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Aim: Electronic prescribing has allowed for the collection of prescription data in real time in Greece for the first time. Hence, the aim of the current study was to present the characteristics of prescriptions for the Greek population during the period from 2015 to 2021. Methods: This retrospective study was based on data extracted from the nationwide Greek electronic prescription database between January 2015 and December 2021. Descriptive statistics methods were used for the needs of the study. As the basic figures examined depend on the size of the population, in order for the results to be comparable, we estimated the corresponding measures per inhabitant, using population data from the Greek Statistical Authority. Appropriate indicators for the comparison of consumption and expenditure over time were estimated. A study of the trend was also carried out using time series and linear regression models. In order to facilitate the design and implementation of specialized policies, it is useful to identify the drug categories with the highest consumption and expenditure, as well as the geographical areas that present similar characteristics. For the first, ABC analysis was used, which helps to identify the most popular categories of drugs, while for the second, cluster analysis was carried out. Agglomerative clustering was used to divide the regions into similar groups. This hierarchical clustering algorithm classifies the population into several clusters, with areas in the same cluster being more similar, and areas in different clusters being dissimilar. The Ward linkage method with Euclidean distance was used. Results: The analysis of prescription drug consumption and expenditure from 2015 to 2021 revealed significant fluctuations and trends across various drug categories, age groups, and geographical areas. Notably, the quantity of prescriptions increased by 20% since 2015, while expenditure surged by over 30%, with significant spikes following the end of the MoU in 2019 and the onset of the pandemic in 2020. In terms of expenditure, antineoplastic and immunomodulation agents (category L) held the largest share, driven by the introduction of new, costly drugs. The expenditure per inhabitant revealed gender and age disparities, with older populations, particularly women, incurring higher costs. Geographically, drug expenditure, and consumption varied significantly, with distinct regional clusters identified. These clusters, while showing some overlap in consumption and expenditure patterns, also highlighted unique regional characteristics. Conclusions: The insights into prescription drug consumption and expenditure trends offer a valuable basis for developing targeted interventions aimed at optimizing healthcare resource allocation. Moreover, the findings underscore the importance of addressing regional and demographic disparities in pharmaceutical use, thereby contributing to more equitable and cost-effective healthcare strategies. More specifically, the age distribution of prescriptions shows the increase in younger ages, which, as a result, anticipates the overall increase in prescriptions. The knowledge of the most convex categories of medicine, as well as the percentages of the use of generic drugs, shows where interventions should be made, with financial incentives and information through new information channels. The geographic disparities recorded should lead to policies that help the residents of hard-to-reach areas to access prescriptions. In addition, the present study provides a strategic framework for policymakers and healthcare managers to guide future studies and inform decision-making processes. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation. Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. Key Messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies. [ABSTRACT FROM AUTHOR]

Background: High-dose cytarabine (HDAC) is commonly used for consolidation therapy in young acute myeloid leukemia (AML) patients, but the dosage of cytarabine is still controversial in the clinic due to its obvious post-chemotherapy adverse effects. The aim of this study was to contrast the efficacy in different dose groups of cytarabine after consolidation therapy in Chinese AML patients. Methods: AML patients treated with cytarabine consolidation at Qilu Hospital, Shandong University from January 2010 to September 2022 were retrospectively analyzed, from which 346 AML patients with relatively complete follow-up data were selected for this study. We compared the patients' overall survival (OS) rate, relapse-free survival (RFS) rate, and hematologic adverse events in terms of their general characteristics, cytarabine consolidation therapy dose, consolidation course, 2022 European Leukemia Net (ELN) risk stratification, and transplantation. Results: In AML patients under 60 years of age, the 5-year RFS rate with high-dose cytarabine consolidation therapy was superior to that of small-dose cytarabine (P = 0.024), while the 5-year RFS rate was comparable in the high-dose and intermediate-dose groups, and there was no obvious difference among the three groups in the 5-year OS rate (P > 0.05). OS and RFS of those given more than 3 courses of cytarabine consolidation therapy were better than those in the 1–2 courses group (P = 0.060, P = 0.040). OS and RFS were better in patients with cumulative dose of cytarabine ≥ 36g than in patients with cumulative dose < 36g (P < 0.05), but cumulative dose ≥ 54g was comparable in OS and RFS with ≥ 36–< 54g group (P > 0.05). There was no significant difference in hematologic adverse effects among the three treatment groups. In the latest ELN risk stratification favorable-risk group, the cumulative dose of cytarabine ≥ 36g had a better 5-year RFS rate than the < 36g group (P = 0.038), and in the intermediate-risk group the 5-year OS rate and RFS rate were better in the ≥ 36g group than the < 36g group (P = 0.012, 0.025). In addition, the prognosis of transplanted patients was better than that of non-transplanted patients, whereas in non-transplanted patients, consolidation therapy with ≥ 36g cytarabine can effectively improve outcomes. Multivariate analysis indicated that age, fibrinogen (FIB) and the cumulative dose of cytarabine of ≥ 36–< 54g were predictors of OS, while age, white blood cell (WBC) and HDAC were predictors of RFS. Conclusion: The results of the study showed that consolidation therapy with cytarabine up to a cumulative dose of ≥ 36–< 54g in AML patients who did not undergo transplantation significantly improved patient prognosis. In the latest ELN risk stratification, cumulative doses of cytarabine ≥ 36g had a better prognosis in favorable and intermediate-risk patients. [ABSTRACT FROM AUTHOR]

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1β in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines. [ABSTRACT FROM AUTHOR]

Akihiko Akamine,1 Yuya Nagasaki,2 Atsushi Tomizawa,2 Katsuya Otori2,3 1Department of Pharmacy, Doujin Hospital, Okinawa, Japan; 2Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan; 3Research and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, Kitasato University School of Pharmacy, Tokyo, JapanCorrespondence: Akihiko Akamine, Department of Pharmacy, Doujin Hospital, 1-37-12 Gusukuma, Urasoe, Okinawa, 901-2133, Japan, Tel +81-98-876-2212, Fax +81-98-874-7034, Email a-aka@kitasato-u.ac.jpPurpose: The risk factors for non-adherence to pharmacist or non-pharmacist explanations of preoperative medication discontinuation are unknown. The primary outcome of this study was to determine whether the final explainer’s occupation was a risk factor for non-adherence. The secondary outcomes were to determine the risk factors for non-adherence after limiting the departments or adjusting for age.Patients and Methods: We retrospectively examined the data (including patient age, sex, prescription medications, comorbidities, presence of roommate, and number of days between receiving explanation and surgery) of 1132 patients on medications that could affect surgery at a Japanese university hospital between April 1, 2017, and March 31, 2020. The primary endpoint was whether the occupation of the last person explaining medication discontinuation to the patient was an independent risk factor for non-adherence (age ≥ 65 years vs < 65 years). Secondary endpoints included subgroup analyses in urological, gastrointestinal, and otolaryngological areas, as well as a sensitivity analysis (age as a continuous variable) to confirm the validity of the primary endpoint results. A multivariate binary logistic regression identified independent non-adherence risk factors.Results: The main analysis showed that discontinuing two or more medications was a risk factor for non-adherence (adjusted odds ratio (AOR): 1.67; 95% confidence interval (CI): 1.13– 2.47; p = 0.01). However, in analyses coordinated by department (urological, gastrointestinal, and otolaryngological), ≥ 65 (versus < 65) years of age was determined as a risk factor for increased nonadherence (AOR: 2.27, 95% CI: 1.11– 4.63; p=0.024). Age-adjusted analysis (continuous variables) showed similar results to the primary endpoint (AOR: 1.68, 95% CI: 1.14– 2.49, p = 0.009).Conclusion: Two or more medications, and not the final explainer’s occupation, were associated with pre-surgery medication non-adherence. To prevent non-adherence, pharmacists and non-pharmacists should educate patients about preoperative medication discontinuation. These findings could help identify high-risk non-adherence patients.Plain Language Summary: At Kitasato University Hospital, pharmacists and non-pharmacists explain before surgery that patients scheduled for surgery should discontinue medications that could affect surgery. However, there are patients who fail to follow these explanations precisely, but the risk factors have not yet been identified. This study examined risk factors for patients who failed to comply with explanations from a pharmacist or non-pharmacist regarding the use of medications that could affect surgery. Risk factors were examined using a statistical method for identifying risk factors by considering patients’ age ≥ 65 (versus < 65) years, sex, the job title that explained the instructions to the patient, number of medications to be discontinued before surgery, and number of days between instructions and surgery as risk factors. Based on pharmacist/non-pharmacist explanations, the statistical analysis revealed that patients taking two or more medications that could affect surgery may be a risk factor for non-adherence to medications that should be discontinued before surgery. To improve medication adherence, pharmacists and non-pharmacists should be aware of the patient’s non-adherence risk factors, repeatedly explain them to the patient, and help the patient understand that failure to comply with the explanation increases surgical cancelation and intraoperative bleeding risks.Keywords: medication adherence, hematologic agents, pharmaceutical service

In vitro potency is one of the important parameters representing efficacy potential of drugs and commonly used as benchmark of efficacious exposure at early clinical development. There are limited numbers of studies which systematically investigate on how predictive in vitro potency is to estimate therapeutic drug exposure, especially those focusing on targeted anticancer agents despite the recent increase in approvals. This study aims to fill in such knowledge gaps. A total of 87 small molecule targeted drugs approved for oncology indication between 2001 and 2020 by the US Food and Drug Administration (FDA) were identified; relevant preclinical and clinical data were extracted from the public domain. Relationships between the in vitro potency and the therapeutic dose or exposure (unbound average drug concentration [Cu,av] as the primary exposure metrics) were assessed by descriptive analyses. The Spearman's rank correlation test showed slightly better correlation of the Cu,av (ρ = 0.232, p = 0.041) rather than the daily dose (ρ = 0.186, p = 0.096) with the in vitro potency. Better correlation was observed for the drugs for hematologic malignancies compared with those for solid tumors (root mean square error: 140 [n = 28] versus 297 [n = 59]). The present study shows that in vitro potency is predictive to estimate the therapeutic drug exposure to some extent, whereas the general trend of overexposure was observed. The results suggested that in vitro potency alone is not sufficient and robust enough to estimate the clinically efficacious exposure of molecularly targeted small molecule oncology drugs. The totality of data, including both nonclinical and clinical, needs to be considered for dose optimization. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications. Study Design Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial. The participants were treated with amisulpride for 4 weeks. Levels of complement and coagulation proteins at baseline were measured using both data-dependent and data-independent mass spectrometry approaches. The primary outcome was remission status at 4 weeks and the secondary outcomes included change in psychotic and functional symptoms over the period of treatment. In addition, immunoassays were performed at baseline for complement C1R, as well as for activation markers C4a and sC5b-9. Study Results The plasma level of complement variant C4A was significantly associated with remission at 4 weeks. Moreover, higher levels of several complement and coagulation pathway proteins were associated with a reduction in psychotic symptoms and an improvement in functioning. Immunoassays showed an association of baseline levels of C1R and C4a as well as complement activation marker sC5b-9 levels with treatment response. Conclusion The results demonstrated that the response to antipsychotic treatment might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is consistent with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these results inform the development of novel therapeutic approaches that target the complement system for psychosis. [ABSTRACT FROM AUTHOR]

An analysis of the range of antioxidant and hemostatic preparations registered in the Republic of Uzbekistan was carried out on the basis of information from the State Registers of Medicines, Medical Devices and Medical Equipment: 2019 No. 23, 2020 No. 24, 2021 No. 25. The sales volume of hemostatic drugs in the Uzbek market in 2019-2021 was studied based on DRUG AUDIT data. [ABSTRACT FROM AUTHOR]

Venetoclax is a novel agent used in hematologic malignancies. Although no long-term studies have directly implicated venetoclax, few studies show possible association with electrolyte abnormalities. Severe derangements in serum electrolyte levels can cause cardiac dysrhythmias, which can be potentially fatal. We present a case of venetoclax in association with the other medications causing life-threatening arrhythmias. Hypothesized mechanisms include damage to the distal tubules causing loss of potassium and magnesium. Our patient required modification of his medications and aggressive repletion of electrolytes with good outcomes. For patients on venetoclax, especially those with polypharmacy, caution should be exercised to prevent severe electrolyte derangements, which can lead to life-threatening arrhythmias. [ABSTRACT FROM AUTHOR]

Hematologic malignancies are lethal diseases arising from accumulated leukemic cells with substantial genetic or epigenetic defects in their natural development. Epigenetic modifications, including DNA methylation and histone modifications, are critical in hematologic malignancy formation, propagation, and treatment response. Both mutations and aberrant recruitment of epigenetic modifiers are reported in different hematologic malignancies, which regarding the reversible nature of epigenetic regulations, make them a potential target for cancer treatment. Here, we have first outlined a comprehensive overview of current knowledge related to epigenetic regulation's impact on the development and prognosis of hematologic malignancies. Furthermore, we have presented an updated overview regarding the current status of epigenetic-based drugs in hematologic malignancies treatment. And finally, discuss current challenges and ongoing clinical trials based on the manipulation of epigenetic modifies in hematologic malignancies. • HMAs like 5-azacytidine and Decitabine treat MDS and AML by causing DNA hypomethylation, but responses vary by dosage and mutations. • HDACis like Panobinostat, vorinostat, and valproic acid treat hematologic malignancies by promoting cell differentiation and apoptosis. • Combining epigenetic drugs with BCL2 inhibitors or HDACis with immune checkpoint inhibitors enhances treatment response in AML and lymphoma. • Targeting bromodomain proteins like BRD4 with BET inhibitors downregulates oncogenes, inducing apoptosis in various hematologic malignancies. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) acts on erythroid progenitor cells to promote their survival and differentiation to mature erythrocytes. Along with this canonical role, EPO is also reported to modulate energy metabolism, resulting in improved glucose tolerance and insulin sensitivity. EPO also stimulates the production of the hormone erythroferrone (ERFE) which acts to suppress hepcidin production, thus increasing dietary iron absorption and mobilizing stored iron for use in erythropoiesis. ERFE (initially termed myonectin) was also reported have an effect on systemic lipid metabolism by promoting the clearance of nonesterifed fatty acids (NEFA) from circulation. As increased levels of circulating NEFA blunt insulin sensitivity and impair glucose tolerance, ERFE-induced clearance of NEFA after EPO administration would have a beneficial effect on glucose metabolism. The aim of this study was to determine if the known metabolic effect of EPO treatment on glucose homeostasis is mediated by ERFE, produced in response to EPO. Mice lacking Erfe did not differ from wild-type mice in blood lipid parameters, blood glucose, and glucose or insulin tolerance at baseline or after chronic EPO treatment. Additionally, hepcidin suppression and the response of erythrocyte parameters to chronic EPO treatment were unaffected by the absence of Erfe. These findings suggest that the known beneficial effects of EPO on glucose metabolism are not attributable to an accompanying increase in ERFE production, and that Erfe is dispensable for normal glucose homeostasis. Furthermore, our data indicate that ERFE-independent mechanisms can suppress hepcidin in response to chronically elevated EPO levels.

Marzeptacog alfa (activated) (MarzAA) is an activated recombinant human FVII (rFVIIa) variant developed as subcutaneous (s.c.) administration for the treatment or prevention of bleeding episodes in patients with hemophilia A (HA) or hemophilia B (HB) with inhibitors and other rare bleeding disorders. Population pharmacokinetic (PK) modeling was applied for dose selection for a pivotal phase III clinical trial evaluating s.c. MarzAA for episodic treatment of spontaneous or traumatic bleeding episodes. The population PK model used MarzAA intravenous and s.c. data from previously completed clinical trials in patients with HA/HB with or without inhibitors. Based on the model, clinical trial simulations were performed to predict MarzAA exposure after different dosing regimens. The exposure target was identified using an exposure‐matching strategy with a wild‐type rFVIIa but adjusting for the difference in potency between the two compounds. Simulations demonstrated a sufficient absorption rate and prolonged exposure following a single 60 μg/kg dose leading to 51% and 70% of the population reaching levels above the target after 3 and 6 h, respectively. According to the phase III protocol, if a second dose was required after 3 h because of a lack of efficacy, 90% of the population was observed to be above target 6 h after the initial dose. The model‐informed drug development approach integrated information from several trials and guided dose selection in the pivotal phase III clinical trial for episodic treatment of an acute bleeding event in individuals with HA or HB with inhibitors without the execution of a phase II trial for that indication. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a common and unsolved problem in myelodysplastic syndrome (MDS) patients; we aimed to summarize the evidence of TPO-RA treatment for heath-related quality of life (HRQoL) and platelet transfusion burden of MDS patients. We searched Pubmed, Web of Science, EMBASE, and CENTRAL for randomized clinical trials (RCTs) comparing TPO-RA to placebo in MDS published until July 31, 2021. A random-effect model was used. Eight RCTs with 908 patients were identified. Only three RCTs involving eltrombopag reported HRQoL, and all three studies treated HRQoL as a secondary outcome. In these three RCTs, the HRQoL instruments used in each study were different. However, this outcome cannot be meta-analyzed because some studies did not provide complete data. Subsequent clinical trials should pay more attention to this. Compared to placebo, TPO-RA did not affect platelet transfusion incidence 0.83 (95% CI 0.60-1.15). There was no evidence for subgroup differences in the analyses of different types of TPO-RA, different additional agent, and different types of MDS risk groups. However, platelet transfusion units (RR = 0.68, 95% CI 0.53 to 0.84) were significantly decreased. The RR of patients who did not require platelet transfusion for 56 or more consecutive days was not different between groups (RR = 0.98, 95% CI 0.41 to 2.34). TPO-RA may decrease platelet transfusion units in MDS patients with thrombocytopenia. But the significance of this finding should be interpreted with caution, because too few studies were meta-analyzed. [ABSTRACT FROM AUTHOR]

Objectives: We primarily aimed to investigate the hematologic inflammatory parameters such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in patients with acromegaly. We also aimed to reveal the importance of these parameters in determining disease activity. Methods: The medical data of 535 patients with acromegaly were retrospectively reviewed. The sociodemographic characteristics, presence of comorbid disease, acromegaly-related clinical and medical treatment characteristics, insulinlike growth factor-1 and growth hormone levels at diagnosis, postoperative 3rd month and last visit, and hematologic inflammatory markers and indices at last visit were obtained from the patients' medical charts. The patients were divided into age-, sex-, and comorbid disease-matched four groups according to their last remission status: active disease, remission with only surgery, remission with medication, and discordant disease. Finally, a total of 290 patients were included. Results: We examined a total of 290 patients with acromegaly after primary therapy; 36 had active disease, 77 were in remission with only surgery, 129 were in remission with medication, and 48 had a discordant disease. When the patients were categorized by last remission status, the median MPV was higher in patients with discordant disease than in the remission group with only surgery, and there were no differences in terms of the NLR and PLR between groups. When the participants were divided into two groups according to the presence of remission at the postoperative 3rd month, patients who had remission had lower MPV levels than those who had not. However, the groups had similar features for the NLR and PLR. Conclusion: Our results, particularly those that reveal positive association between MPV and remission status, indicate that subclinical inflammation may play a role in increased mortality and morbidity. Therefore, in addition to patients with active disease, patients with discordant disease should be followed closely for cardiovascular risks. [ABSTRACT FROM AUTHOR]

C. odorata L. is considered to be a plant weed that is scattered in various climates. As a weed, this plant contains a variety of beneficial secondary metabolites. Several studies have shown the benefits of C. odorata L. leaf extract. This study reviews the metabolite content and the pharmacological activities of C. odorata L. leaf extract. A literature search was carried out to obtain various studies related to the use of this plant extract. Secondary metabolites identified in C. odorata L. are alkaloids, flavonoids, tannins, saponins, and steroids. Several reports have also shown that even though it is considered a weed, C. odorata L. leaf extract also provides many benefits due to its pharmacological activities. Various pharmacological activities include anti-inflammatory, anti-microbial, antioxidant, antidyslipidemia, hematologic agent, anti-diabetic and anti-cataract, analgesic and antipyretic, wound healing, anti-malaria, mosquito larvicidal, anti-hypercholesterolemia, and antifungal. [ABSTRACT FROM AUTHOR]

Bushen Jianpi Quyu Formula (BSJPQYF), an experienced formula, has been used to treat aplastic anemia (AA) more than three decades. To determinate the effect of BSJPQYF on AA, we constructed an immune-mediated AA mouse model. All mice were divided into four groups: control, model, low dose (0.85 g/mL), and high dose (1.7 g/mL BSJPQYF) group. They were administered with different concentrations of BSJPQYF or normal saline for 14 days. Besides, components of BSJPQYF were analyzed by electrospray ionization and mass spectrometry (ESI-MS). Subsequently, mouse peripheral blood and femurs were collected, and bone marrow mesenchymal stem cells (BMSCs) were isolated by fluorescence-activated cell sorting (FACS). Among them, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ) were measured by ELISA assay, PI3K, AKT, p-AKT, NF-κB, p-NF-κB, TNF-α, and cleaved caspase-3 proteins were detected by western blot. Compared with standard compounds, we identified three compounds of BSJPQYF, namely, icariin, kaempferol and tanshinone iia, as potentially effective compounds for the treatment of AA. Through an in vivo study, we found the administration of BSJPQYF in high dose for 14 days could significantly increase peripheral blood count and bone marrow (BM) cells, meanwhile decrease TNF-α, TGF-β, and IFN-γ levels. Besides, it could suppress the protein expression of PI3K and the phosphorylation of AKT and NF-κB to restrict the protein expression of TNF-α, eventually reduce the protein expression of cleaved caspase-3. This study demonstrated the therapeutic effects of BSJPQYF in AA, which could alleviate myelosuppression through inhibiting the expression of the PI3K/AKT/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

To test the usefulness of the Cancer and Aging Research Group (CARG) predictive tool, it was used to assess elderly cancer patients with prior anticancer therapy. Among patients with solid malignancies aged ≥ 65 years receiving second-line chemotherapy who were admitted to the Department of Medical Oncology/Hematology at Kakogawa Central City Hospital between April 2016 and September 2019, the risk ≥ grade 3 of developing chemotherapy-related adverse events (CRAEs) (low, intermediate, or high) was calculated using the tool. Correlations between grades 3 and 5 CRAE incidence rates in the first course of each regimen and CARG risk score, age, and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Included patients (n = 62) had a mean age of 71 years (range, 65–82 years). Severe CRAE incidence in patients with low, medium, or high CARG risk was 27%, 54%, and 71%, respectively (p = 0.026). The incidence of severe non-hematological toxicities was 5%, 35%, and 64%, respectively (p < 0.01). There was no association between age or ECOG PS and chemotherapy toxicity. The results suggest the validity of the CARG predictive tool in elderly cancer patients with prior anticancer therapy. Particularly, the tool showed potential for predicting non-hematological toxicity. [ABSTRACT FROM AUTHOR]

Introduction: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients. Methods: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records. Results: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day). Conclusion: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported. Case Presentation : A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia. Conclusion : When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient's condition. [ABSTRACT FROM AUTHOR]

Background and Objective: Due to the physiological changes caused by estrogen deficiency in menopause and due to the importance of aerobic exercise as one of the non-pharmacological strategies to improve these changes, the present study was performed to evaluate the effect of moderate-intensity aerobic exercise on lipid profile and the number of some plasma blood cells after ovariectomy. Methods: This experimental study was performed on 40 female rats that were divided into two equal groups and one group underwent ovariectomy. After two weeks of recovery, the rats were randomly divided into four groups: control-healthy, control-ovariectomy, exercise-healthy and exerciseovariectomy. The rats exercised for 25 weeks with 25 meter per minute intensity and blood samples were taken 48 hours after the last training session. Findings: Ovary removal in the control-ovariectomy group increased body weight (240.20±11.37) compared to the healthy-control group (198.36±6.79) (p=0.01), increased triglyceride (82.33±12.38) compared to control-healthy (36.83±3.55) (p=0.01), increased total cholesterol (130.66±3.82) compared to healthy-control (95.5±1.33) (p=0.0001) and increased monocytes (3.73±0.58) compared to the control-healthy (0.233±0.06) (p=0.0001). Ovariectomy caused an increase in white blood cells in the control-ovariectomy group (6.33±1.39) compared to the healthy-exercise group (3.68±0.74) (p=0.05). Total cholesterol levels decreased in exercise-ovariectomy (108±3.53) compared to control-ovariectomy (130.66±3.82) (p=0.001). Eight weeks of aerobic exercise reduced monocytes in the exercise-ovariectomy group (0.268±0.03) compared to the control-ovariectomy group (3.73±0.58) (p=0.001). Conclusion: The results of the study showed that ovariectomy increased inflammation due to an increase in white blood cells, monocytes and platelets, and aerobic exercise was able to partially compensate for these changes in lipid and hematological parameters resulting from ovary removal. It seems that aerobic exercise can improve the effects of ovariectomy on white blood cells and platelets after adaptation, which has a significant positive effect on body weight and lipid profile. [ABSTRACT FROM AUTHOR]