of structural elements of the mechanism of crisis management in modern conditions. Results. It is proved that the crisis is derived from the cyclical nature of the reserves of the economy, which on the one hand causes a real threat of bankruptcy for international businesses in a period of declining production, and on the other - is an objective prerequisite for their further growth and development. The periods of development of the crisis of the subjects of international business are formed and the managerial, financial and economic-legal crisis are singled out accordingly. The article proposes to understand the crisis of international business entities as a set of situations caused by exogenous and endogenous factors that upset the balance of the international business entity, and over time may lead to changes in organizational, economic and production mechanism of its operation. The authors of the article build a mechanism of anti-crisis management of international business entities, which is a set of elements, technologies and tools that provide prediction of crisis danger, symptom analysis, and identify measures to reduce the negative effects of the crisis for international business entities and the use of factors for their further development. The constituent elements of the mechanism of anti-crisis management of international business entities are grouped into six blocks: crisis diagnosis; selection and substantiation of influencing factors to determine the signs of crisis; determination of the phase (stage) of the life cycle of an international business entity; determining the type of crisis management; selection and substantiation of indicators for crisis diagnosis; implementation of crisis management. The proposed mechanism allows to bring international business entities out of crisis situations and ensure the stabilization of their financial condition.
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Leliuk, D. V. "HEART RATE VARIABILITY INDICATORS, AS PREDICTORS OF THE ADVERSE COURSE OF UNCOMPLICATED HYPERTENSIVE CRISIS." Modern medical technologies 44, no. 1 (March 1, 2020): 41–47. http://dx.doi.org/10.34287/mmt.1(44).2020.6.
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Abstract Purpose of the study. Improve the outcomes of treatment for uncomplicated hypertensive crises at the prehospital stage by studying the state of systemic hemodynamic, determining the balance of the autonomic nervous system and markers associated with the systemic inflammatory response in arterial hypertension patients in uncomplicated cases of hypertensive crisis. Materials and methods. During the 2017–2019 period, an open, prospective and comparative study was conducted and consisted of 206 patients with documented second-stage hypertension, of which 131 patients sought emergency medical attention in the «Municipal Institution Zaporizhzhya Station of Emergency (Ambulance) Medical Assistance» and 75 people who had a stable course of the disease and were examined on an out patiently on the basis of the «Primary health care Centre No 10». Practically healthy 31 people were examined on the basis of the MI «Regional medical exercises dispensary». The indices of heart rate variability in the examined persons were analyzed. All patients were examined physically, used generally clinical, instrumental and laboratory methods for ECG diagnosis were recorded according to the standard method, on a 12-channel computer-cardiographic complex «Cardiolab» (KhAI-Medika, Kharkov). The examinations were performed before the start of emergency care and after HC relief. For the analysis of heart rate variability, a 5-minute ECG interval recorded at rest was used, and the signal was recorded in the supine position, with calm breathing. The obtained data were analyzed with the help of the Cardiolab-HRV software complex, followed by the analysis of the cardiorhythmogram according to the generally accepted method. Results. The analysis of the obtained evidence showed that the total HRV (by all indicators was significantly reduced in patients with hypertonic disease compared with healthy individuals), and with the development of hypertensive crisis in patients with hypertonic disease was even lower. In the hypertonic disease group with hypertensive crisis, activation of the sympathetic division of the autonomic nervous system (with increasing LF/HF ratio) was detected, but despite a higher LF/HF index of 2,21 (0,86–3,94) there was no significant difference against level 1,85 (1,56–2,03) in the hypertonic disease group without hypertensive crisis and a value of 1,81 (1,66–1,89) among healthy persons (p > 0,05). Conclusions. The results obtained indicate that the decrease in compensatory capacity in all HRV indicators is more pronounced in patients with hypertonic disease in the development of hypertensive crisis. Assessment of heart rate variability indicators may be a useful component of cardiovascular risk stratification, requiring further statistical analysis. Keywords: hypertension, uncomplicated hypertensive crisis, heart rate variability.
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Vásquez Abanto, J. E., A. E. Vásquez Abanto, and S. B. Arellano Vásquez. "Clinical bases of the syndrome of hypertensive crisis in the primary care." EMERGENCY MEDICINE 17, no. 1 (April 14, 2021): 72–88. http://dx.doi.org/10.22141/2224-0586.17.1.2021.225725.
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Hypertensive crisis is a common occurrence at the level of all primary healthcare. One of the main tasks in the diagnosis and treatment of a hypertensive crisis in emergency medicine is the ability to differentiate between a hypertensive emergency and urgency, based on the presence of damage to the target organ in the first case. An appropriate stratification, prevention, and regression of the damage caused by hypertensive crisis could prevent future events in the long term. The states of hypertensive urgency (uncomplicated hypertensive crisis) are usually not associated with an immediate risk to life, so treatment can be started, even completed, on an outpatient basis. Hypertensive emergency conditions (complicated hypertensive crisis) are very serious clinical situations that require hospitalization. In a case of severe hypertension in a patient, asymptomatic or with non-specific symptoms, a cautious therapeutic approach should be taken. When treating conditions of hypertensive urgency, the efforts of physicians are aimed both at lowering blood pressure (at least 20 % of the baseline) and avoiding its sudden and/or excessive decrease (it is necessary to maintain penumbra zone). Therefore, fast-acting drugs should not be used because of the risk of ischemic events. In the case of hypertensive emergency conditions, the choice of drugs should be individual, and the parenteral route of administration is the most common form. In the absence of symptoms of target organ damage, most of the patients are likely to be treated on an outpatient basis. Compliance with a clear continuity of diagnostic and therapeutic measures at the prehospital stage and in the hospital is a necessary condition for the real stabilization of this state. Emergency conditions associated with a hypertensive crisis are the main reasons for contacting and/or calling the physician of emergency medicine in Ukraine (≈ 25–26 %). Hypertensive crisis, the primary manifestation or complication of a previously diagnosed arterial hypertension, most often can occur as a severe increase in blood pressure ≥ 180/120 mm Hg (although the clinical picture of hypertensive crisis is sometimes observed with lower numbers). The literature search methods are as follows Scopus database, Web of Science, MedLine, CyberLeninka, RISC.
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Guilhot, François, John Coombs, Tomasz Szczudlo, Oleg Zernovak, Nancy J. Macdonald, and Ari Shapiro. "An Ethnographic Investigation Tracking the Experience of Chronic Myeloid Leukemia (CML) Patients on Tyrosine Kinase Inhibitor (TKI) Therapies." Blood 116, no. 21 (November 19, 2010): 394. http://dx.doi.org/10.1182/blood.v116.21.394.394.
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Abstract Abstract 394 Background: The advent and approval of TKIs has dramatically improved the life expectancy of patients with CML. As treatment innovation has transformed CML into a chronically managed disease, we examined the impact of these changes on patients with CML in order to offer recommendations for healthcare providers (HCPs) to better support patients with CML. Method: 50 patients with CML from Brazil, France, Germany, Russia and Spain were included in this ethnographic investigation including: patients within 18 months of diagnosis and on frontline imatinib therapy (n = 20), patients with ongoing frontline treatment (> 18 months to 7 years, n = 20), and patients who were switched to second- or third-line TKI therapies (n = 10). Patients in all 5 countries participated in a 2.5-hour in-home interview, and patients in Brazil and France completed 7-day photo journals and an optional telephone debrief interview. Patients were asked to discuss and write about their perceptions and experiences regarding such issues as adherence, disease knowledge, disease management, and their relationship with HCPs. Result: This global ethnographic investigation generated a 5-stage, patient-centered model emphasizing emotions and experiences throughout the diagnosis, treatment and management of their disease: crisis, hope, adaption, normalcy, and uncertainty. Depending upon their circumstances, these experiential stages were found to be abbreviated or prolonged and influenced by patients having differentiating levels of knowledge about their disease, comfort levels with the treatment and/or their HCPs, as well as different degrees of optimism about their treatment and long-term prognosis. In addition, the study results showed that patients cycle through the various stages of the model throughout the course of their disease. The crisis phase occurred at diagnosis and tended to resolve upon HCP reassurance of the availability of successful treatments. Hope followed crisis when patients were educated about their disease and its treatments and responded to initial therapy. Adaption involved patients adjusting to any physical changes wrought by the disease, treatments, and associated adverse events. As well, they began to psychologically come to terms with the long-term nature of their disease and develop their drug-taking routines and compliance pattern. As patients attained stability in their disease and adapted to changes, a ‘new’ normal returned and patients began to refocus their life away from the disease back to social, work, and family matters. The uncertainty stage was found to be associated with drug resistance, disease progression, newly occurring adverse events, or due to limitations around access to therapy because of public health regulations or personal financial issues. While uncertainty arose for multiple reasons and could occur at any time after patients had advanced through the 4 preceding phases, patients who went through stages of uncertainty most often cycled back to phases of adaption or normalcy once the issues were resolved. Conclusions: Here, we have identified 5 common patient experience stages and we provide recommendations based on patient research for the management of CML. This investigation suggests that HCPs can help patients move through the early stages of crisis and hope by providing reassurance, along with information and resources regarding drug efficacy and product differentiation, while explaining the importance of speed and depth of responses. Once in the adaption/normalcy stages, HCPs should set expectations for the risk/benefits of long-term chronic drug therapy and long-term disease monitoring and continue to support patient compliance and adherence programs while helping patients achieve and maintain a normal lifestyle. Disclosures: Guilhot: Novartis: Equity Ownership, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Coombs:Novartis: Employment, Equity Ownership. Szczudlo:Novartis: Employment, Equity Ownership. Zernovak:Novartis: Employment, Equity Ownership. Macdonald:Novartis: Consultancy. Shapiro:Novartis: Consultancy.
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Sophie, Elands, and Ingle Gordon. "THUR 216 Myasthenia gravis, thymoma and good’s syndrome." Journal of Neurology, Neurosurgery & Psychiatry 89, no. 10 (September 13, 2018): A31.1—A31. http://dx.doi.org/10.1136/jnnp-2018-abn.107.
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Myasthenia gravis (MG) is in 15% of cases a paraneoplastic phenomenon secondary to a thymoma. A subset of these will have both a thymoma and associated immunodeficiency known as Good’s syndrome. Immunological features include hypogammaglobulinaemia, a reduction in peripheral B cells, CD4+ lymphopenia, and reversal of CD4/CD8 ratio.We present two cases followed by a literature review:52 year–old man presented with dysphagia, diagnosed as MG. He was found to have a stage 4a thymoma (histology B2), subsequently resected. He was noted to have a reduction in peripheral B cells and CD4+ lymphopenia suggestive of Good’s syndrome. He has also had chronic diarrhoea and recurrent pulmonary infections with Pseudomonas, Klebsiella and Mycobacterium abscessus. Current immunotherapy includes prednisolone.42 year–old woman presented with a myasthenic crisis requiring ITU admission. She was found to have a thymoma (histology B3), treated with resection and adjuvant radiotherapy. Peripheral B cell reduction led to a diagnosis of Good’s syndrome. She is currently in remission on prednisolone, mycophenolate mofetil and 6–weekly immunoglobulin infusions.These cases illustrate that Good’s syndrome is an important differential when managing patients with myasthenia gravis, especially as the immunodeficiency may precede or occur after the diagnosis of a thymoma.
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Paprocki, Rafał. "Attitudes Towards COVID-19 Pandemic. Culture as Behavioral Driver under Risk and Uncertainty." Pomiary Automatyka Robotyka 24, no. 4 (December 30, 2020): 41–46. http://dx.doi.org/10.14313/par_238/41.
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The article deals with the issues of cultural determinants of decisions under risk and uncertainty, with emphasis on consumer behavior during the COVID-19 pandemic. The analysis of the crisis response has been based on D. Kahneman’s prospect theory, which was used to compare social behaviors in Poland, Italy, Great Britain and Singapore at an early stage of the pandemic. The main purpose of the considerations is to present the scale and level of impact of cultural determinants on national survival and security strategies against the COVID-19 crisis. The analysis and diagnosis of national survival strategies facilitates creation of products in accordance with behavioral and cultural determinants of consumer attitudes and preferences. In addition, the article presents some automatic systems supporting personnel management during the COVID-19 pandemic. Contemporary technological solutions monitoring employee behavior in the working environment can be implemented to increase the level of mental well-being and sanitary safety.
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ARTAMONOVA, Nataliia. "Economic and legal support for the process of bankruptcy prevention and liquidation of business entities." Economics. Finances. Law, no. 2/1 (February 26, 2021): 9–12. http://dx.doi.org/10.37634/efp.2021.2(1).2.
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Introduction. One of the most important indicators of the country's economic development is the level of growth in the number of financially insolvent, bankrupt and liquidated enterprises, because the interests of the state, business and the individual are in the zone of influence and attention. The purpose of the paper is to assess the legal changes in the legislation of Ukraine on the application of bankruptcy procedures and presents the economic justification and methodical implementation of a set of tools for timely detection of insolvency, their current and future assessment to prevent bankruptcy and liquidation of business entities. Results. The data of the State Statistics Service on the increase in the number of insolvent enterprises in 2020 are presented. The systematization of methods and tools for timely detection of insolvency in the context of legal innovations is proposed, thanks to the introduction of tools for testing, labeling, ranking. The testing program for early diagnosis of bankruptcy provides for the calculation of indicators to assess the structure of the balance sheet; opportunities to restore solvency and the ability to neutralize the threat of bankruptcy due to the internal potential of the enterprise. The system of markers and indicators is used to determine the creditworthiness of the enterprise and for self-analysis, when considering alternative sources of financing to avoid the threat of bankruptcy. Rating is used to definitively determine the level of financial stability or insolvency of the enterprise. Conclusion. This tools should be used at different stages: both at the pre-crisis stage, to prevent the possibility of financial deterioration, and at the crisis and post-crisis stages, to assess the effectiveness of the enterprise and the likelihood of early detection of bankruptcy.
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Kokoreva, Oksana I., Svetlana N. Bashinova, and Irina V. Taraskina. "Correction of Negative Manifestations in 3-year-old Children in Kindergarten Conditions." Humanitarian: actual problems of the humanities and education 22, no. 2 (March 31, 2022): 97–106. http://dx.doi.org/10.15507/2078-9823.057.022.202201.097-106.
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Introduction. The early age is an important and very difficult stage in the development of a person’s personality. The problem of overcoming negative manifestations during the crisis of three years seems to be particularly relevant, because at this stage the formation of consciousness and the position of the child’s personality takes place. The absence of special conditions for upbringing and communication with the child, taking into account age characteristics and contributing to the smooth course of the restructuring of the psyche, can lead to irreversible consequences that affect the development of personality in the future. Various ways and options for overcoming the crisis of three years were considered by domestic and foreign teachers and psychologists: L. S. Vygotsky, A. N. Leontiev, L. I. Bozhovich, D. B. Elkonin, E. Erickson, G. Bronson, S. Wolf, T. V. Guskova, M. G. Elagina, T. E. Dragunova, M. I. Lisina, A. Clark, N. A. Menchinskaya, V. S. Mukhina, J. Rusek, L. White, E. Koehler. Among the conditions for successfully overcoming the crisis, they call taking into account the new needs of a child, respect for the child’s personality by adults and a tactful attitude towards him or her, especially in conflict emotionally stressful situations, abandoning the desire to tame the child, giving him reasonable opportunities to demonstrate his/her independence, removing situations that lead a child to stress and aggravation of relationships with others. However, in most cases, recommendations on how to achieve this are general and relate to the upbringing of a child in the family. The analysis of the proposed ways to overcome the negative manifestations of the crisis of three years has shown that they do not provide sufficient characteristics of the psychological and pedagogical conditions necessary for the evolutionary development of personality at this age stage. They do not have a complete picture of the psychological and pedagogical effects on a child, they do not consider the role of a kindergarten teacher and the possibilities of a pre-school educational organization in overcoming this crisis, although a significant number of pre-school children currently attend kindergartens. Therefore, it became necessary to consider the possibilities of reducing the negative symptoms of the crisis of three years from the designated points of view. Materials and Methods. Theoretical analysis of literature, analysis of the state of practice, generalization of empirically obtained data, observation, conversation, experiment, mathematical methods of data processing. Results. Pronounced symptoms of the crisis were observed in 59 % of children, among them self-will was diagnosed in 67 %, stubbornness in 63 %, negativism in 46 %, despotism in 33 %, depreciation in 29 % of children. Situational manifestations of symptoms are present in 44 %, frequent – in 22 % of them. The most common cause of negative behavioral reactions of three-year-old is improper influence on the part of adults who do not want to take into account the needs and capabilities of a child changing with age and preventing the manifestation of independence of children. The focus of negative manifestations on adults was 67 %. Discussion and Conclusion. The most effective way to overcome the negative manifestations of the crisis of three years will be under the conditions of creating a developing environment aimed at reducing the negative reactions of the child and ensuring a positive emotional background of interaction with adults and peers; timely diagnosis of manifestations of negative behavioral reactions indicating the presence of crisis symptoms, in order to reduce their external and internal effects on the development of the child’s personality as a whole; regular special conversations with the child aimed at forming a positive level of relationships with adults and peers; creating playful ways of interacting with a child of early preschool age; mutual cooperation with parents to implement the principle of continuity of the educational process to reduce the negative manifestations of the symptoms of the crisis of three years.
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Brenes-Alfaro, Laura María, Dulce Rodríguez-Rodríguez, and Carlos Quesada-Acuña. "Implementación de una estrategia de comunicación para posicionar las buenas prácticas agrícolas (BPA): el caso de los productores de piña de la zona norte de Costa Rica/ Implementation of a communication strategy to adopt good agricultural practices (GAP)." Revista Internacional de Relaciones Públicas 11, no. 22 (December 23, 2021): 49–74. http://dx.doi.org/10.5783/rirp-22-2021-04-49-74.
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Based on the high use of agrochemicals and pressure on ecosystems from agricultural production, as well as complaints and social movements against pineapple crop in the northern region of Costa Rica, a communication strategy was articulated within the framework of the project “Characterization of agricultural practices and the use and management of agrochemicals in pineapple crop, for implementing good agricultural practices (GAP)”. The strategy focused on promoting agricultural and environmental education to help farmers in the implementation of GAPs in the northern region of Costa Rica. There are not many public relations studies about agriculture and rural areas in Latin America. However, public relations can contribute to community development, based on the search for relationships based on trust, mutual understanding, cooperation and a sense of belonging that could lay the foundations for promoting sustainable development. The methodology was carried out in three main stages: diagnosis, approach and execution, and evaluation of the strategy. In the initial stage, one of the main findings was the outstanding negativity in local and national media coverage of pineapple production. Based on the results of the diagnosis, four main problems to be addressed during the implementation stage were identified: 1) overdose of pesticides; 2) bad stubble management; 3) poor soil management; 4) disrespect for aquifer protection zones. For the second stage, we applied two tactics consisting of a set of tasks intended to target audiences identified as main or primary. Also, a training program and crisis management activities were executed. The final stage consisted of the application of an evaluation questionnaire to 25 farmers participating in the training program. The results were several activities developed in the communities, including a series of informative and educational products (videos, key messages through WhatsApp, newsletters, infographics, a guide for the identification of pests and diseases in the pineapple crop); press management; workshops at local schools; and a GAPs Fair to promote the sustainable production of pineapple. The strategy promoted a training program, consisting of 34 talks, which was attended by 240 people: farmers, university students, agricultural products and tools sales personnel, people from cooperatives and interested members of the public. According to the final evaluation, 68 % of the training participants stated that their ability to produce pineapple using GAP improved during the last years; 40 % stated that environmental balance was the main benefit of implementing GAPs in pineapple crop, followed by economic savings (24 %). This shows that the message related to the environment was the prevailing one, consistent with the environmental and educational communication proposed by the strategy. As a conclusion, of the three most implemented agricultural practices by pineapple farmers, we identified that two were part of those promoted by the communication campaign. Thus, the project’s communication strategy had a strong incidence in the improvement of agricultural practices in the area and increased the number of positive notes related to the pineapple crop, before the crisis. We were able to impact the local production of pineapple through a clearly established strategy. Also, this allowed us to face the different phases of the crisis situation.
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Ferrer, A., D. López, M. Vidal, M. Tobeña, S. Serrano, I. Pajares, E. Millastre, M. Ruiz-Echarri, J. Lambea, and A. Tres. "Evaluation of neurological symptoms in oncologic patients at the emergency department." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20728-e20728. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20728.
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e20728 Background: Neurological symptoms in cancer patients are common and some of them represent a potentially serious situation. They are a frequent cause of complaint at the Emergency Department (ED). The aim of the study is to describe the profile of cancer patient who consult at ED for neurological symptoms, their diagnosis and management. Methods: From October 2007 to October 2008, all cancer patients treated at the ED of our hospital were prospectively collected. The reasons for consultation, diagnosis and clinical management are described. Results: A total of 560 cancer patients were enrolled. Of them, 61 patients (11%) consulted for a neurologic symptom: 50 of these patients (82%) were stage IV disease and 30 (49,2%) were receiving chemotherapy treatment. Of the total of patients, 14 (23%) had lung cancer; 10 patients (16%) had colorectal cancer; and 8 patients (13%) had primary central nervous system tumor. Most frequent causes of complaint were: low level of consciousness, 13 patients (21%); mobility deficit, 12 patients (19%); syncope, 9 patients (15%) and comitial crisis, 6 patients (10%). Of the patients who consulted for a neurological symptom, 52% of cases (32 patients) the cause was a structural lesion of central nervous system. Tumor progression was the diagnosis made in 27 patients (44,3%), in 14 patients (23%) the diagnosis was a metabolic alteration. A 69% of patients (42 patients) required hospitalization, 26% was discharged (16 patients) and 5% (3 patients) needed to be under observation during at least 24 hours. Conclusions: Neurological symptom is a frequent cause of complaint at ED for cancer patients. especially in patients in advanced stages. The most frequent diagnosis made because of these symptoms is tumor progression. Metabolic alterations are also an important diagnosis because of their frequency and because they can be solved by medical treatment. Most patients who consult for neurological symptoms need hospitalization. No significant financial relationships to disclose.
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Cunquero-Tomás, Alberto J., Claudio D. Ávila-Andrade, Javier Milara, Karla Javier, Vega Iranzo, and Carlos Camps. "Safe neoadjuvant trastuzumab-based treatment in HER2 + inflammatory early breast cancer in a glucose 6-phosphate dehydrogenase-deficient postmenopausal woman: A case report and review of the literature." Journal of Oncology Pharmacy Practice 26, no. 2 (July 1, 2019): 492–95. http://dx.doi.org/10.1177/1078155219858173.
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Introduction Glucose 6-phosphate dehydrogenase (G6PD) is a basic antioxidant pathway for erythrocytes, being its deficiency the most common gene mutation worldwide. As breast cancer is one of the most frequent tumors, many of these patients may present with G6PD deficiency prior treatment without notice. Case report We present the case of a woman deficient for G6PD with the diagnosis of Stage IIIB (cT4d cN1 cM0) HER2-enriched early breast cancer. Management and outcome The patient underwent neoadjuvance with trastuzumab and anthracycline-free chemotherapy, based on docetaxel (75 mg/m2, 120 mg) and carboplatin (AUC 5, 560 mg). She did not present hemolytic crisis and no blood transfusions were needed. She achieved a good pathologic response and completed one-year adjuvant trastuzumab without incidences. Discussion Although the role of HER2 and trastuzumab in oxidative stress is not yet completely understood, we suggest that trastuzumab may be a suitable agent for treatment in patients with HER2-enriched breast cancer in a non-oxidative chemotherapy scheme, with acceptable responses and no triggering hemolytic crisis.
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Carella, A. M., G. Beltrami, G. Pica, C. Ghiggi, D. Lovera, G. Cirmena, and A. Garuti. "Clarithromycin Enhances tyrosine Kinase Inhibitor – Induced Cell Death by Inhibition of Late Stage Autophagy in Patients with Chronic Myeloid Leukemia At Diagnosis or with Resistant Stage of Disease." Blood 120, no. 21 (November 16, 2012): 3777. http://dx.doi.org/10.1182/blood.v120.21.3777.3777.
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Abstract Abstract 3777 Recent laboratory studies have demonstrated that clarithromycin (CAM) is effective at increasing the sensitivity of chronic myeloid leukemia (CML) cells to tyrosine kinase inhibitors (TKIs). The mechanism of induction of cell death by CAM combined with TKI appears to be via inhibition of late stage autophagy inhibitor chloroquine. This is clearly demonstrated by an increase in LC3-II protein levels and a concomitant increase in cellular vacuole formation (L. Shafranek, T.P. Hughes, Leukemia & Lymphoma 2012, early online 1–4). On our protocol, approved by our Ethical Committee, we treated 8 CML patients. Four consecutive patients, with advanced CML, who were in all cases resistant to TKI alone, achieved remarkable responses to the combination of TKI and CAM (Table 1). According to this positive experience, we thought that the combination CAM + TKI could be employed upfront at diagnosis, in the attempt to increase a faster complete molecular remission. Until now we have treated four patients at diagnosis. The median age was 45 years (range, 40 – 52). Two patients had intermediate and 2 patients high Sokal/Euro risk (Table 2). Two patients received imatinib 400 mg/die and 2 patients nilotinib 600 mg/die. CAM was given at a dose of 500 mg b.i.d. when the patients reached <20×109/L WBC after TKI alone. Since TKIs can inhibit CYP3A3, all patients were evaluated weekly for GOT/GPT/gGT, bilirubin, lipase, amylase; moreover imatinibemia or nilotinibemia were evaluated every 7–10 days. In case of the increase of TKIs value >1.000 ng/mL, we reduced the dose of CAM to 500 mg/die or we discontinued the drug if the value was >2.000 ng/mL. In six patients this combination did not result in liver, renal or cardiac toxicity. In two patients (one resistant and one at diagnosis) the TKI plasma levels reached values over 2.000 ng/mL and an increase of indirect bilirubinemia combined with amylase/lipase increase was achieved. We stop CAM and reduced TKIs with prompt renormalization of all values. With this adjustment the value of TKIs were maintained under 1.000 ng/mL. Three out four patients treated at diagnosis achieved CCyR and MMR at 3, 3, 6 months and 5, 10 and 12 months, respectively. No patient has gone off study for toxicity and in no case we observed grade 3–4 myelosuppression. The remarkable responses obtained in these patients support the hypothesis that inhibition of autophagy may make CML cells sensitive to killing by TKIs. Table 1. Clinical characteristics and responses to clarithromycin + TKI in resistant patients Age, sex Sokal/Euro Date of Diagnosis Previous therapy Best response Status at CAM start Best response after CAM + TKI 43, F High Risk 02/2000 INF-a/ARA-C Imatinib Nilotinib Dasatinib CHR PCyR Ph+ 100% bcr-abl/abl 6,1% CHR CCyR bcr-abl/abl 0,09% (d +81) 53, M Ly/BC-CML 08/2010 Chemio + Imatinib Allografting Dasatinib CHR CCyR bcr-abl/abl 143% under Dasatinib bcr-abl/abl 1,5% 68, M Intermediate Risk 10/1999 mini-ICE Autografting INF-a Imatinib Dasatinib CCyR Ph+ 100% bcr-abl/abl 42,5% bcr-abl/abl 0,0022% (d +37) 70, F High Risk 10/1998 INF-a/ARA-C Imatinib Nilotinib Dasatinib Omoharringot. +/− ARAC CHR CCyR Ph+ 100% bcr-abl/abl 140% E255V mutation bcr-abl/abl 0,09% (d +53) Ly/BCR-CML: Lymphoid blast crisis/CML d'emblee; CHR: Complete Hematologic Remission, CCyR: Complete Cytogenetic Remission; PCyR: Partial Cytogenetic Remission; MMR: Major Molecular Remission Table 2. Clinical characteristics and responses to clarithromycin + TKI at diagnosis in untreated patients Age, sex Sokal/Euro Therapy at diagnosis bcr-abl/abl at diagnosis bcr-abl/abl - best response after CAM + TKI 52, M Intermediate Risk Nilotinib 110,60% (nov-11) 0,07% (apr-12) (5 mo.) 40, M Intermediate Risk Nilotinib 69% (oct-11) 0,02% (jul-12) (10 mo.) 42, M High Risk Imatinib 178% (aug-11) 0,05% (aug-12) (12 mo.) 49, M High Risk Imatinib 90% (nov-11) 0,8% (jul-12) (9 mo.) Disclosures: No relevant conflicts of interest to declare.
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Oliveira, Fabio Morato, Ferdinando de Paula Silva, Ana Paula N. Rodrigues Alves, Belinda Pinto Simoes, Roberto P. Falcao, and Sabine Mai. "Three-Dimensional Nuclear Telomeric Organization (3D) of Chronic Myeloid Leukemia Patients Predicts Accelerated Phase and Blast Crisis." Blood 120, no. 21 (November 16, 2012): 2771. http://dx.doi.org/10.1182/blood.v120.21.2771.2771.
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Abstract Abstract 2771 One major cause of genomic instability and cellular apoptosis is telomere dysfunction. Telomere loss or dysfunction results in breakage–bridge –fusion cycles, aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells: nuclei of the latter tend to be disorganized and commonly contain telomeric aggregates. However, few studies have addressed the impact of telomeres dynamics in CML progression. The frequency of additional chromosomal abnormalities in CML is around 5% in chronic phase and increases to 50–80% in the advanced phases. Clonal evolution often precedes progression and is predictive for inferior therapeutic outcome. In order to better understand cellular and molecular mechanisms in CML progression, the objectives of this investigation were examine telomere dysfunction and alterations in the 3D nuclear telomere architecture. Eighteen CML patients, in total, 54 bone marrow samples (chronic phase, accelerated phase and blast crisis) were eligible for 3D nuclear telomeric investigation. The quantitative FISH (QFISH), cytologic diagnosis and the cytogenetic determination for additional chromosomal abnormalities were assessed according to standard protocols. 3D image analysis on 30 interphase nuclei per slide was obtained by using an Axio Imager A1 microscope (Carl Zeiss, USA). Sixty z-stacks were acquired at a sampling distance of x,y: 102 nm and z: 200 nm for each slice of the stack. AxioVision 4.8 software (Carl Zeiss, Canada) was used for 3D image acquisition, and deconvolution analysis. Three CML subgroups were defined on the basis of their 3D telomeric profiles. The telomeric parameters (number, length, telomere aggregates and nuclear volumes) were compared between these three subgroups. Distribution of telomere intensities in CML phases was compared between the patient's subgroups. All patients of a same subgroup displayed similar 3D telomeric profiles. Comparison with clinical diagnosis after the classification according to telomere profile showed that all CML patients were classified in the three distinct subgroups. Statistical analyses showed significant differences between the CML subgroups (P<0.001). Each of the quantitative telomere parameters exhibited significant differences. Furthermore, statistical analyses combining all 3D telomere parameters revealed significant differences between all subgroups (P<0.05). According to our data these profiles are correlated to the disease evolution and increased telomere dysfunction in these subgroups. It seems that the evolution of CML progresses from low to high level of telomere dysfunction, that is, from early stage to more aggressive stage, followed by disease transformation. We concluded that telomere 3D organization is a highly accurate tool to distinguish CML stages. We propose that monitoring 3D telomere dysfunction might be a very powerful marker to measure this transformation. Furthermore, it may be a better indicator of therapeutic response because an optimal response will lead to a normal cellular biology, including elimination of abnormal telomeric aggregates and the increase of normal 3D telomeric profiles. Financial support: FAPESP (2011/01647-2). Disclosures: No relevant conflicts of interest to declare.
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Heimes, Diana, Lena Katharina Müller, Alexandra Schellin, Hendrik Naujokat, Christian Graetz, Falk Schwendicke, Maximilian Goedecke, Benedicta Beck-Broichsitter, and Peer W. Kämmerer. "Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany." Cancers 13, no. 12 (June 9, 2021): 2892. http://dx.doi.org/10.3390/cancers13122892.
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(1) Background: In response to the global COVID-19 pandemic, governmental measures have been undertaken. The impact of the crisis on the healthcare of patients with cancer is largely unexplored. This multicenter cohort study aimed to investigate a potential screening delay and its consequences in patients with oral cancer (OC) during the pandemic. (2) Material and Methods: Data of patients who were first diagnosed with OC during different periods were collected, especially in terms of OC incidence, tumor stage/entity and time to intervention. The periods lockdown (LD) (13 March–16 June 2020), post-lockdown (PLD) (17 June–1 November 2020), and the corresponding equivalents in 2018/19 were differentiated and compared. (3) Results: There was no obvious trend towards a higher incidence of OC or higher tumor stages, whereas a trend towards a shorter time to intervention during the LD2020 could be observed. Subgroup analyses revealed an increased incidence in OC within the PLD2020 in Mainz, which might be explained by the partial closure of dental practices in this federal state during LD. (4) Conclusions: While there was no overall higher incidence of OC, we found closure of practices during LD to possibly delay cancer diagnosis. Therefore, measures must be taken to identify patients at risk and to ensure basic healthcare, especially in the context of dental screening measures.
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Krishnan, Vaidehi, Dennis Dong Hwan Kim, Timothy P. Hughes, Susan Branford, and S. Tiong Ong. "Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers." Haematologica 107, no. 2 (October 7, 2021): 358–70. http://dx.doi.org/10.3324/haematol.2021.279317.
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Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML.
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Chagpar, Anees B., Donald R. Lannin, Sarah Schellhorn Mougalian, Elizabeth Rapp Berger, Cary Philip Gross, Nina Ruth Horowitz, Tara B. Sanft, Michael DiGiovanna, Mehra Golshan, and Lajos Pusztai. "How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer?" Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e18708-e18708. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18708.
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e18708 Background: The COVID-19 pandemic has caused shifts in terms of cancer management, but the impact of this has not been well-elucidated in a contemporary cohort of patients in clinical practice in the US. We hypothesized that closure of operating rooms would increase the use of neoadjuvant therapy (NT) during the early pandemic period. Methods: The nationwide Flatiron Health database is a longitudinal electronic health record (EHR)-derived database, comprising de-identified, patient-level structured and unstructured data, curated via technology-enabled abstraction. These data originated from approximately 280 cancer clinics. We compared patients diagnosed with non-metastatic breast cancer during the early pandemic period (March 1 – June 30, 2020; group 1) with those diagnosed in the four month period prior (November 1, 2019 – February 29, 2020; group 2) and those diagnosed during the same period one year earlier (March 1 – June 30, 2019; group 3). Results: There were 174 patients in group 1, 277 in group 2, and 348 in group 3. Overall, 591 (74.1%) were ER/PR+HER2-, 100 (12.6%) were HER2+, and 106 (13.3%) were triple negative (TN). Patients in the three groups were equally likely to be ER/PR+HER2- (75.3% vs. 72.2% vs. 74.9%, p = 0.68), HER2+ (12.1% vs. 14.9% vs. 11%, p = 0.33), TN (12.6% vs. 12.7% vs. 14.2%, p = 0.83) and to be high risk by genomic testing (either Oncotype Dx or Mammaprint; p = 0.72). While there was no difference in the clinical stage (p = 0.36) nor patient age at diagnosis (p = 0.76) across the three groups, patients diagnosed during the early pandemic (group 1) were more likely to receive NT compared to those diagnosed one year earlier (group 3); 28.7% vs 16.4%, p < 0.01 (see table). The use of NT differed between the three groups in the ER/PR+her2- (p < 0.01) and her2+ patients (p = 0.05), but not in the TN patients (p = 0.61). There was no difference in the use of NT overall during the pandemic by geographic state (p = 0.32) nor practice setting (p = 0.23); NT was also similar by geographic state and practice setting when considering the ER/PR+HER2-, HER2+, and TNBC subsets. Conclusions: Despite similar clinicopathologic features as earlier time periods, there was an increased use of NT during the early pandemic when compared to the same period in the prior year. This was seen particularly in the ER/PR+HER2- group, suggesting an increased use of neoadjuvant endocrine therapy.[Table: see text]
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Guth, Amber Azniv, Brian Diskin, Freya Schnabel, Nakisa Pourkey, Deborah Axelrod, and Richard Shapiro. "Abstract P2-03-01: Changes in breast cancer presentation during Covid-19: Experience in an Urban Academic Center." Cancer Research 82, no. 4_Supplement (February 15, 2022): P2–03–01—P2–03–01. http://dx.doi.org/10.1158/1538-7445.sabcs21-p2-03-01.
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Abstract Background: The COVID-19 pandemic strained healthcare systems worldwide, delaying breast cancer screening and surgery. In 2019, approximately 80% of breast cancers in the U.S. were diagnosed on screening examinations, with 76.4% of eligible Medicare patients undergoing screening at least every two years. Since the start of the pandemic, many women have been reluctant to seek elective screening mammography, even with the lifting of “lock-down”. We describe the effect of the COVID-19 pandemic on breast cancer presentation at an academic medical center in a city hit hard by the pandemic. Materials and Methods: The institutional IRB-approved Breast Cancer Registry Database was queried for patients enrolled during two time periods, those undergoing first surgical procedure before the start of the pandemic (4/1/2019-3/31/2020) to those the year after the pandemic started (4/1/2020-3/31/2021). Elective cancer surgery was paused for 3 weeks, ending 4/20/2020, and access to routine breast care was limited for 3 months. Variables included age, method of detection, palpability, histologic subtype and staging, neoadjuvant systemic therapy, cancer specific treatments, and radiation uptake. Results: 349 patients were in the 2019 cohort; 246 in the 2020 cohort. No differences in baseline characteristics, including age at presentation, nodal status, or operation type. Fewer cancers were detected on routine mammography post-COVID vs. pre-COVID. Increase in detection of breast cancer through self-exams in 2020 was seen compared to 2019. Palpability on presentation also increased. More patients were treated with neo-adjuvant therapy chemotherapy, and 36 of 45 (80%) eligible early-stage breast cancer patients accepted neoadjuvant hormonal therapy during the period that elective cancer surgery was on hold. Patients received radiation therapy less frequently during the pandemic. The proportion of patients diagnosed with invasive ductal cancers was higher in the 2020 cohort and the proportion of patients diagnosed with ductal carcinoma in situ (DCIS) and for invasive lobular cancers (ILC) was lower. Conclusions: Patients at an academic New York City medical center presented with more palpable and invasive breast cancers during the COVID-19 pandemic compared to the preceding year, and fewer patients with DCIS and ILC, cancers typically detected following screening mammography. While stage migration with an increase in diagnosis of late stage cancers has been described, in our population the stage shift occurred in early stage breast cancer, with decreases in DCIS and increases in Stages I-II, with the higher stages III-IV essentially unchanged. This reflects the effect of delay in our previously highly-screened population, with an average screening delay of 3 + months, and many patients missing their yearly screening altogether. While many medical interactions during COVID-19 were via telemedicine, radiation therapy requires daily office visits, and fear of exposure contributed to the lower rate of radiation. Given the increase in invasiveness and stage of breast cancers diagnosed during the COVID-19 pandemic, this study emphasizes the importance of screening for diagnosis and treatment of breast cancer, even in the face of a concurrent health crisis. Variable2019 Population N=3492020 Population N=246P-ValueMethod of DetectionSelf-Exam19.80%26.0%0.0688Mammography67.0%60.0%Palpability31.50%39.20%0.0533Neoadjuvant Therapy8.30%10.20%0.4384Radiation Therapy65.0%54%<0.0001Age at presentation60.0460.680.6171Type of surgeryBreast Conserving Surgery69%66%<0.8508Mastectomy31%34%HistologyIDC60.70%66.7%0.5822DCIS20.9%16.7%ILC10.6%8.10% Citation Format: Amber Azniv Guth, Brian Diskin, Freya Schnabel, Nakisa Pourkey, Deborah Axelrod, Richard Shapiro. Changes in breast cancer presentation during Covid-19: Experience in an Urban Academic Center [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-03-01.
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Bai, Mei, Mark Lazenby, Sangchoon Jeon, Jane Dixon, and Ruth McCorkle. "Exploring the relationship between spiritual well-being and quality of life among patients newly diagnosed with advanced cancer." Palliative and Supportive Care 13, no. 4 (July 3, 2014): 927–35. http://dx.doi.org/10.1017/s1478951514000820.
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AbstractObjective:In our context, existential plight refers to heightened concerns about life and death when people are diagnosed with cancer. Although the duration of existential plight has been proposed to be approximately 100 days, evidence from longitudinal studies raises questions about whether the impact of a diagnosis of advanced cancer may require a longer period of adjustment. The purpose of our study was to examine spiritual well-being (SpWB) and quality of life (QoL) as well as their interrelationship in 52 patients with advanced cancer after 100 days since the diagnosis at one and three months post-baseline.Method:The study was designed as a secondary data analysis of a cluster randomized clinical trial involving patients with stage 3 or 4 cancer undergoing treatment. SpWB was measured using the 12-item Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale (FACIT–Sp–12); common factor analyses revealed a three-factor pattern on the FACIT–Sp–12. Quality of life was measured with the Functional Assessment of Cancer Therapy–General (FACT–G). We limited our sample to participants assigned to the control condition (n = 52).Results:SpWB and QoL remained stable between one and three months post-baseline, which were a median of 112 and 183 days after diagnosis, respectively. SpWB was found to be associated with QoL more strongly than physical and emotional well-being. Peace and Meaning each contributed unique variance to QoL, and their relative importance shifted over time. Faith was positively related to QoL initially. This association became insignificant at three months post-baseline.Significance of results:This study underscores the significance of SpWB for people newly diagnosed with advanced cancer, and it highlights the dynamic pattern of Peace, Meaning, and Faith in association with QoL. Our results confirm that patients newly diagnosed with advanced cancer experience an existential crisis, improve and stabilize over time. Future studies with larger samples over a longer period of time are needed to verify these results.
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FISHCHUK, Natalia. "THE NECESSITY FOR DIAGNOSTICS USING IN THE SYSTEM OF ANTICRISIS MANAGEMENT OF AGRICULTURAL INDUSTRY ENTERPRISES." "EСONOMY. FINANСES. MANAGEMENT: Topical issues of science and practical activity", no. 1 (41) (January 2019): 7–22. http://dx.doi.org/10.37128/2411-4413-2019-1-1.
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The global financial and economic crisis, which began in 2007, is difficult to overcome as it has numerous negative consequences. Ukraine, like the entire post-Soviet space, is burdened with problems of the transformation period, is experiencing difficult times. In recent years, the economic system in the country didn’t get signs of stable development. The crisis, as it is known, is able to break the balance in any sector of the country's economy and in a separate enterprise. The global financial and economic crisis, political instability, imperfection of legislation and insufficient level of state regulatory policy make a significant impact on the activity of domestic enterprises. In order to prevent the negative impact of risk factors on both the external and internal environment, it is necessary to review and improve special tools and approaches of crisis management that are used in the practice of economic activity. Taking into account these and other factors, the article considers the question of the essence and the objective necessity of using of crisis management approaches in the current conditions of agrarian sector enterprises activity. The necessity of forming of crisis management system, conducting of anti-crisis monitoring of the state of enterprises and diagnostics, as its specific function, determining of acceptability of various diagnostic models, need in developing of anti-crisis approaches and strategies for the development of agricultural enterprises have led to the relevance of the chosen topic. Despite the fact that a huge amount of theoretical and applied material has been developed in the world, the theme of crises, crisis management and diagnostics, as its providing component, remains in the sight of foreign and domestic scientists. This problem was particularly acute in agrarian enterprises of Ukraine, due to certain objective reasons. First of all, this is due to the lack of generalized methodological approaches, recommendations and criteria sufficiently adapted to the specific conditions of the domestic agrarian economy and good accounting and reporting system. The purpose of the article is to substantiate the necessity of carrying out diagnostics as the basic function of crisis management; approbation of the use of the most common foreign and domestic methods of diagnosing the crisis, assessing the possibility of their use in the conditions of agricultural enterprises. Ukraine has a strong agro-industrial potential and significant prospects for its future development. This is an essential component of the financial and food safety of the country, which guarantees the further economic development of the country as a whole. The results of agricultural enterprises activity do not correspond with the resource potential and opportunities of the industry. The current crisis, remaining difficult and tense, is a reflection of the accumulated internal economic and political problems reinforced by the effects of the global financial crisis. Opposition to crisis phenomenons and the revival of the normal course of business activity of entrepreneurs need to improve the practice of crisis management of enterprises, increased attention to issues of diagnosis of the level and causes of the crisis, the development of sufficiently adapted methods for its implementation. Diagnostics, being the category of crisis management, aims in-time recognition of the signs and nature of the crisis, the localization of its undesirable effects, is a meaning of obtaining reliable, high-quality information about the actual state and capabilities of the enterprise in the initial stage of the crisis, the basis for the introduction of special methods and mechanisms of crisis management. Bankruptcy diagnostics is a system of targeted financial analysis in order to find and identify the parameters of crisis development that can disbalance the system, reduce its risk-taking and pose a threat of the bankruptcy in the future. Individual features of agricultural enterprises, their condition, reasons and depth of crisis signs require different methods of getting out of a crisis state. There are no universal methods for dealing with the crisis. Therefore, each enterprise must independently develop its plan of anti-crisis actions that will ensure its survival. World experience and practice of crisis management at the enterprise level today offer a number of techniques for conducting bankruptcy diagnostics, both quantitative and qualitative; express and deep analysis of crisis signs. The most well-known and used multifactorial models for the diagnosis of the crisis situation and the prediction of bankruptcy, developed by foreign authors are: the models based on the Z-coefficients of Altman, Springate, Biver, Liss, the predicted models of Taffler and Tisshaw, the Fulmer model, Beerman model, the model of rating numbers of Sayfulin and Kadykov, the score method of Argenti and others. Despite the fact that these models are quite actively used in Ukraine, it is obvious that they are weak in their adaptation to national realities, peculiarities of management, the specifics of domestic practice, and sectoral operating conditions. This explains the possibility of obtaining wrong, biased conclusions, significant errors in evaluating and forecasts. Native theory and practice of crisis management also offer a number of methods for assessing the probability of bankruptcy. Among the most well-known are methods of Yershova N., Matviychuk A., Tereshchenko O., methodology for solvency assessment of Ligonenko L. and Kovalchuk G., Hayvoronskaya Y., and others. They are more adapted to domestic realities and reduce imperfections of foreign models. At the same time, due to individual characteristics and factors of each enterprise, there is no universal model of bankruptcy forecasting. The publication deals with the most common models for predicting of the crisis situation of enterprises, their special features of using and disadvantages. The possibility of using of some foreign and domestic models in the diagnosis of the crisis state of enterprises in order to prevent bankruptcy is explored. Checking of the possibility of using of different models and the objectivity of the obtained results is made on the basis of analytical data of one of the structural subdivisions of the Ukrainian Scientific and Educational Consortsium, the State Enterprise "Experimental Farm "Salyvonkivske" of the Institute of Bioenergetic Cultures and Sugar Beet of the National Academy of Agrarian Sciences of Ukraine. Calculations were carried out according to the models of Altman, Springate, Liss, Biver, which basically operate on indicators of operational, investment and financial activity of the enterprise, and considered with their different level of relaions and mutual influence. Among the national models the methodology of O.Tereschenko and the six-factor model approved by the Ministry of Economy of Ukraine have been used. The obtained results of calculations and their comparison with the limit values demostrate full capacity of the state enterprise "DG" Salyvonkivske" to continue its activity, show condition of financial well-being and the absence of bankruptcy risks. There were no discrepancies in the obtained results. Foreign models are suitable for using in Ukrainian conditions with certain conditions, as evidenced by numerous publications. All of them have their advantages and disadvantages, which are manifested in varying degrees, depending on the features and specifics of the object of analysis, its financial and economic state. It is recommended when using foreign models of diagnostics, to choose such approaches that would enable to obtain a more reliable and accurate assessment of the financial and economic condition, relying on the results of one model analysis is not worthwhile. Careful selection and integrated using of several models at the same time, including specially designed and recommended for domestic enterprises, will significantly increase the reliability and ensure maximum accuracy of forecasts. Conducting of anti-crisis monitoring will enable to detect unwanted deviations in a timely manner and prevent problems, ensuring a stable financial position, which is the main objective of crisis management.
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Milyaeva, L. G. "COMPREHENSIVE DIAGNOSIS OF THE EMPLOYMENT SITUATION IN THE CONTEXT OF HUMAN RESOURCES SECURITY OF THE ENTERPRISE." Economics Profession Business, no. 4 (December 10, 2021): 52–58. http://dx.doi.org/10.14258/epb202155.
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In the context of a crisis economy, the need for an analysis of the employment of enterprise personnel is significantly updated — the most important socio-economic category, which largely determines the level of competitiveness and personnel safety of the economic entity. The theoretical component of the work is devoted to substantiating the essence of the definition of «employment of enterprise personnel», positioned as a system of social and labor relations within the framework of a specific labor cooperation; accordingly, the methodological component of the work is argumentation, description and illustration on conditional examples of seven key points that form the concept of the study of personnel employment at the current research stage. The central place in the article is given to the presentation of the original author’s methodology for a comprehensive (satisfied-structural) assessment of the situation in the field of employment of enterprise personnel, based on the allocation of complex types of employment and the development of the Employment Matrix, which allows you to diagnose the achieved level of personnel security, identify problematic issues and justify targeted management decisions aimed at their normalization. In conclusion, the distinctive features of the methodology are emphasized (simplicity, visibility of the presentation of results, diversification of use, universal nature), and the legality of its replication in specialized publications is justified.
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Sia, Charmaine Si Min, Samantha Hui Ling Cheong, Clara Lee Ying Ngoh, Yi Hern Tan, and Weng Kin Wong. "Critical Coronavirus Disease 2019 in a Hemodialysis Patient: A Proposed Clinical Management Strategy." Case Reports in Nephrology and Dialysis 10, no. 2 (July 30, 2020): 86–94. http://dx.doi.org/10.1159/000509792.
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The coronavirus disease 2019 (COVID-19) pandemic has caused a catastrophic global health crisis. There is a lack of mitigation and clinical management strategies for COVID-19 in specific patient cohorts such as hemodialysis (HD) patients. We report our experience in treating the first case of COVID-19 in a HD patient in Singapore who had a severe clinical course including acute respiratory distress syndrome and propose a clinical management strategy. We propose a clinical workflow in managing such patients based on available evidence from literature review. We also highlight the importance of early recognition and intervention for disease control, dialysis support in an acute hospital isolation facility, deisolation protocol, and discharge planning due to prolonged viral shedding. The case highlights important points specific to a HD patient with a COVID-19 diagnosis, tailored interventions for each stage of the disease, and deisolation considerations in the recovery phase.
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Mirzayeva, Gulgun. "Etymology and diagnosis of family crises." Scientific Bulletin 4 (2019): 66–73. http://dx.doi.org/10.54414/ugdx5438.
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This article reflects on approaches in the modern scientific literature about family crisis issues. The main focus is on the classification and the diagnosis of crises. The development stages of the family as a social system is analyzed and the issues that may cause family crisis risk are mentioned.
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Mizumaki, Hiroki, Shinsuke Takagi, Naoyuki Uchida, Sachie Wada, Kosei Kageyama, Daisuke Kaji, Aya Nishida, et al. "Allogeneic Hematopoietic Cell Transplantation Is a Curative Treatment Option for Advanced-Stage Chronic Myeloid Leukemia in the TKI Era, a Single Institution Retrospective Study of 29 Post AP/BC Cases." Blood 124, no. 21 (December 6, 2014): 5931. http://dx.doi.org/10.1182/blood.v124.21.5931.5931.
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Abstract BACKGROUND: The prognosis of chronic myeloid leukemia (CML) in advanced stages (accelerated phase, AP or blast crisis, BC) is still extremely poor even with tyrosine kinase inhibitors (TKIs) and allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for them. METHOD: Using our database, we retrospectively collected CML patients transplanted at Toranomon Hospital between June 2004 and March 2014, after the introduction of TKIs in Japan. RESULT: Twenty-nine consecutive patients were extracted. The median age was 52 years (range; 16-70). The disease status at diagnosis was chronic phase (CP, n=11), accelerated phase (AP, n=5) and blast crisis (BC, n=13). All the patients were treated with TKIs before transplantation, including imatinib (n=15), nilotinib (n=1), dasatinib (n=6), imatinib/dasatinib (n=4), nilotinib/dasatinib (n=1) and imatinib/nilotinib/dasatinib (n=2). All the 11 patients in CP at diagnosis progressed into AP/BC in their course and only 3 patients achieved second CP (MinorCyR, n=1; PCyR, n=1; MMR, n=1) at transplantation. On the other hand, 11 of 18 patients in AP/BC at diagnosis achieved CP (MinorCyR, n=1; PCyR, n=4; CCyR, n=3; MMR, n=3) at transplantation and the remaining 7 patients did not achieve CHR (Fig. 1). The median HCT-CI and EBMT score at transplantation was 2 (range, 0-5) and 5 (range, 0-7), respectively. Additional cytogenetic abnormalities developed until transplantation in 8 of 11 patients (73%) in CP at diagnosis and in 11 of 18 (61%) in AP/BC at diagnosis. Point mutations in ABL gene were detected in 9 of 20 patients (45%) in their course. Four of 7 patients (57%) in CP at diagnosis had ABL mutations, including T315I (n=1), E255K (n=2) and L359C (n=1). Five of 13 (38%) in AP/BC at diagnosis had ABL mutations, including T315I (n=4) and V299L (n=1). Overall, 14 of 29 (48%) patients underwent transplantation in CP stage (MinorCyR, n=2; PCyR, n=5; CCyR, n=3; MMR, n=4). The donors were related PBSC (n=6), unrelated BM (n=4) or unrelated CB (n=19). The conditioning regimens were myeloablative in 20 patients and reduced-intensity in 9. Twenty-seven patients achieved neutrophil engraftment at a median day of 19 (range, 10-34). The cumulative incidence of neutrophil engraftment was 93.1% at day 42 (patients engrafted, n=27; dead before day 19, n=2). At 3 years, the cumulative incidence of relapse and non-relapse mortality was 32.3% and 14.0%, respectively. In 15 patients who did not achieve CP before transplantation, 11 patients (73.3%) achieved CR after transplantation. With a median follow-up of survivors of 1144 days (range, 127-3705), overall survival (OS) and event free survival (EFS) at 3 years was 63.2% and 56.3%, respectively. In univariate analysis, age (<53 vs. ≥53, p=0.19), EBMT score (<5 vs. ≥5, p=0.32) and donor selection (rPB/uBM vs. uCB, p=0.17) had no impact on OS at 3 years. The variables that influenced on OS were disease status at transplantation (CP vs. AP/BC, 85% vs. 42%, p=0.012), karyotype (sole Ph-chromosome vs. additional cytogenetic abnormalities, 90% vs. 47.5%, p=0.042) and conditioning regimen (MAC vs. RIC, 72.7% vs 41.7%, p=0.039). In multivariate analysis, the only variable that influenced on OS was disease status at transplantation (HR=0.16, 95% CI 0.04-0.70, p=0.015). No patients received maintenance therapy with TKIs. All 9 patients who relapsed after transplantation were re-treated with TKIs. Three patients achieved MMR and the remaining 6 patients who failed received 2nd transplantation. CONCLUSION: We concluded that allo-HCT from any cell sources is a curative treatment option even for the CML patients who had AP/BC stage during their course of the disease. Remarkably good OS can be expected for those who achieved CP status before transplantation, suggesting better disease control before allo-HCT could be one of the critical factors to improve the final outcome. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
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Cheke, Rameshwar S., Sachin Shinde, Jaya Ambhore, Vaibhav Adhao, and Dnyaneshwar Cheke. "Coronavirus: Hotspot on coronavirus disease 2019 in India." Indian Journal of Medical Sciences 72 (April 30, 2020): 29–34. http://dx.doi.org/10.25259/ijms_33_2020.
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The novel coronavirus disease (COVID-19) or also known as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recognized as the cause of respiratory infection in Wuhan, Hubei Province, China, in late December 2019. As of April 5, 2020, this epidemic had spread to worldwide with 12,03,485 confirmed cases, including 62,000 deaths. The World Health Organization has declared it a Global Public Health Crisis. Coronavirus causes respiratory illness coughing, sneezing, breathlessness, and fever including pneumonia. The disease is transmitted person to person through infected droplets. At present, the research on novel coronavirus is still in the primary stage. Based on the published study, we thoroughly summarize the history and origin, microbiology and taxonomy, mode of transmissions, target receptor, clinical features, diagnosis, prevention, and treatment about COVID-19. This short report writes in hope for providing platform to community and researcher dealings against with the novel coronavirus and providing a reference for further studies.
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Grossmann, Vera, Melanie Zenger, Alexander Kohlmann, Susanne Schnittger, Wolfgang Kern, Martin C. Mueller, Andreas Hochhaus, Torsten Haferlach, and Claudia Haferlach. "Complete or Partial Deletions of IKZF1 Occur In 28% of Blast Crisis CML and Are the Only Recurrent Submicroscopic Alteration Associated with Disease Progression: An Analysis of 43 Cases Using High-Resolution Genome-Wide Copy Number DNA Arrays and Molecular Assays." Blood 116, no. 21 (November 19, 2010): 4172. http://dx.doi.org/10.1182/blood.v116.21.4172.4172.
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Abstract Abstract 4172 In advanced CML, approximately 80% of patients develop additional non-random cytogenetic abnormalities in Ph+ cells. However, little is known about molecular mutations leading to disease progression. Only limited changes that occur in the clonal evolution of the chronic phase to blast crisis, both in gene expression patterns and DNA copy number alterations, have been described. Novel technologies allow comprehensive detection of additional molecular genomic aberrations. To identify recurrent submicroscopic gains and losses, as well as copy neutral loss of heterozygocity (CN-LOH), we employed whole-genome 2.7M arrays (Affymetrix, Santa Clara, CA) to study 22 cases with blast crisis CML (n=14 myeloid; n=6 lymphoblastic; n=2 not specified) and 18 cases of untreated patients in chronic phase, matched for age and gender. In four cases, the analyses were performed on paired samples. We first investigated the occurrence of CN-LOH and observed in two patients with blast crisis a recurrent CN-LOH for 1p (both ranging to the telomere as being typical for acquired CN-LOH). Secondly, all aberrations identified by chromosome banding analysis were also detected by microarray analysis. The microarray used provided copy number estimates for 2.7 million markers, thus, even very small gains and losses were identified. As such, 39 submicroscopic variations were found, which were not detectable by chromosome banding analysis. Aberrations occurred predominantly in blast crisis CML: number of alterations in chronic phase vs. blast crisis, n=4 vs. n=9 gains, n=7 vs. n=16 losses, and n=0 vs. n=3 CN-LOHs; e.g. gains for AKT2, MLLT4, ELN, and losses of CBFB, MLLT10 or MYC, respectively. Besides microdeletions in the breakpoint region of BCR (n=5) and ABL1 (n=5), the only recurrent submicroscopic alteration was a deletion confined to a subset of exons from the IKZF1 gene, located on the short arm of chromosome 7 (7p12.2), and was observed in three patients in the cohort of blast crisis. In addition, in three patients of blast crisis cohort a complete or partial monosomy 7p had been identified. IKZF1 encodes for a transcription factor which is an important regulator of lymphoid cell differentiation. To further investigate the role of IKZF1 deletions, additional 21 patients with blast crisis CML (n=14 myeloid; n=4 lymphoblastic; n=3 not specified) were screened. In this independent cohort, two patients showed monosomy 7 in chromosome banding analyses and in four patients deletions of internal IKZF1 exons were identified by PCR using specific primer pairs for the common deletions in the IKZF1 gene as described by Iacobucci et al. (Blood, 114:2159-67, 2009). In total, for both cohorts of blast crisis CML, in 28% (12/43) of cases either complete loss of IKZF1 due to cytogenetic aberrations leading to loss of 7p or intragenic IKZF1 deletions were observed. Of note, these aberrations never occurred concomitantly. In detail, a complete deletion of IKZF1 was detected in 5 patients due to a derivative chromosome 7 or a monosomy 7: 2/5 cases with lymphoblastic blast crisis and 2/5 cases with myeloid blast crisis (1/5 case not specified). A partial deletion of IKZF1 was found in 7 cases: 5/7 cases with partial IKZF1 deletions presented with lymphoblastic blast crisis and 1/7 case with myeloid blast crisis (1/7 case data not specified). In detail, in five cases the common partial deletion of exons 4–7 was detected, resulting in a dominant negative isoform, one case was harboring the exons 2–7 deletion, and another case was carrying both of the two mutations. In three of the seven cases with an intragenic IKZF1 deletion, matched DNA from the first diagnosis and chronic state was available. The respective IKZF1 deletions were not detectable in these specimens indicating that IKZF1 deletions developed during disease progression. Moreover, in one patient we performed a serial analysis of 8 time points across different disease states (interval from diagnosis to most recent investigation: 2.2 years). Here, exons 2–7 deletion was only detected at the stage of blast crisis. In addition, in 4 of 7 cases with a partial deletion of IKZF1 a point mutation in BCR-ABL1 (E279K, T315I, F317L, Q252H) was detected. In conclusion, these results underline a pathogenetic contribution of IKZF1 deletions to disease progression in CML and therefore constitute an important progression marker to blast crisis. Disclosures: Grossmann: MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership, Research Funding.
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Abdel-Razeq, Hikmat, Faris Tamimi, Nayef Abdel-Razeq, Maryam El-Atrash, Baha’ Sharaf, Rawan Mustafa, Razan Mansour, and Rayan Bater. "Late presentation and suboptimal treatment of breast cancer among Syrian refugees: a retrospective study." Journal of International Medical Research 49, no. 5 (May 2021): 030006052110184. http://dx.doi.org/10.1177/03000605211018448.
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Objectives The crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management of Syrian patients with breast cancer treated at our institution. Methods We retrospectively collected data on Syrian refugees treated for breast cancer over the past 10 years at our center. Management was compared against our approved clinical practice guidelines. Results A total of 113 patients were eligible and included. The median age (range) at diagnosis was 47 (21–84) years and most women presented with locally advanced or metastatic disease (n = 74, 65.5%). Breast-conserving surgery and breast reconstruction were performed in 27 (33.8%) and 11 (35.4%) patients, respectively. Only a few patients received targeted (35.5%) or advanced endocrine therapy (30.0%). In total, 37 (32.7%) patients had considerable deviations from our institutional treatment guidelines and had worse outcomes. Conclusions Syrian refugees with breast cancer present late, have more advanced-stage disease, and are more likely to receive delayed and suboptimal therapy. An international systematic approach for cancer care among such vulnerable populations is urgently needed.
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Hassanzadeh, Shakiba, Arjang Djamali, Leila Mostafavi, and Aiyoub Pezeshgi. "Kidney complications following COVID-19 vaccination; a review of the literature." Journal of Nephropharmacology 11, no. 1 (August 30, 2021): e1-e1. http://dx.doi.org/10.34172/npj.2022.01.
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Objective: To review the reported cases of kidney injury following vaccination for coronavirus disease 2019 (COVID-19) with a focus on renal pathology. Methods: We searched for case reports of kidney complications after COVID-19 vaccine in PubMed. Results: A total of 36 articles including 49 case reports were reported. These included minimal change disease (n=17), IgA nephropathy (IgAN) (n=15), IgA nephritis/vasculitis (n=5), ANCA glomerulonephritis/vasculitis (n=5), anti-glomerular basement membrane (GBM) nephritis (n=2), and 1 case of each granulomatous vasculitis, acute tubulointerstitial nephritis, scleroderma renal crisis, IgG4-related disease nephritis, and primary membranous nephropathy (MN). Conclusion: We give an overview of the reported cases of post-COVID-19 renal complications. Further investigations of the underlying pathogenesis of post-COVID-19 vaccination renal adverse events are required, as prompt workup, diagnosis, and treatment of patients with renal complications may lead to complete remission, prevent kidney failure, and long-term complications such as end-stage renal disease (ESRD). However, these complications are overall extremely rare and the benefit of vaccination outweighs the potential risks.
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Harris, James B., Bhuvana Sunil, Michael K. Ryan, and Giovanna Beauchamp. "Association of Slipped Capital Femoral Epiphysis With Panhypopituitarism Due to Pituitary Macroadenoma: A Case Report." Journal of Investigative Medicine High Impact Case Reports 9 (January 2021): 232470962199995. http://dx.doi.org/10.1177/2324709621999956.
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Slipped capital femoral epiphysis (SCFE) commonly occurs in overweight or obese adolescents, but can also be associated with endocrine disorders including hypothyroidism, pituitary tumors, and growth hormone deficiency. In this article, we present a case of panhypopituitarism that initially presented with SCFE. A 16-year-old male presented with right SCFE. After a right hip open reduction and percutaneous pinning procedure, findings of skeletal maturity that lagged behind his chronologic age and a delayed Tanner stage resulted in a referral to an endocrine specialist. Endocrine laboratory evaluation identified elevated prolactin levels (1493 ng/mL), hypogonadotropic hypogonadism, and central adrenal insufficiency as evidenced by low morning cortisol level of 1.0 µg/dL. Magnetic resonance imaging revealed a large pituitary T2 isointense mass measuring 1.8 × 2.7 × 2.3 cm. The patient was diagnosed with panhypopituitarism due to a pituitary macroadenoma. Multidisciplinary collaboration for treatment of this patient consisted of oral cabergoline, oral levothyroxine, oral hydrocortisone therapy, intramuscular testosterone therapy, and a prophylactic closed reduction percutaneous pinning of the left hip due to high risk of also developing SCFE of the left hip. Panhypopituitarism should be considered as a diagnosis after atypical presentations of SCFE. In our case, an astute clinical assessment resulted in prompt endocrine referral and management of panhypopituitarism. Our report highlights the importance of multidisciplinary collaborations to guarantee early detection of endocrinopathies in patients with SCFE undergoing surgical interventions in order to avoid potential complications, such as adrenal crisis during surgery.
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Danyk, Yu, O. Zborovska, and N. Rodina. "Models and mechanisms of formation of posttraumatic stress disorders in hybrid war (conflicts) and their features." Fundamental and applied researches in practice of leading scientific schools 31, no. 1 (February 28, 2019): 44–53. http://dx.doi.org/10.33531/farplss.2019.1.09.
Full textAbstract:
In study was conducted analysis and systematic studies of war syndromes, the end of the 20th and early 21st centuries ("Vietnamese syndrome", "Persian Gulf syndrome", "Afghan syndrome," etc.). For the first time are presented the systemic symptoms of the hybrid war syndrome (hybrid conflict) on the basis of the analysis, the application of the method of historical analogies, comparison, systematization and interpretation of facts, abstraction and concretization.
For the first time, the presence of the following stages of its development in the process of formation of PTSD has been proven: the "pre-PTSD", the latent phase "soft PTSD" (which already takes place, but obviously does not manifest itself and can be detected only by instrumental (hardware) methods) and "formed PTSD" (as a rule, one that is completely formed, clearly manifested, stable, multisymptomatic, and deployed, which, in the absence of its timely detection and treatment, is more likely to be transformed into a post-traumatic personality disorder).
The issues of informational and cognitive trauma of personnel and population were considered on the basis of the analysis of the striking factors of information and cognitive weapons and the peculiarities of their salvage in the Hybrid War.
We identified and described in our model of formation of PTSD in the context of the hybrid war "zero" - "entry into military service" stage and the three main stages of the emergence and formation of the PTSD.
The first stage is "preparatory": Phases: 1) General training; 2) training in the units in the conditions most close to combat (primary "Vaccinations" from PTSD); 3) Combat coordination of units (secondary "Vaccinations" from PTSD). The second stage of "stay in the crisis zone": 1) phase - sending to the area of military action; 2) participation in military action; 3) retirement. The third stage "Return from the combat zone". Particular emphasis should be put on other models of PTSD formation in specialists who do not take direct participation in battles, but are in a state of high nervous-psychological stress.
Stress is due the influence of responsibility for the effectiveness of use in the area of military action or in the enemy territory of high-cost, high-tech means on which the effectiveness of action depends in general, and the lives of combatants (for example, LAC crews and, in particular, UAV operators (2nd model) and military pilots flying aircraft (airplanes / helicopters) (3rd moth model). The first and second stages of the formation of PTSD in them are similar to the above-mentioned one model of the formation of PTSD. Differences with the 1st model and between the second and third models develop in the third stage.
It has also been established that PTSD may occur immediately after a traumatic event, or can lead to a negative long-term symptom and show symptoms that are sufficient for the diagnosis of PTSD (or the conditions / illness associated with it), even over the years.
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Zhu, Kangying, Zhigang Sun, Fenghua Zhao, Ting Yang, Zhenrong Tian, Jianbin Lai, Wanxue Zhu, and Buju Long. "Relating Hyperspectral Vegetation Indices with Soil Salinity at Different Depths for the Diagnosis of Winter Wheat Salt Stress." Remote Sensing 13, no. 2 (January 13, 2021): 250. http://dx.doi.org/10.3390/rs13020250.
Full textAbstract:
Abundant shallow underground brackish water resources could help in alleviating the shortage of fresh water resources and the crisis concerning agricultural water resources in the North China Plain. Improper brackish water irrigation will increase soil salinity and decrease the final yield due to salt stress affecting the crops. Therefore, it is urgent to develop a practical and low-cost method to monitor the soil salinity of brackish irrigation systems. Remotely sensed spectral vegetation indices (SVIs) of crops are promising proxies for indicating the salinity of the surface soil layer. However, there is still a challenge concerning quantitatively correlating SVIs with the salinity of deeper soil layers, in which crop roots are mainly distributed. In this study, a field experiment was conducted to investigate the relationship between SVIs and salinity measurements at four soil depths within six winter wheat plots irrigated using three salinity levels at the Yucheng Comprehensive Experimental Station of the Chinese Academy of Sciences during 2017–2019. The hyperspectral reflectance was measured during the grain-filling stage of winter wheat, since it is more sensitive to soil salinity during this period. The SVIs derived from the observed hyperspectral data of winter wheat were compared with the salinity at four soil depths. The results showed that the optimized SVIs, involving soil salt-sensitive blue, red-edge, and near-infrared wavebands, performed better when retrieving the soil salinity (R2 ≥ 0.58, root mean square error (RMSE) ≤ 0.62 g/L), especially at the 30-cm depth (R2 = 0.81, RMSE = 0.36 g/L). For practical applications, linear or quadratic models based on the screened SVIs in the form of normalized differential vegetation indices (NDVIs) could be used to retrieve soil salinity (R2 ≥ 0.63, RMSE ≤ 0.62 g/L) at all soil depths and then diagnose salt stress in winter wheat. This could provide a practical technique for evaluating regional brackish water irrigation systems.
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Sudarsan, P. K. "UNDERSTANDING FINANCIAL CRISIS: A THEORETICAL ANALYSIS." Ushus - Journal of Business Management 2, no. 1 (January 1, 2003): 1–10. http://dx.doi.org/10.12725/ujbm.2.1.
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Financial crises and their sub set banking crises have become worldwide phenomena in recent years. Understanding of financial crises assumes importance because the success of policy prescriptions to cure these crises depends to a large extent on the proper diagnosis of these crises. The objective of this paper is to provide a theoretical analysis to understand the financial crisis in a better way. The poper conjectures three stages in the financial crisis: confidence crisis, currency crisis and financial crisis. Paper shows that confidence crisis leads to the currency crisis and currency crisis in turn advances into the financial crisis. The paper also highlights the two-way linkage between currency crisis and financial crisis and its implications on policy suggestions. The two-way linkage between the currency crisis and financial crisis makes the policy prescriptions difficult. IMF policy to cure the East Asian crisis failed initially mainly because of this reason. The theoretical analysis reveals that a judicious mix of different policies would be the best remedy for the financial crisis of the type occurred in East Asia, though this would take some time to show positive results.
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Wicke, Daniel C., Johann Meyer, Guntram Büsche, Hans Kreipe, Zhixiong Li, Karl Welte, Matthias Ballmaier, Christopher Baum, and Ute Modlich. "Ectopic Expression of the Extracellular Domain of Mpl Is Sufficient to Induce a Hematopoietic Population Crisis." Blood 112, no. 11 (November 16, 2008): 2886. http://dx.doi.org/10.1182/blood.v112.11.2886.2886.
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Abstract The thrombopoietin receptor Mpl is required for regeneration of hematopoietic stem cells and governs megakaryocytic differentiation. Patients with inherited MPL deficiency suffer from severe thrombocytopenia which progresses to aplastic anemia, a disorder called congenital amegakaryocytic thrombocytopenia (CAMT). As a first step towards a potential gene therapy for MPL deficiency, we retrovirally expressed the receptor in a murine bone marrow transplantation model. An initial series of vectors used a strong enhancer-promoter derived from the spleen-focus forming virus (SFFV). Mice transplanted with hematopoietic cells modified by these constructs developed a profound yet transient elevation of multi-lineage hematopoiesis due to increased signaling of the Thpo receptor on target and non-target cells. Mice developed increased leukocyte, erythrocyte and platelet counts (2–3 times elevated) compared to GFP control animals. Histopathology revealed an elevated number of mature megakaryocytes with atypical features like numerous giant forms in the bone marrow and the spleen and atypical neoformation of bone in the spleen leading to the diagnosis of chronic myeloproliferative disorder (CMPD). A minority of mice (3/27) developed erythroleukemia with almost 100% CD71 and TER119 double positive cells as detected by flow cytometry. Histopathology presented infiltration of erythroblasts in all hematopoietic tissues like the BM, spleen and liver. Molecular analysis revealed retroviral vector insertions in sfpi1, fli1 and klf3 that seem to be the major driving force for the development of leukemia in these animals. Somewhat unexpectedly, in the majority of mice the CMPD converted into a progressive, potentially lethal pancytopenia. Animals had severely reduced blood cell counts with only 50% of leukocyte, 20% of erythrocyte and 10% of platelet counts compared to GFP control animals. This population crisis affected all major blood lineages and also involved co-existing unmodified hematopoiesis. Histopathology presented a dysmegakaryopoiesis with an increased number of atypical micro-megakaryocytes, histiocytes with erythrocytophagocytosis and atypical mast cell proliferation diagnosed as a myelodysplastic syndrome (MDS)-like disorder. In the bone marrow, pancytopenic mice had reduced cell numbers of the primitive cell fraction (LSK cells). To address the mechanism of pancytopenia, we expressed a dominant negative form of Mpl (dnMpl) consisting of the extracellular and transmembrane domain and lacking the intracellular signal transduction domain. Animals transplanted with dnMpl-modified cells failed to show the initial CMPD but developed the same pancytopenic, MDS-like end stage. A vector expressing Mpl under control of the PGK promoter or a fragment of the Mpl-promoter reduced or completely avoided the side effects (CMPD, MDS-like disorder) observed with vectors using stronger promoters. The induction of a hematopoietic population homeostasis thus depends upon Mpl expression levels, indicating the need for strictly regulated transgene expression in gene therapy for MPL deficiency. As ectopic expression of the extracellular domain is sufficient to cause MDS, sequestration of crucial niche factors like Thpo may contribute to the pathogenesis of this disorder. This study demonstrates that ectopic expression of a hematopoietic growth factor receptor may disturb organ homeostasis through interference with intra- and extracellular mechanisms of cell communication.
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Mursalim, Muhammad Khaerul Naim, and Ade Kurniawan. "Multi-kernel CNN block-based detection for COVID-19 with imbalance dataset." International Journal of Electrical and Computer Engineering (IJECE) 11, no. 3 (June 1, 2021): 2467. http://dx.doi.org/10.11591/ijece.v11i3.pp2467-2476.
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COVID-19, which originated from Wuhan, rapidly spread throughout the world and became a public health crisis. Recognizing the positive cases at the earliest stage was crucial in order to restrain the spread of this virus and to perform medical treatment quickly for patients affected. However, the limited supply of RT-PCR as a diagnosis tool caused greatly delay in obtaining examination results of the suspected patients. Previous research stated that using radiologic images could be utilized to detect COVID-19 before the symptoms appeared. With the rapid development of Artificial intelligence in medical imaging in recent years, deep learning as the core of this technology could achieve human-level-performance in diagnostic accuracy. In this paper, deep learning was implemented to detect COVID-19 using a chest X-ray dataset. The proposed model employed a multi-kernel convolution neural network (CNN) block combined with pre-trained ResNet-34 to overcome an imbalanced dataset. The model block adopted different kernel sizes as follows 1x1, 3x3, 5x5, and 7x7. The findings show that the proposed model is capable of performing binary and three class classification tasks with an accuracy of 100% and 93.51% in the validation phase and 95% and 83% in the test phase, respectively.
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Xue, Mengxing, Zhao Zeng, Qinrong Wang, Lijun Wen, Yi Xu, Jundan Xie, Qian Wang, Changgeng Ruan, Depei Wu, and Suning Chen. "Mutational Profiles during the Progression of Chronic Myeloid Leukemia." Blood 138, Supplement 1 (November 5, 2021): 3596. http://dx.doi.org/10.1182/blood-2021-154273.
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Abstract Background: Despite significant improvements in the prognosis of chronic myeloid leukemia (CML) achieved by targeted therapy with tyrosine kinase inhibitors (TKIs), a small proportion of cases may not respond to TKIs or may relapse after an initial response, and then progress from chronic phase (CP) to blastic crisis (BC), characterized by a dismal prognosis. It remained uncertain whether the genetic lesions in addition to the BCR-ABL1 fusion could predict clinical outcomes of CML in the TKI era. Aim: To study the mutational profiles at each stage of CML and the prognostic significance of somatic mutations in addition to the BCR-ABL1 fusion in the TKI era. Patients and Methods: We performed targeted sequencing in 81 CML patients chosen retrospectively. 10 patients had optimal response to TKIs by European LeukemiaNet criteria and maintained durable major molecular response more than 5 years. 71 patients had progressed to accelerated phase (AP) or BC, of whom 43 had sequencing performed at paired CP and AP/BC samples, 28 at AP or BC samples. Totally, we analyzed 53 CP, 20 AP, and 61 BC samples. The targeted resequencing gene panel, covering 386 genes which were recurrently mutated in hematologic malignancies, were performed on a HiSeq 4000 NGS platform (Illumina). Results: Among the 53 CP samples, 20 (37.7%) had mutations involving 14 genes, and the number of mutated genes in each patient was 0-3 (median 0). ASXL1 was the most commonly mutated gene, 10/53 (18.9%) patients had this mutation, followed by KMT2D (4/53, 7.5%), PC (2/53, 3.8%), ERBB4 (2/53, 3.8%). ASXL1 mutation mainly existed in 43 patients with progressed disease , while only one case carried this mutation in 10 patients responsive to TKIs (20.9% vs 10%). 17/20 (85%) AP samples (including 10 patients progressed to AP and the other 10 patients who eventually progressed to BC from AP ) carried mutations involving 18 genes, the number of mutated genes in each patient was 0-6 (median 1.5). ABL1 was the most commonly mutated gene, and 8/20 (40%) patients had this mutation. The second was the ASXL1 mutation, 7 (7/20, 35%) patients carried this mutation. The other genes mutated in more than 2 patients included BCORL1 (3/20, 15%), RUNX1 (2/20, 10%), PHF6 (2/20, 10%), KMT2D (2/20, 10%), ATM (2/20, 10%). 54/61 (88.5%) BC samples (44 with myeloid crisis, 14 with lymphoid crisis, 3 with mixed phenotypic crisis) carried mutations, involving 41 genes, and the number of mutated genes in each patient was 0-9 (median 2). Similar to the mutation status in AP, the most commonly mutated gene was also ABL1, 24/61 (39.3%) patients carried this gene mutation, followed by ASXL1 mutation (13/61, 21.3%), and the other genes were in order, RUNX1 (11/61, 18.0%), WT1 (8/61, 13.1%), GATA2 (6/61, 9.8%), MED12 (5/61, 8.2%), IDH1 (5/61, 8.2%), TP53 (4/61 , 6.6%), KMT2D (4/61, 6.6%), etc. (Figure 1A) Among all the samples, 34 nonsynonymous variants in the ASXL1 gene were identified in 31 samples of 21 patients ( 3 samples with two variants). All the variants were frameshift and nonsense mutations, localized at the last exon of the ASXL1 gene. 13/21 patients with ASXL1 mutations had multi-stage samples. The median VAF of the ASXL1 mutations in the advanced stage was 31.4% (0-47.0%), which was significantly higher than that in CP at diagnosis (7.0%, 0-27.2%, P=0.033). Most of the ASXL1 mutations detected in CP expanded at the advanced disease, and were accompanied with other additional gene abnormalities, such as ABL1, RUNX1 and WT1 mutations, with the VAF similar to or lower than that of the ASXL1 mutations. In a few cases, the ASXL1 mutant clones in the CP disappeared, suggesting that some ASXL1 mutations may be clonal hematopoiesis unrelated to disease progression.(Figure 1B) In order to evaluate the effects of ASXL1 mutations on sensitivity to TKIs in vitro. We co-expressed P210-BCR-ABL1 fusion and ASXL1 mutation (G646Wfs*12) in Ba/F3 cells. Compared to Ba/F3 cells co-expressing BCR-ABL1 fusion and ASXL1 mutation (Ba/F3-BA/As), Ba/F3-BCR-ABL1 cells without ASXL1 mutation (Ba/F3-BA/Ve) showed higher sensitivity to TKIs, including imatinib, dasatinib and nilotinib.(Figure 1C) Conclusions: These results demonstrated the genetic lesions accumulated during the progression of CML from CP to BC. ASXL1 mutations were the most common genetic lesion in CP at diagnosis and may confer a poor prognosis, as it reduced the sensitivity to TKIs. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.