Platelet transfusion enhances pro-aggregatory status shortly after coronary artery bypass grafting (CABG while modulating platelet pro-inflammatory state 1-week post-surgery.

During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study investigates the effects of platelet transfusion on the major pro-aggregatory, pro-inflammatory and immunomodulatory markers of platelets. Platelets from 20 patients, 10 who received platelet transfusion and 10 without, were subjected to flow cytometery where P-selectin and CD40 ligand (CD40L) expressions and PAC-1 binding (activation-specific anti GPIIb/GPIIIa antibody) analysed at five-time points of 24 h before surgery, immediately, 2 h, 24 h and 1 week after surgery. Analysis of intra-platelet transforming growth factor-beta-1 (TGF-ß1) was also conducted using western blotting. Patients with platelet transfusion showed increased levels of P-selectin, CD40L and intra-platelet TGF-ß1 2-h after surgery compared to those without transfusion (p < 0.05). PAC-1 binding was increased 24 h after surgery in transfused patients (p < 0.05). Given the significant post-transfusion elevation of platelet TGF-ß1, P-sel/CD40L reduction in transfused patients a week after was of much interest. This study showed for the first time the significant effects of platelet transfusion on the pro-inflammatory, pro-aggeregatory and immunomodulatory state of platelets in CABG patients, which manifested with immediate, midterm and delayed consequences. While the increased pro-inflammatory conditions manifested as an immediate effect of platelet transfusion, the pro-aggregatory circumstances emerged 24 h post-transfusion. A week after surgery, attenuations of pro-inflammatory markers of platelets in transfused patients were shown, which might be due to the immunomodulatory effects of TGF-ß1.

Coronary artery bypass grafting (CABG) induces pro-inflammatory and immunomodulatory phenotype of platelets in the absence of a pro-aggregatory state.

BACKGROUND: Coronary artery bypass grafting (CABG) is considered the choice treatment for patients suffering from coronary artery disease (CAD). In the inflammatory milieu of cardiopulmonary bypass (CPB), systemic inflammatory response syndrome (SIRS) can induce a platelet pro-inflammatory state which could exacerbate post-CABG inflammatory status while affecting hemostatic function in patients. Therefore, focusing on platelets, the study presented here attempted to evaluate the pro-inflammatory and immunomodulatory profile of platelets as well as pro-aggregatory status during CABG. METHODS: Platelets from patients undergoing CABG were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding in five intervals of 24 h before surgery, immediately, 2 h, 24 h, and one week after surgery. Moreover, intra-platelet TGF-ß1 was also examined with western blotting. RESULTS: Data showed increases of P-selectin and CD40L expressions in patients, with the meaningful loss of platelet contents of TGF-ß1 after CABG (p < 0.001), where the changes tended to recover by day 7 of surgery while remaining above baseline (p < 0.001). Meanwhile, no significant change in PAC-1 binding capacity was shown. CONCLUSION: The study presented here suggests that although the release of pro-inflammatory substances from platelets during CABG supports the post-operative inflammatory state, platelets are not pro-aggregatory enough to enhance thrombotic events after surgery. Whilst these observations could be due to successful medical interventions to optimize hemostasis during and after surgery, post-CABG reversal of anticoagulant by protamine is considered as another factor that may also have contributed to preventing pro-aggregatory but not pro-inflammatory and immunomodulatory functions of platelets.

Lower Levels of TET2 Gene Expression, with a Higher Level of TET2 Promoter Methylation in Patients with AML; Evidence for the Role of Aberrant Methylation in AML Pathogenesis.

DNA methylation is a key epigenetic mechanism that is dysregulated in leukemia and plays a significant role in leukemogenesis. Ten-eleven translocation 2 (TET2) is one of the most frequently mutated genes among the DNA methylation regulators in hematologic malignancies, indicating its tumor-suppressor function. In this study, we investigated the expression and methylation status of TET2 in patients with AML. Quantitative RT-PCR was used to evaluate TET2 expression in peripheral blood mononuclear cells (PBMCs) from 51 newly diagnosed AML patients and 50 healthy controls. The methylation-sensitive high-resolution melting (MS-HRM) method was used in 45 patients with AML and 15 healthy controls to evaluate the promoter methylation of TET2. TET2 expression was significantly downregulated (P < 0.0001) in patients with AML compared to that in healthy controls. Furthermore, the methylation level of the TET2 promoter was significantly different between patients and controls. Aberrant methylation of the TET2 promoter was observed in 53.3% of the patients. Interestingly, a negative (- 0.3138) and significant (P = 0.0358) correlation between TET2 methylation and expression was found. The survival of patients with downregulated TET2 was poorer than that of other patients. TET2 gene expression was significantly downregulated while the promoter methylation was higher in patients, indicating that TET2 may be a tumor suppressor gene and a prognostic factor in AML and that transcriptional silencing of the TET2 gene may play a role in AML pathogenesis. Since epigenetic mechanisms are reversible, abnormal TET2 methylation could become a therapeutic target in the future.

Stable CAD patients show higher levels of platelet-borne TGF-ß1 associated with a superior pro-inflammatory state than the pro-aggregatory status; Evidence highlighting the importance of platelet-derived TGF-ß1 in atherosclerosis.

Activated platelets are involved in the atherogenic stage of atherosclerosis, while they can also progress it to atherothrombosis which may cause an ischemic state and organ failure. In general, coronary artery disease (CAD) is considered as common and severe clinical consequence of atherosclerosis, manifesting as a chronic inflammatory condition with the release of platelet mediators, among which the importance of platelet-borne TGF-ß1 is not yet well understood. Hence, for the first time, this study aimed to examine platelet level of TGF-ß1 (latent/mature) in CAD-patients and its association with the expression of platelet pro-inflammatory molecules. Platelet from stable CAD-patients candidate for CABG and healthy controls were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding. Platelet-borne and soluble TGF-ß1, both mature/active and latent forms were also examined with western blotting. Higher expression levels of P-selectin and CD40L in patients with CAD than in controls were associated with comparable levels of PAC-1 binding in both groups. Platelet TGF-ß1 levels were also significantly higher in patients, while their platelets showed clear bands of mature TGF-ß1 that were barely visible in healthy individuals. Soluble TGF-ß1 was also higher in patients. Significant correlations between mature/active TGF-ß1 and platelet pro-inflammatory markers (P-selectin and CD40L) as well as common indicators of inflammation (CRP and ESR) were observed in CAD patients. In this study, given the insignificant changes in pro-aggregatory potentials in stable CAD, the pro-inflammatory state of platelets may be more involved in disease development and progression. Direct correlations between active platelet-borne TGF-ß1 and pro-inflammatory markers with its presence in CAD-patients, which was almost absent in the platelets of healthy individuals, may also underscore the significant contribution of platelet-borne TGF-ß1 to the pathogenesis of the disease.

Platelet-leukocyte crosstalk in COVID-19: How might the reciprocal links between thrombotic events and inflammatory state affect treatment strategies and disease prognosis?

Platelet-leukocyte crosstalk is commonly manifested by reciprocal links between thrombosis and inflammation. Platelet thrombus acts as a reactive matrix that recruits leukocytes to the injury site where their massive accumulation, activation and migration promote thrombotic events while triggering inflammatory responses. As a life-threatening condition with the associations between inflammation and thrombosis, COVID-19 presents diffuse alveolar damage due to exaggerated macrophage activity and cytokine storms. These events, together with direct intracellular virus invasion lead to pulmonary vascular endothelialitis, cell membranes disruption, severe endothelial injury, and thrombosis. The developing pre-alveolar thrombus provides a hyper-reactive milieu that recruits circulating leukocytes to the injury site where their activation contributes to thrombus stabilization and thrombosis propagation, primarily through the formation of Neutrophil extracellular trap (NET). NET fragments can also circulate and deposit in further distance where they may disseminate intravascular thrombosis in severe cases of disease. Thrombi may also facilitate leukocytes migration into alveoli where their accumulation and activation exacerbate cytokine storms and tissue damage, further complicating the disease. Based on these mechanisms, whether an effective anti-inflammatory protocol can prevent thrombotic events, or on the other hand; efficient antiplatelet or anticoagulant regimens may be associated with reduced cytokine storms and tissue damage, is now of interests for several ongoing researches. Thus shedding more light on platelet-leukocyte crosstalk, the review presented here discusses the detailed mechanisms by which platelets may contribute to the pathogenesis of COVID-19, especially in severe cases where their interaction with leukocytes can intensify both inflammatory state and thrombosis in a reciprocal manner.

A new method of "student-centered formative assessment" and improving students' performance: An effort in the health promotion of community.

BACKGROUND: Improving the learning process in education will empower medical students, and also formative assessment helps improve the teaching-learning process by providing ongoing reflective information about learning gaps. OBJECTIVE: The aim of this study was to explore the effect of student-centered formative assessment by weekly reflective self-correction quizzes on medical laboratory students' performance on the final examination of hematology course in 2018. MATERIALS AND METHODS: A semi-experimental study was conducted on fifty students divided randomly into intervention (n = 25) and control groups (n = 25) using convenience sampling in 2018 from Torbat Heydariyeh University of Medical Sciences, Iran. Data analysis was performed using SPSS software version 16, two-sample t-test, Chi-square test, and analysis of covariance. RESULTS: The intervention had positive effects on students' mean test scores in hematology II so that the intervention and control groups managed to obtain 18.45 ± 1.46 and 14.57 ± 2.64, respectively (P < 0.01). CONCLUSIONS: The results suggested that weekly formative assessments along with reflective self-correction activity and active participation of students in the learning process by designing questions could improve student learning.

Optimal Design of Air Quality Monitoring Network and its Application in an Oil Refinery Plant: An Approach to Keep Health Status of Workers.

BACKGROUND: Industrial air pollution is a growing challenge to humane health, especially in developing countries, where there is no systematic monitoring of air pollution. Given the importance of the availability of valid information on population exposure to air pollutants, it is important to design an optimal Air Quality Monitoring Network (AQMN) for assessing population exposure to air pollution and predicting the magnitude of the health risks to the population. METHODS: A multi-pollutant method (implemented as a MATLAB program) was explored for configur-ing an AQMN to detect the highest level of pollution around an oil refinery plant. The method ranks potential monitoring sites (grids) according to their ability to represent the ambient concentration. The term of cluster of contiguous grids that exceed a threshold value was used to calculate the Station Dosage. Selection of the best configuration of AQMN was done based on the ratio of a sta-tion's dosage to the total dosage in the network. RESULTS: Six monitoring stations were needed to detect the pollutants concentrations around the study area for estimating the level and distribution of exposure in the population with total network efficiency of about 99%. An analysis of the design procedure showed that wind regimes have greatest effect on the location of monitoring stations. CONCLUSION: The optimal AQMN enables authorities to implement an effective program of air quality management for protecting human health.

Intrasphincteric botulinum toxin injection in treatment of chronic idiopathic constipation in children.

OBJECTIVE: Injection of botulinum toxin into the anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. The purpose of this study was to determine the utility of intra sphincteric injection of botox in the treatment of children with refractory constipation. METHODS: All children who suffered from chronic constipation for more than three months, and who had not responded to medical treatment, were referred to pediatrics surgical clinic for surgical intervention by pediatric gastroenterologist. The patients were randomly divided into cases and control group. The control group received no injection and was only treated with stool softeners. The case group received this therapy in addition to injection. After the botox injection, patients were asked about the presence of the signs of constipation including painful defecation, vomiting, stool consistence, soiling and defecation interval. FINDINGS: Defecation of painful stool existed in 88% of patients before botox injection and it was reduced to 15% after botox injection. In the control group, 90% of patients had painful defecation, which reduced to 86% after medical treatment (P=0.0001). Stool was hard in 80% of patients before was reduced to 28% after botox injection. In the control group, it existed in 81% of children and reduced to 78% after medical treatment (P=0.0001). Soiling existed in 62% of patients before and was reduced to 8% after botox injection, but in the control group it reduced from 62% to 42.5% after medical treatment (P=0.0001). In the control group, 98% of the patients had defecation intervals more than 3 days and it was the same after medical treatment. In case group, this index before botox injection was 9.1 days, and after botox injection was reduced to 2.6 days (P=0.0001). CONCLUSION: Our study results showed that injection of botulinum toxin into anal sphincter is an effective and safe new treatment of chronic idiopathic constipation in children.

Retroperitoneal fibrosis as a result of signet ring cell gastric cancer: a case-based review.

BACKGROUND: Retroperitoneal fibrosis is a rare and obvious condition in the abdominopelvic cavity. Signet ring cell carcinoma of the stomach with gross appearance of linitis plastica is another rare association. CASE PRESENTATION: We present a rare case of a 49-year-old woman presenting with persistent nausea and vomiting for 20 days. Three months ago, she was admitted with severe flank pain and was referred to the urology service. She was placed with stents for strictures in both ureters. She underwent endoscopy for heartburn, melena, dyspepsia, and weight loss (7 kg/5 month), which revealed congestion of the mucosa of the fundus and body with fine linear erosion and decreased distensibility of the stomach suggesting linitis plastica. A biopsy indicated full-thickness infiltration by signet ring cell gastric cancer. A CT scan showed evidence of retroperitoneal fibrosis with large lymph nodes around the aorta. CONCLUSION: This paper shows that the gastric linitis plastica can present with many deceptive clinical presentations, raising the risk of postponed diagnosis.

Incidence of malignancy after living kidney transplantation: a multicenter study from iran.

Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation.

Infantile hepatic hemangioendothelioma: report of a case with fine needle aspiration findings.

BACKGROUND: Infantile hepatic hemangioendothelioma is a rare tumor. Cytologic and histologic differentiation from other hepatic tumors is necessary to determine appropriate therapy. Fine needle aspiration cytology of this rare tumor has not been reported in the literature before. CASE: A 5-month-old female infant presented with hepatomegaly. Computed tomography revealed numerous nodules occupying the entire liver parenchyma that were considered to be metastatic tumors. However, the primary tumor was not detected. Cytology smears revealed numerous clusters of and isolated, benign-looking, cuboidal, round cells that were diagnosed as benign tumors, and a laparotomy was advised. Histology of the nodules showed infantile hepatic hemangioendothelioma. The patient is alive and undergoing supportive therapy. CONCLUSION: A vascular lesion should be considered in a fine needle aspiration biopsy of liver masses in infants, especially when the clinical features are not consistent with a metastatic malignancy. Immunoreactivity for factor VII-related antigen, CD34 and cytokeratin-7 is helpful in establishing the diagnosis.

Pulmonary metastatic calcification in a leukemic patient: a case report.

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children and accounts for 80% to 85% of cases. Hypercalcemia-associated pulmonary calcification has been observed in ALL, but overall it is a rare condition. Hereby, we wanted to report a case of pulmonary metastatic calcification in a 4-year-old girl with diagnosis of ALL in our center, who died 1 year after diagnosis of leukemia. Pulmonary infiltrates were seen 2 months after diagnosis of leukemia, which was proved to be the flecks of calcium in alveolar spaces after open-lung biopsy performed 4 months after diagnosis of ALL, but elevated serum calcium was detected late in the course of the disease (7 mo after lung biopsy), this late occurrence of hypercalcemia is not reported yet.