ObjectivesCold crystalloid cardioplegia for donor heart harvesting and cold ischemic storage conditions during the transportation is the standard of care during heart transplantation procedure. Organ care system (OCS) was introduced for more prolonged and reliable ex vivo organ management. This study evaluated the two different techniques used for myocardial preservation during the procurement and transportation of the heart using the OCS.MethodsWe performed prospective analysis of 43 patients with heart failure undergoing heart transplantation and using the OCS for donor organ transport. Donor hearts were arrested using blood cardioplegia and conditioning (n = 30) or standard Custodiol (SC) solution ( n = 13). Perfusion and cardiac function parameters were continuously monitored while the donor hearts were perfused in the OCS. Impact of preservation techniques on biochemical parameters and clinical outcomes were evaluated.ResultsAll donor hearts had stable perfusion and lactate characteristics in the OCS, with similar measures between the two groups at the beginning of the ex vivo perfusion. Ex vivo heart perfusion mean ending concentration of Interleukin (IL)‐6 and IL‐8 was significantly lower in the blood cardioplegia group compared to the standard care group. Clinical outcomes were comparable between the two groups of patients.ConclusionsThe use of blood cardioplegia and conditioning could be a safe method for myocardial protection in distant procurement and preservation of donor hearts in the OCS.

As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. The drugs exhibiting an RMSD of ≤ 3.0 Å were further analyzed using molecular docking, molecular dynamics (MD) simulation, and post-MD analyses. Using these approaches, we found 12 drugs that showed strong interactions with SARS-CoV-2 helicase amino acids. The analyses were performed using the recently available SARS-CoV-2 helicase structure (PDB ID: 5RL6). Based on the MM-GBSA approach, out of the 12 drugs, two drugs, namely posaconazole and grazoprevir, showed the most favorable binding energy, − 54.8 and − 49.1 kcal/mol, respectively. Furthermore, of the amino acids found conserved among all human coronaviruses, 10/11 and 10/12 were targeted by, respectively, grazoprevir and posaconazole. These residues are part of the crucial DEAD-like helicase C and DEXXQc_Upf1-like/ DEAD-like helicase domains. Strong interactions of posaconazole and grazoprevir with conserved amino acids indicate that the drugs can be potent against SARS-CoV-2. Since the amino acids are conserved among the human coronaviruses, the virus is unlikely to develop resistance mutations against these drugs. Since these drugs are already in use, they may be immediately repurposed for SARS-CoV-2 therapy.

Background: Risk factors for medium to long-term mortality after stroke are well-established but predictors of in-hospital stroke mortality are less clearly characterized. Kazakhstan has the highest age-standardized mortality rate from ischemic stroke in the world.Methods: We performed a retrospective analysis of patients with stroke who were admitted over a 3.5-years period to the neurocritical care unit of a tertiary care hospital in Nur-Sultan, Kazakhstan.Results: In total, 148 critically ill patients were included in the analysis (84 ischemic stroke, 64 hemorrhagic stroke). The mean age was 63 years, 45% were male and the mean Glasgow Coma Score (±SD) at baseline was 10.3 (±3.4). The in-hospital mortality rate was similar in patients with ischemic (36%) and hemorrhagic (39%) stroke (HR 0.88, 95%CI 0.48–1.60). Median survival was 38 days (range: 1–89 days) in patients with ischemic stroke and 39 days (range: 1–63 days) in patients with hemorrhagic stroke. Univariable analysis found that patients who had a lower Glasgow Coma Scale, were in coma and who had cerebral edema were more likely to die in-hospital (P = 0.04, 0.02, <0.01, respectively).Conclusions: Our analysis showed that mortality risk in critically ill patients with hemorrhagic stroke was closer to mortality risk in patients with ischemic stroke than has been reported in other analyses. Hypertension, chronic heart failure, ischemic heart disease and atrial fibrillation were the most frequent comorbidities in patients who developed severe (life-threatening) stroke. Coma and cerebral edema on admission appear to be associated with poor outcome. This is the first publication of in-hospital stroke mortality from a Central Asian population and could form the basis for future research including development of risk scores and identifying modifiable risk factors.

Objectives: The aim of this study was to assist in the development of a health technology assessment (HTA) program for the Ministry of Health (MOH) of the Republic of Kazakhstan.Methods: Mentoring of an initial HTA program in Kazakhstan was provided by the Canadian Society for International Health (CSIH) by means of a partnership with the Kazakhstan MOH. HTA materials, courses, and one-on-one support for the preparation of a series of initial HTA reports by MOH HTA staff were provided by a seven-member CSIH team over a 2.5-year project.Results: Guidance documents on HTA and institutional strengthening were prepared in response to an extensive set of deliverables developed by the MOH and the World Bank. Introductory and train-the-trainer workshops in HTA and economic evaluation were provided for MOH staff members, experts from Kazakhstan research institutes and physicians. Five short HTA reports were successfully developed by staff in the Ministry's HTA Unit with assistance from the CSIH team. Challenges that may be relevant to other emerging HTA programs included lack of familiarity with some essential underlying concepts, organization culture, and limited time for MOH staff to do HTA work.Conclusions: The project helped to define the need for HTA and mentored MOH staff in taking the first steps to establish a program to support health policy decision making in Kazakhstan. This experience offers practical lessons for other emerging HTA programs, although these should be tailored to the specific context. Results: Guidance documents on HTA and institutional strengthening were prepared in response to an extensive set of deliverables developed by the MOH and the World Bank.Introductory and train-the-trainer workshops in HTA and economic evaluation were provided for MOH staff members, experts from Kazakhstan research institutes and physicians. Five short HTA reports were successfully developed by staff in the Ministry's HTA Unit with assistance from the CSIH team. Challenges that may be relevant to other emerging HTA programs included lack of familiarity with some essential underlying concepts, organization culture, and limited time for MOH staff to do HTA work. Conclusions:The project helped to define the need for HTA and mentored MOH staff in taking the first steps to establish a program to support health policy decision making in Kazakhstan. This experience offers practical lessons for other emerging HTA programs, though these should be tailored to the specific context. Keywords: Health technology assessment, Kazakhstan, Mentoring, Global health Acknowledgements:

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups’ stratification along with specific biomarkers’ identification will ensure low recurrence and decrease mortality rates in young women with EC.