Comparison of faecal protein biomarkers' diagnostic accuracy for colorectal advanced neoplasms: a systematic review and meta-analysis.

Early diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis.

The rate of aerobic glycolysis is a pivotal regulator of tumor progression.

PURPOSE: Cancer cells depend on glucose metabolism via exclusive glycolysis pathway is named Aerobic glycolysis or Warburg effect. The aim of this study was investigation of different glucose accessibility conditions on the rate of Warburg effect and its impact on Hypoxia inducible factors-1 α (HIF-1 α)/vascular endothelium growth factor (VEGF) pathway in breast cancer cells lines. METHODS: MDA-MB-231 (Warburg phenomenon) and MCF-7 (oxidative) cell lines were cultured in DMEM and exposed to three different glucose accessibility medium for 48 h (5.5 mM as normal glucose (NG), 25 mM as high glucose (HG) and 2-Deoxyglucose (2-DG) as restricted glucose accessibility). Glucose uptake, intra/extracellular lactate and pyruvate, HIF-1α accumulation and vascular endothelium growth factor (VEGF) expression were evaluated by standard methods. RESULTS: Our results showed in NG condition both of cell lines produce lactate, but it was higher in MDA-MB-231. HG condition increased extracellular lactate in both cell lines especially in MCF-7 cells whereas intracellular lactate and pyruvate raised only in MCF-7. 2-DG decreased extracellular and intracellular lactate and pyruvate in both cell lines especially in MDA-MB-231. HIF-1α accumulation was detectable in NG condition in both cell lines. HG condition increased HIF-1α accumulation in MCF-7 cells but not in MDA-MB-231 and 2-DG decreased it in both call lines, especially in MDA-MB-231. Expression of VEGF had similar pattern with HIF-1α in different conditions. CONCLUSIONS: Our findings revealed the rate of Warburg effect is an important indicator for tumor promotion and invasion due to its impacts on important transcription factors like HIF-1α.

Prognostic Accuracy of Cardiovascular Disease Biomarkers in Patients with COVID-19: A Diagnostic Test Accuracy Meta-Analysis.

Background: Several reports have determined that cardiovascular diseases (CVDs) are common complications in patients with coronavirus disease 2019 (COVID-19) and lead them to poor outcomes. CVD biomarkers have, thus, great potential to be used as prognostic biomarkers. We aimed to determine the accuracy of CVD biomarkers for the prognosis of the COVID-19 patient's outcome via a diagnostic test accuracy (DTA) meta-analysis. Methods: Until September 30, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to obtain related papers. The summary points and lines were calculated using bivariate/HSROC model. As outcomes, we considered critical conditions and mortality. Results: A total of 17 659 patients from 33 studies were included. Five biomarkers, namely increased levels of lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase (CK), D-dimer, and thrombocytopenia, met the inclusion criteria. Our results indicated that LDH and cTnI had good accuracy for the prognosis of critical condition (AUCHSROC=0.83 and 0.80, respectively), while LDH, cTnI, and D-dimer had acceptable accuracy (AUCHSROC=0.74, 0.71, and 0.72, respectively) for the prognosis of mortality. LDH and D-dimer had high sensitivity, whereas cTnI had high specificity. The other biomarkers did not have acceptable accuracy. Significant publication bias was found for D-dimer (P=0.053). Conclusion: Among CVD biomarkers, LDH and cTnI had good accuracy for the prognosis of critical outcomes and acceptable accuracy for the prognosis of mortality, without publication bias. Given their different sensitivities and specificities, we recommend the use of these 2 biomarkers concomitantly.

Procalcitonin Has Good Accuracy for Prognosis of Critical Condition and Mortality in COVID-19: A Diagnostic Test Accuracy Systematic Review and Meta-analysis.

Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient's outcome by a DTA meta-analysis. Until August24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical condition.

High Glucose-reduced Apoptosis in Human Breast Cancer Cells Is Mediated by Activation of NF-κB.

Tumor cells rely on glycolysis for their energy supply with the production of lactate even in normoxia condition, which is named aerobic glycolysis or Warburg effect. Therefore, high glucose (HG) concentration provides a favorable condition for increasing proliferation, angiogenesis and decreasing apoptosis, but its molecular mechanisms are still unknown. The objective of this study is to investigate HG condition on tumor cells behavior including proliferation, apoptosis, and an angiogenesis mediator. In this study, MCF-7 derived from human breast adenocarcinoma, were cultured in DMEM with two different concentrations of glucose for 48 h (5.5 mM as normal glucose (NG) condition and 25 mM as HG condition). We used Zingiber officinale extraction for the inhibition of NF-κB. Cell proliferation assay was done by direct counting, cell viability by MTT method, bcl-2 by Immunocytochemistry, apoptosis by Hoechst/PI double staining and vascular endothelium growth factor (VEGF) by ELISA. Results showed that HG increased lactate production, significantly. HG increased cell proliferation, cell viability, VEGF secretion, and bcl-2 expression while it decreased apoptosis. However, when HG was combined with Zingiber officinale extraction, cell proliferation, cell viability, VEGF secretion and bcl-2 expression decreased and apoptosis increased significantly due to inhibition of NF-κB. Results revealed that HG increased cell proliferation, angiogenesis and decreased apoptosis due to activation of NF-κB pathway. Moreover, the probable mechanism of the activation of NF-κB in HG is increasing reactive oxygen species (ROS) in this condition that can activate NF-κB directly.

Sex Hormones and Prolactin Levels and Their Association with Anti Cardiolipin Antibody in Patients with Systemic Lupus Erythematosus.

Pathogenesis of systemic lupus erythematosus (SLE) is complex and multi-factorial. Among various suggested mechanisms for the disease, the hormonal theory has been considered as one of the most important mechanisms. Recently, the association of sex hormones with manifestations of antiphospholipid antibody syndrome (APLS) has been hypothesized. The aim of present study was to assess the serum levels of anticardiolipin antibody (ACA), sex hormones and prolactin in SLE female patients and their association with the disease. This study comprised 40 SLE female patients and 41 healthy age-matched female subjects. For all patients and controls, the serum levels of ACA (IgG and IgM), estradiol, testosterone, progesterone, dehydroepiandrosterone sulfate (DHEA-S) and prolactin were measured by ELISA method. Our study revealed that serum levels of testosterone, DHEA-S and progesterone were significantly lower in SLE patients than control (p<0.001). However, serum levels of estradiol and prolactin were significantly higher in SLE patients compared to controls (p<0.001). There was a significant difference between mild and moderate severity patients group for ACA positivity (95% CI 13.67-41.3; p=0.03). Also, SLE patients with positive ACA showed significantly lower (p<0.001) serum levels of testosterone, DHEA-S and progesterone and significantly higher (p<0.001) estradiol and prolactin serum levels compared to negative ACA patients. The results of our study indicated that expression and metabolism of sex hormones and prolactin are different in female SLE patients compared to healthy subjects. It seems, change in serum levels of these hormones is related to higher SLE disease activity, increased thrombotic risks and increased renal involvement.

The prevalence of anemia and hemoglobinopathies in the hematologic clinics of the kermanshah province, Western iran.

Hemoglobinopathies are the most common single gene disorders worldwide with a considerable frequency in certain area particularly Mediterranean and Middle Eastern countries. Hemoglobinopathies include structural variants of hemoglobin (Hb S, Hb C, HbE,…) and thalassaemias which are inherited defects in the globin chains synthesis. The present study was conducted to determine the prevalence of hemoglobinopathies in western Iranian patients. A total of 344 patients (151 males and 193 females) with abnormal CBC and/or hemoglobin electrophoresis were enrolled in the present study. Cellulose acetate gel electrophoresis was performed for all patients and abnormal bands were identified by citrate agar gel electrophoresis and PCR based methods. Iron deficiency anemia (IDA) was present in 156 (45.3%) individuals. Thirty four (9.8%) patients had both iron deficiency anemia and α-thalassemia trait trait, 41(11.9%) patients were with both iron deficiency anemia and minor ß-thalassemia. There were 31(9%) patients with α-thalassemia trait and 5 (2.2%) patients with Hb H disease. Fifty six (16.2%) patients had minor ß-thalassemia. Also, there were 10 (2.9%) individuals homozygous for hemoglobin D-Punjab and one patient with hemoglobin G (0.3%). There was one sample with hemoglobin C. Further, we found 3 patients (0.9%) with sickle cell trait and more 3 patients (0.8%) with S/ ß +-thalassemia. Our results indicated that the most frequent cause of hypochromic and/or microcytic anemia in our population was IDA and the minor ß-thalassemia was the second cause that needs to more attention in screening programs.

Clinical features and types of von Willebrand disease in women with menorrhagia referred to hematology clinic of kermanshah.

Menorrhagia is the most common symptom that is experienced by women with bleeding disorders. Von Willebrand disease (VWD) is the most common congenital human bleeding disorder that is manifested as a quantitative deficiency in Von Willebrand factor (VWF) or dysfunction of this factor. The frequency of VWD is similar in both men and women. However, VWD is more readily detected in women due to the presence of severe bleeding associated with menstrual cycles and childbirth. The present study was carried out to find the frequency of VWD, its types, and clinical features of the disease among women with menorrhagia who referred to the Hematology Clinic of the Kermanshah University of Medical Sciences. The study comprised 482 women with menorrhagia. After excluding patients with confounding factors, 56 (11.6%) patients were evaluated for inherited bleeding disorders. We detected 31 (55.3%) patients with VWD. Type 3 of VWD was the most frequent subtype (45.2%) followed in frequency by type 2 (32.3%), and type 1 (22.5%). In conclusion, our study indicated that menorrhagia can be the first symptom of VWD. Therefore, rare coagulation disorders should be considered in women with idiopathic menorrhagia, particularly in regions with high rates of consanguinity.

Descriptions of acute transfusion reactions in the teaching hospitals of kermanshah university of medical sciences, iran.

BACKGROUND: Transfusion services rely on transfusion reaction reporting to provide patient care and protect the blood supply. Unnecessary discontinuation of blood is a major wastage of scarce blood, as well as man, hours and funds. The aim of the present study was to describe the main characteristics of acute transfusion reactions reported in the 4 hospital of Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran. MATERIAL AND METHODS: The study was carried out at 4 teaching hospital of Kermanshah University of Medical Sciences, Kermanshah, Iran, over18 months from April 2010. All adult patients on admission in the hospitals who required blood transfusion and had establish diagnosis and consented were included in the study. RESULTS: In the year 2010 until 2012, a total of 6238 units of blood components were transfused. A total of 59 (0.94%) cases of transfusion reaction were reported within this 3 years period. The commonest were allergic reactions which presented with various skin manifestations such as urticarial, rashes and pruritus (49.2%), followed by increase in body temperature of > 1°C from baseline which was reported as febrile non-hemolytic transfusion reaction (37.2%). pain at the transfusion site (6.8%) and hypotension (6.8%). CONCLUSION: It is important that each transfusion of blood components to be monitor carefully. Many transfusion reactions are not recognized, because signs and symptoms mimic other clinical conditions. Any unexpected symptoms in a transfusion recipient should at least be considered as a possible transfusion reaction and be evaluated. Prompt recognition and treatment of acute transfusion reaction are crucial and would help in decreasing transfusion related morbidity and mortality, but prevention is preferable.

Poor platelet Count Response to Helicobacter Pylori Eradication in Patients with Severe Idiopathic Thrombocytopenic Purpura.

INTRODUCTION: ITP is an autoimmune blood disorder in which platelet destruction is mediated by anti-platelet antibodies. The mechanisms of anti-platelet antibodies development are still a little known. The rate of some bacterial or viral agents in cause of ITP is well known. Recently, some study proposed that H pylori infection may be associated with ITP and H pylori eradication can improves platelet counts in infected ITP patients. MATERIALS AND METHOD: A baseline platelet count <50×10(3) µL for 4 weeks prior to study entry were required. These patients were tested for H. pylori infection by urea breath. All positive H pylori patients received triple therapy for 7 or 14 days to eradicate H pylori infection. These patients followed for six months. RESULTS: Of 92 patients with ITP, H pylori infection was found in 59.7% (55/92). After excluding patients with confounding factors, 41 patients were remained. After H pylori eradication, CR wasn't obtained in any patients. Partial response were obtained only in 3 (7.3%) of the 41 patients and no response in 38 (92.6%) patients. There is a significant difference between the platelet counts of PR and NR groups (P < 0.001). CONCLUSION: The results of this study and our previously study showed H pylori eradication therapy has beneficial effect for patients with mild thrombocytopenia but the chance of obtaining a response by H pylori treatment is lower in patients with severe thrombocytopenia.

Kaposi's Sarcoma after Kidney Transplantation: a 21-Years Experience.

INTRODUCTION: The long-term use of immunosuppressive agents for prevention of allograft rejection increases the risk of malignancy approximately 100 times as high as that in the general population and Kaposi's sarcoma (KS) is a relatively common malignancy after kidney transplantation. The aim of present study was to investigate the frequency of KS in patients with kidney transplantation in 20 years period. MATERIAL AND METHODS: In this study Charts and pathology reports of 1487 recipients for kidney allografts treated at Imam Reza hospital between 1991 and 2012 were reviewed. The SPSS software package version 16 (SPSS Inc., Chicago, Illinois, USA) was used for the statistical analysis. RESULTS: There were 17 of 1487 incident cases of KS kidney transplant population at our hospital in period of study. There is no significant difference between age and gender of patients. The mean time between transplantation and non-KS malignant tumors was 34.4 ± 21.8 months (range 12-140 months), while in KS patients it was 18.7 ± 25.2 months, which was statistically significantly different (P < 0.05). After detection of KS in 12 patients, we perform serum antibody detection against HHV. Among them, 8 (66.6%) were seropositive. CONCLUSION: KS is a common long-term complication in renal transplant recipients, with an increased incidence compared with the general population. Given that candidates for organ transplantation who are seropositive for HHV-8 -and thus at risk for KS- can now be identified, chemoprevention should be available in this high-risk population.

Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients.A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×10(3)/µL. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months.Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ≥50×10(3)/µL and all non-responders had platelet count <50×10(3)/µL.Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection.