Imetelstat: Finally a disease-modifying treatment for lower-risk myelodysplastic syndromes?

Favorable results were achieved in a phase 3 clinical trial (IMerge) with the telomerase inhibitor imetelstat in transfusion-dependent patients with lower-risk myelodysplastic syndromes (MDSs) who relapsed or were refractory to erythropoiesis-stimulating agents.1 Imetelstat is likely to become a useful addition to our limited therapeutic options for patients with MDS.

The relationship between cardiological parameters and PCR in patients with coronavirus infection: A cross-sectional study.

Cardiovascular injuries induced by SARS CoV-2 have been reported repeatedly in various studies. Therefore, it is necessary to understand cardiac complications at a low cost, quickly. This study aimed to determine the relationship between cardiological parameters and polymerase chain reaction (PCR) in patients with coronavirus infection. : Patients who were admitted to the emergency department due to the ongoing pandemic, all patients with similar symptoms to coronavirus disease 2019 infection were initially admitted to the respiratory emergency room and underwent subsequent evaluations to confirm or rule out SARS-COV2 infection symptoms were assessed for eligibility. Patient were categorized into 2 groups 1. Positive PCR and negative PCR groups. Binary logistic regression was performed to assess the effect of several factors on the likelihood of developing positive troponin, reduced ejection fraction (EF), and Positive brain natriuretic peptide (BNP). Among 195 patients included, 115 (58.9%) had positive PCR. Patient in the positive PCR and negative PCR were 58.04 ±â€…18.03 and 59.19 ±â€…15.38 years of age, respectively. Patients in the "positive PCR" were significantly less likely to have chronic kidney disease (6.69% vs 17.5%, P value: .022), consume calcium channel blockers (6.69% vs 18.75%, P value:0.012). At the univariable level, positive PCR was significantly associated with fewer odds for positive BNP (OR:0.46, P = .019); nevertheless, the association was no longer significant after adjusting for confounders (adjusted OR:0.56, P = .158). Unadjusted positive PCR results were not found to have a significant association with positive troponin or reduced EF. Likewise, multivariable regression revealed no association between positive PCR and positive troponin (aOR:1.28, P = .529) and reduced EF (aOR:0.65, P = .369). PCR positivity did not result in positive troponin and BNP and did not appear to decrease EF. In other words, serial troponin and BNP checks and initial echocardiography in coronavirus disease 2019 respiratory emergencies do not make significant differences in diagnostic and therapeutic management and inpatient outcomes of patients with positive or negative PCR and are not specific findings. Evidence suggests some coronavirus-induced cardiac complications will be manifested in the long term.

The incidence of myopericarditis in patients with COVID-19.

Introduction: SARS-COV-2 can affect different organ systems, including the cardiovascular system with wide spectrum of clinical presentations including the thrombotic complications, acute cardiovascular injury and myopericarditis. There is limited study regarding COVID-19 and myopericarditis. The aim of this study was to evaluate myopericarditis in patients with definite diagnosis of COVID-19. Methods: In this observational study we analyzed the admitted patients with definite diagnosis of COVID-19 based on positive RT-PCR test. Laboratory data, and ECG changes on days 1-3-5 were analyzed for sign of pericarditis and also QT interval prolongation. Echocardiography was performed on days 2-4 and repeated as necessary, and one month after discharge for possible late presentation of symptom. Any patient with pleuritic chest pain, and pericardial effusion and some rise in cardiac troponin were considered as myopericarditis. Results: A total of 404 patients (18-90 years old, median = 63, 273 males and 131 females) with definite diagnosis of COVID-19 were enrolled in the study. Five patients developed in-hospital pleuritic chest pain with mild left ventricular dysfunction and mild pericardial effusion and diagnosed as myopericarditis, none of them proceed to cardiac tamponade. We found no case of late myopericarditis. Conclusion: Myopericarditis, pericardial effusion and cardiac tamponade are rare complication of COVID-19 with prevalence about 1.2 %, but should be considered as a possible cause of hemodynamic deterioration.

The Protective Effects of L-Carnitine and Zinc Oxide Nanoparticles Against Diabetic Injury on Sex Steroid Hormones Levels, Oxidative Stress, and Ovarian Histopathological Changes in Rat.

Diabetes mellitus is a common chronic metabolic disorder. This study aimed to investigate the effects of co-treatment with L-carnitine (LC) and zinc oxide nanoparticles (ZnONPs) on serum levels of sex hormones, oxidative stress, and ovarian histopathology in streptozotocin (STZ)-induced diabetic rats. Female Wistar rats (n = 56, 180-220 g) received a single intraperitoneal (IP) injection of STZ (65 mg/kg). They were randomly assigned into the following groups: diabetic group (Dia), Dia+Met group (100 mg metformin/kg/day), Dia+LC group (200 mg/kg/day), Dia+ZnONPs group (10 mg/kg/day), and Dia+LC+ZnONPs group (200 mg LC/kg/day and 10 mg ZnONPs/kg/day). Control group (Ctl) received the same volume of STZ solvent. After 21 days of treatment, blood serum was centrifuged for sex hormone assays. The right ovary was used for biochemical analysis, and the left ovary was fixed in 10% neutral buffered formalin for histological assessment. The levels of estradiol, progesterone, FSH, and LH significantly increased in the Dia+ZnONPs+LC group (P < 0.001) compared with the Dia group. Co-treatment with LC and ZnONPs reduced malondialdehyde and carbonyl protein and increased glutathione, catalase, and superoxide dismutase activities in ovarian tissue compared with the Dia group (P < 0.05). Moreover, the number of all ovarian follicles significantly increased in this group compared with the Dia group (P < 0.05). The results of this study indicated that co-treatment with LC and ZnONPs could preserve ovarian function by increasing sex hormones levels and antioxidant activity and decreasing lipid peroxidation in diabetic rats. Therefore, this compound supplementation may improve ovulation and fertility in people with diabetes mellitus.

Systemic effects of starved fibroblast culture supernatant on immunosuppressed rats treated with cancer stem cells (LA7).

BACKGROUND: The present study aimed to investigate and compare the effect of starved fibroblast culture supernatant (SFS), DMEM and normal saline alone or along with LA7 on dexamethasone-treated immunosuppressed Wistar rats. METHODS: After the isolation of fibroblasts from the fresh foreskin of children, it was cultured in serum-free DMEM, and the supernatant collected after 16 hours (16h-SFS). This solution and the other treatments were injected subcutaneously into the rats from each group once daily for 14 days. The liver, intestine and lung histology along with blood cellular and biochemical characteristics were studied. RESULTS: The results showed that dexamethasone as immunosuppressant reduced the body weight. The histological change in the liver was mild fibrosis induced by LA7+16h-SFS. Also, among the different blood cellular and biochemical indices measured, the eosinophil percentage in the 16h-SFS treated rats , glucose levels in the 16h-SFS+LA7 group and triglyceride concentrations in the 16h-SFS group were changed (p<0.05). CONCLUSION: This study showed that the secretions of starved fibroblasts especially that combined with LA7 cancer stem cells could induce some minor histological and biochemical changes in immunosuppressed rats, and also it opened a new window for subsequent investigations on unknown mechanisms related to this work.

Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study.

Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.

Differentiation of human umbilical cord mesenchymal stem cell into germ-like cell under effect of co-culture with testicular cell tissue.

Supplements produced by mouse testicular cells (mTCs) and the interaction between cells can increase the differentiation rate of human umbilical cord mesenchymal stem cells (hUCMSCs) into the germ-like cells. We studied the differentiation rate of hUCMSCs into the germ-like cells under effect of mTCs co-culturing. Isolated hUCMSCs from postpartum human umbilical cords were cultured. Then, the expression of mesenchymal (CD73, CD90 and CD105) and haematopoietic (CD34 and CD45) markers of hUCMSCs were confirmed by flow cytometry. Then, the hUCMSCs were cultured in four distinct groups: (a) control, (b) co-culture until D0, (c) co-culture until D5 and (d) co-culture until D10, in order to differentiate into the germ-like cells. After 10 days, the expression of OCT4, VASA, Fragilis and SYCP3 genes were examined by Real-Time qPCR. The flow cytometry indicated a high expression of mesenchymal markers and a low expression of haematopoietic markers (CD73:98.6%, CD90: 99.1%, CD105: 99.5%, CD34: 4.22% and CD45: 2.54%). The expression of OCT4 decreased during the time while the expression of VASA, Fragilis and SYCP3 markers increased in the co-culture with testicular cells (p value <.05). Co-culture with mTCs may be used as an effective method to differentiate hUCMSCs into germ-like cells.

Cohort Profile Update: The Amirkola Health and Ageing Project (AHAP).

The original cohort study of AHAP started in 2011 on 1616 elderly residents of Amirkola, northern part of Iran near the Caspian Sea. The main goal of this study was to comprehensively evaluate the health of the elderly in the region with the emphasis on chronic diseases such as osteoporosis. The first cohort profile was published in the International Journal of Epidemiology in 2014. The phase 1 AHAP showed the elevated level of some diseases and conditions including osteoporosis, metabolic syndrome, obesity, vision problems and relatively low levels of oral health. Therefore, the second phase of this cohort started with more complete population coverage in 2016, not only to collect and record the information based on previous protocol, but also consider new areas such as nutritional status, complete eye and dental examinations and health assessment on the basis of Iranian Traditional Medicine. The new aspect of this project is to conduct clinical and laboratory examinations at the health center to extend more facilities to the elderly. In addition to serum and DNA, samples of saliva, hair and nails are collected and kept under standard conditions in the biobank of this cohort. Researchers can apply for access to data or suggest a collaborative study by submitting the proposal to AHAP committee.

Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis.

New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first-line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first-line treatment including induction therapy, cytotoxic stem cell mobilization and high-dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34(+) HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long-term HSPC proliferation in vitro. We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF-ß signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long-term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF-ß signaling pathway.