Hemostatic parameters in pulmonary tuberculosis patients after intensive phase treatment.

BACKGROUND: Tuberculosis (TB) is an infectious disease caused by mycobacterium tuberculosis (Mtb). This infection causes the release of proinflammatory cytokines that affect hemostasis. Pulmonary TB infection causes an increased activation of procoagulant factors, decreased anticoagulant factors and suppresses fibrinolysis which causes hypercoagulable. Our study is conducted to assess the association between pulmonary TB infection (PTB) with hemostatic parameters before and after intensive phase treatment. METHODS: This was an analytic observational prospective cohort design. The study was conducted at the Community Center for Lung Health in South Sulawesi. Studied subjects were recruited by consecutive sampling, in which the patients who met the inclusion criteria received intensive phase of ATD treatment. PT, aPTT, fibrinogen, and D-dimer were measured before treatment and after the intensive phase of ATD. These data were analyzed using the SPSS Version 22. RESULTS: In this study, 30 subjects are new cases of PTB. Prothrombin time, aPTT and D-dimer levels were higher in far advanced lesions and smear-positive sputum group (p<0.001). There was a significant level decrease in PT, aPTT, fibrinogen, D-dimer after intensive phase treatment (p<0.001). CONCLUSION: Pulmonary tuberculosis infection is associated with hypercoagulability which is characterized by an increase in hemostatic parameters and has significant improvement after intensive phase of ATD treatment.

Profiles of endoglin and vascular endothelial growth factor based on staging and histological grading of colorectal cancer and their relationship with bevacizumab therapy / Perfis da endoglina e do fator de crescimento endotelial vascular com base no estadiamento e na graduação histológica do câncer colorretal e sua relação coma terapia com bevacizumabe

Objective: The present study evaluated the profile of endoglin (CD105) and vascular endothelial growth factor (VEGF) based on staging and histopathological grading of colorectal cancer as well as their relationship with bevacizumab therapy. Methods: A total of 88 cases of colorectal adenocarcinoma were included in the present study. The levels of VEGF and CD105 protein were evaluated with enzymelinked immunosorbent assay (ELISA). Results: There was a significant difference in the level of CD105 (p=0.002) between metastases and non-metastases subjects, showing that CD105 was higher in metastases subjects (4.59 ng/ml). Therewas no significant difference in the level of VEGF based on the presence of metastasis (p=0.625). There was a significant difference in the levels of CD105 (p=0.038) and VEGF (p=0.010) between the subjects who received chemotherapy and those who did not. The CD105 level was higher in the subjects who received chemotherapy (4.43 ng/ml); conversely, the level of VEGF was lower in subjects who received chemotherapy (543.65 pg/ml). There was a statistically significant difference in the levels of CD105 (p=0.003) and VEGF (p=0.002) between subjects who received bevacizumab therapy and subjects who did not. The levels of CD105 were higher in subjects who received bevacizumab therapy (5.11 ng/ml); in contrast, the level of VEGF was higher in subjects who did not receive bevacizumab therapy (645.92 pg/ml). There was a significant positive correlation between CD105 and VEGF in subjects who did not receive bevacizumab (p<0.01). Conclusion: The results of this study support a hypothesis of "escape mechanism" in the failure of anti-angiogenesis therapy (anti-VEGF). (AU)

Objetivo: Este estudo avaliou o perfil da endoglina (CD105) e do fator de crescimento endotelial vascular (FCEV) com base no estadiamento e graduação histopatológica do câncer colorretal, assim como sua relação com a terapia com bevacizumabe. Métodos: No total, 88 casos de adenocarcinoma colorretal foram incluídos no presente estudo. Os níveis das proteínas FCEV e CD105 foram avaliados com ensaio imunoenzimático (ELISA, na sigla em inglês). Resultados Houve uma diferença significativa no nível de CD105 (p=0,002) entre indivíduos commetástases e semmetástases, que indicou que o nível de CD105 émais alto em indivíduos com metástases (4,59 ng/ml). Não houve diferença significativa no nível de FCEV com base na presença de metástases (p=0,625). Houve diferença significativa nos níveis de CD105 (p=0,038) e de FCEV (p=0,010) entre os indivíduos que receberam quimioterapia e os que não receberam. Encontrou-se um nível de CD105 mais alto nos indivíduos que submetidos a quimioterapia (4,43 ng/ml); Em contrapartida, encontrou-se um nível de FCEV mais baixo em indivíduos que submetidos a quimioterapia (543,65 pg/ml). Houve uma diferença estatisticamente significativa nos níveis de CD105 (p=0,003) e de FCEV (p=0,002) entre os indivíduos submetidos e não submetidos à terapia com bevacizumabe. Os níveis de CD105 foram mais elevados em indivíduos submetidos à terapia combevacizumab (5,11 ng/ml); em contraste, observou-se um nível de FCEV mais alto em indivíduos que não foram submetidos à terapia com bevacizumabe (645,92 pg/ml). Houve uma correlação positiva significativa entre CD105 e FCEV em indivíduos que não receberam bevacizumabe (p<0.01). Conclusão: Os resultados deste estudo corroboram a hipótese de "mecanismo de escape" na falha da terapia anti-angiogênica (anti-FCEV). (AU)

Syndrome of Inappropriate Antidiuretic Hormone in Esophageal Cancer Patient.

Syndrome of inappropriate antidiuretic hormone (SIADH) is a disorder of fluid and sodium balance characterized by hypotonic hyponatremia, low plasma osmolality, and increased urine osmolality caused by excessive release of antidiuretic hormone (ADH). Malignancy is one of the most common causes of SIADH, but SIADH in esophageal carcinoma is very rarely reported. In this case report, a 74-year-old male patient of moderate differentiation of squamous cell esophageal carcinoma had a recurrent electrolyte balance disorder despite repeated corrections. The patient experienced improvement after fluid restriction and drug administration.

The Hypoxic Response Expression as a Survival Biomarkers in Treatment-Naive Advanced Breast Cancer.

OBJECTIVE: Hypoxia-associated biomarkers profiling may provide information for prognosis, staging, and subsequent therapy. We aim to evaluate whether the quantitative gene and protein expression of hypoxic response tumor markers - carbonic anhydrase IX (CAIX) and hypoxia- inducible factor 1 alpha (HIF1A) - may have a role in predicting survival in advanced breast cancer of Indonesian population. METHODS: Tumor tissues and peripheral blood samples were collected from treatment - naïve locally advanced (LABC) or metastatic breast cancer patients (MBC) at Wahidin Sudirohusodo General Hospital (Makassar, South Sulawesi) and its referral network hospitals from July 2017 to March 2019. The level of mRNA (of blood and tumor tissue samples) and soluble protein (of blood samples) of CAIX and HIF1A were measured by RT-qPCR and ELISA methods, respectively, besides the standard histopathological grading and molecular subtype assessment. The CAIX and HIF1A expression, patients' age, tumor characteristics, surgery status, and neoadjuvant chemotherapy drug classes were further involved in survival analyses for overall survival (OS) and progression-free survival (PFS). RESULTS: Forty (30 LABC, 10 MBC) eligible patients examined were 21 hormone-receptors positives (15 Luminal A, 6 Luminal B) and 19 hormone-receptors negatives (10 HER2-enriched, 9 triple-negative). The CAIX blood mRNA and CAIX soluble protein levels in hormone-receptors negative patients were higher than in hormone-receptor-positive patients (p < 0.05). In univariate analysis, both CAIX and HIF1A levels predict OS (except HIF1A protein) with CAIX tissue mRNA has the highest hazard ratio (HR 8.04, 95%CI:2.45-26.39), but not PFS. Cox proportional hazard model confirmed that CAIX tissue mRNA is the independent predictor of OS (HR 6.10, 95%CI: 1.16-32.13) along with surgical status and tumor advancement type (LABC or MBC). CONCLUSIONS: CAIX mRNA expression of tumor tissue in treatment-naïve advanced breast cancer has a predictive value for OS.
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Metformin improves FOXP3 mRNA expression through suppression of interferon gamma levels in pristane-induced murine models of lupus.

Background:  A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 mcl, oral metformin 100mg/kgBW, or intraperitoneal metformin 100mg/kgBW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and esosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.004). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03)  and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus. Intraperitoneal metformin, i.e intravenous administration in human, could provide a novel route of administration to improve the effect of metformin for lupus patients.

Association Between PAI-1 Activity Levels and t-PA Antigen with Glycemic Status in Prediabetic Population.

AIM: to evaluate an association between fibrinolysis defect and glycemic status in prediabetic population by assessing the levels of t-PA antigen and PAI-1 activity. METHODS: it was an observational study with cross-sectional approach. There were 72 subjects aged 30-50 years who had met the inclusion criteria. The diagnosis of diabetes mellitus (DM) and glycemic index were determined based on the American Diabetes Association (ADA) criteria. The PAI-1 and t-PA antigen levels were measured quantitatively using enzyme-linked immunosorbent assay (ELISA). Analysis between the levels of t-PA antigen and PAI-1 activity was performed using ANOVA. RESULTS: the t-PA antigen level was significantly higher in subjects with impaired glucose tolerance (IGT) and impaired fasting blood glucose (IFBG) as well as subject with impaired fasting blood glucose (IFBG) than those with normal glucose tolerance (NGT) (p=0.047). The PAI-1 activity was significantly higher in subjects with IGT, IFBG and subjects with IFBG than NGT (p=0.024). There was a significant association between glycemic status in prediabetic subjects and PAI-1 activity (p=0.04). CONCLUSION: the level of t-PA antigen and PAI-1 activity were significantly higher in prediabetic subjects than those with NGT; and there was a significant association between glycemic status in prediabetic subjects and PAI-1 activity.