The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

OBJECTIVE: Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%. MATERIAL AND METHODS: A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention. RESULTS: The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy. CONCLUSION: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey.

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.

Efficacy and Safety of Ibrutinib for Chronic Graft-Versus-Host Disease: A Systematic Review.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management. METHOD: We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies. RESULTS: A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue. CONCLUSION: The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.

The expression of hypoxia inducible factor-1 alpha in diffuse large B-cell lymphoma (DLBCL) patients: a cross-sectional study in Indonesia.

Introduction: Hypoxia fuels cancer growth by supporting blood vessel formation, suppressing immune response, and helping cancer cells adapt to harsh surroundings. This happens when cancer cells react to low oxygen levels by activating hypoxia inducible factor-1 alpha (HIF-1α). High levels of HIF-1α can indicate an aggressive form of cancer and resistance to treatment in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to identify which factors are linked to HIF-1α distribution using immunohistochemistry in DLBCL patients. Method: This study conducted at a hospital in Indonesia between 2020 and 2022 aimed to investigate factors associated with HIF-1α expression in DLBCL patients. Newly diagnosed DLBCL patients were categorized into two groups based on HIF-1α distribution (<40% and ≥40%). Various factors were analyzed between the two groups using statistical tests such as χ2, Mann-Whitney U, and Spearman correlation tests. Results: In this study, 40 participants diagnosed with DLBCL were divided into two groups based on their HIF-1α distribution. The group with HIF-1α distribution greater than or equal to 40% had a higher incidence of extranodal involvement, including primary extranodal disease, compared to the group with less than 40% distribution. This difference was statistically significant. The authors also found that haemoglobin level statistically significant (P=0.041) in this research. The Spearman test analysis showed negative correlation between haemoglobin (P = <0.05, r = -0.44) and positive correlation of soluble interleukin-2 receptor (sIL-2R) (P = <0.05, r = 0.5) with vascular endothelial growth factor (VEGF), as well as between tumour volume (P = <0.05, r = 0.37) with sIL-2R. Additionally, there was a positive correlation between VEGF and sIL-2R (P = <0.05, r= 0.5). Conclusion: Patients with higher HIF-1α expression (≥40%) had more extranodal involvement and primary extranodal disease in this study of 40 DLBCL patients. Haemoglobin level, sIL-2R, and VEGF were also identified as potential biomarkers.

Impact of independent multidisciplinary work on the survival rate of stage 3 and 4 nasopharyngeal cancer in Indonesia: a retrospective cohort study.

Background: The utilization of a multidisciplinary team (MDT) strategy is a beneficial approach in integrating the knowledge and proficiencies of various fields to produce thorough and advantageous cancer treatment plans for patients. Nevertheless, MDT has yet to be widely adopted in Indonesia. In this study, the authors examined an early form of MDT in Indonesia that does not involve dedicated meetings, referred as independent multidisciplinary work (IMW). The objective is to investigate the differences in survival rates of nasopharyngeal cancer (NPC) patients who underwent treatment with and without IMW. Materials and methods: This study has a retrospective cohort design. Data were collected from the medical records of newly diagnosed stage 3 and 4 NPC patients between 2016 and 2018. The subjects were divided into two groups: the IMW group and the non-IMW group. The primary end point of the study is overall survival rate between the two groups. Kaplan-Meier survival analysis, log-rank test, and cox proportional hazard analysis were used for statistical analysis. Results: This study included a total of 124 patients with NPC, 81 patients in the IMW group and 43 patients in the non-IMW group. At the end of the 36-month follow-up period, the median survival of the IMW group was not reached, while in the non-IMW, it was 12 months [95% confidence intervals (95% CI), 8.78-15.22], hazard ratio (HR): 0.47 (95% CI, 0.28-0.78; P<0.01). The 1-year survival rate was 66.7% in the IMW group versus 46.5% in the non-IMW group (HR=0.7, 95% CI 0.49-0.99; P=0.03); the 2-year survival rate was 40.7% in the IMW group versus 16.3% in the non-IMW group (HR=0.4, 95% CI 0.19-0.83; P<0.01). Daniel Rizky, Vina Yunarvika, and Yasjudan Rastrama Putra, these authors contributed equally to this work. In the multivariate analysis, the IMW approach, ECOG (The Eastern Cooperative Oncology Group) status, distant metastasis, and treatment approach were significantly associated with survival outcome. Conclusion: The use of IMW approach in the treatment of NPC was associated with a better survival outcome compared to non-IMW treatment.

The effect of multidisciplinary team on survival rates of women with breast cancer: a systematic review and meta-analysis.

Breast cancer is quite frequent all around the world. This disease was responsible for an estimated 2.1 million malignancies in 2022, making it the seventh-highest cause of cancer deaths globally. A multidisciplinary team (MDT) care policy was developed in the United Kingdom (UK) in 1995 to enhance the quality of care for cancer patients. The purpose of this systematic review and meta-analysis study is to assess the effects of MDT on breast cancer survival rates. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Systematic search was conducted in several international databases including Google Scholar, PubMed, EBSCOhost, and Proquest from 2012 to 2022. The authors used RevMan 5.4 to do the meta-analysis of the pooled hazard ratio. Newcastle-Ottawa Scale to measure the risk of bias. Newcastle-Ottawa Scale evaluated participant selection, comparability, and reporting of results using eight subscale items. Egger's test funnel plot was used to assess the potential publication bias for this study. Results: A total of 1187 studies were identified from research database. The authors found a total of six studies from six different countries (China, the UK, Taiwan, Australia, Africa, and France) included for this study. Based on the meta-analysis of the pooled hazard ratio of the included studies, the authors found that the overall effect size of the study was 0.80 (CI 95%: 0.73-0.88). Conclusions: Breast cancer patients who participated in well-organized MDT discussions had a greater survival rate than those who did not.

The effectiveness of atorvastatin for the prevention of deep vein thrombosis in cancer patients undergoing chemotherapy : A randomised controlled trial: open label.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication in cancer. Although thromboprophylaxis in cancer patients is recommended by the guidelines, clinicians' use of thromboprophylaxis remains limited due to cost, bleeding complications, and reluctance to give injectable anticoagulants. Inflammation plays essential roles in the pathogenesis of cancer-associated thrombosis. Owing to its ability to decrease proinflammatory cytokines, statins have anti-inflammatory properties. Thus, statins can be possibly utilized as thromboprophylaxis therapy in cancer patients undergoing chemotherapy. OBJECTIVE: To compare the effectiveness of atorvastatin and rivaroxaban for DVT prevention in high-risk thrombosis patients with cancer undergoing chemotherapy. METHODS: Double-blind, randomized controlled trial involving cancer patients with high-risk of thrombosis undergoing chemotherapy. We randomly assigned patients without deep-vein thrombosis at screening to receive atorvastatin 20 mg or rivaroxaban 10 mg daily for up to 90 days. Doppler ultrasonography was performed 90 days following chemotherapy to diagnose DVT. Average cost-effectiveness analysis was performed to analyze the cost of atorvastatin compared to rivaroxaban. RESULTS: Of the eighty six patients who underwent randomization, primary efficacy end point was observed in 1 of 42 patients (2.3%) in the atorvastatin group and in 1 of 44 (2.2%) in the rivaroxaban group (Odds Ratio [OR], 0.953; 95% confidence interval [CI], 0.240 to 3.971; p = 1.000). There was a significant difference in the incidence of major bleeding, 2 of 42 patients (4.8%) in the atorvastatin group and 12 of 44 (27.3%) in the rivaroxaban group (OR, 0.257; 95% CI, 0.07 to 0.94; p = 0.007). The average cost-effectiveness ratio of using atorvastatin was lower than that of rivaroxaban. CONCLUSION: Atorvastatin did not differ significantly from rivaroxaban in reducing the incidence of DVT, lower bleeding risk, and cost-effectiveness for thromboprophylaxis in high-risk thrombosis patients with cancer undergoing chemotherapy. The presence of limited statistical power and wide confidence intervals in this study needs further study to strengthen the efficacy of atorvastatin as DVT prophylaxis in cancer patients. TRIAL REGISTRATION: ISRCTN71891829, Registration Date: 17/12/2020.

Preliminary study of hypoxia markers in diffuse large B-cell lymphoma.

While the association of hypoxia has been established in various types of solid cancers, little is known about its presence and existence in diffuse large B-cell lymphoma (DLBCL). The purpose of the present study was to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in DLBCL and to analyze the association of these factors with several clinical and pathological characteristics. The immunohistochemical protein expression of HIF-1α and VEGF-A was investigated in 34 de novo DLBCL tumor samples from January 2017 to December 2017 from the Department of Hematology/Medical Oncology and Anatomical Pathology at Dr Kariadi Hospital (Semarang, Indonesia). The present study revealed by using immunohistochemistry (IHC), that hypoxic markers were overexpressed (88.2% for both HIF-1α and VEGF-A) in the vast majority of patients with DLBCL. Only in 4 tumors, was HIF-1α expression normal, and interestingly VEGF-A was negative as well. There was a significant correlation in the intensity of staining of HIF-1α and VEGF-A using our custom scoring system in surgically resected tissues (r=0.475; P=0.005). Both HIF-1α and VEGF-A were also associated to serum LDH and tumor diameter. Collectively, HIF-1α and VEGF-A were predominantly expressed in the majority of DLBCL tumor cells. The findings of the present study indicate the existence of hypoxia in DLBCL tumors similar to numerous solid cancers, and thus warrants further investigation to clarify its role as a potential pathogenic or prognostic marker in this type of hematological cancer.

Curcumin as adjuvant therapy to improve remission in myeloma patients: A pilot randomized clinical trial.

Background: The treatment for ineligible transplant multiple myeloma is melphalan prednisone. Curcumin has an anti-inflammatory and antiangiogenesis in cancer-directed to nuclear factor-kappa B (NF-kB) pathway. Interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and lactate dehydrogenase (LDH) were also involved in the pathogenesis of myeloma. No clinical study has evaluated the efficacy of curcumin in myeloma patients. To evaluate the efficacy of curcumin as adjuvant into melphalan prednisone in myeloma patients. Methods: 33 myeloma patients at Dr. Kariadi General Hospital, Semarang, Indonesia during 2016-2017 were randomly assigned single-blindedly into MPC (n=17) and control group (n=16). The MPC group was treated with melphalan 4 mg/m2, prednisone 40 mg/m2 for 7 days, and curcumin 8 gram daily for 28 days. The MP control group was treated with melphalan, prednisone, and placebo. The primary endpoint was the overall remission. Pre- and post-treatment was examined for NF-κB, VEGF, TNF-α, IL-6, LDH, and CRP levels All data analyses were per protocol. Results: There was a significant difference in overall remission between the MPC and MP control groups [75%vs 33.3%, x2=6.89, P=0.009]. A significant decrease of NF-κB, VEGF, TNF-α levels were shown in the MPC group compared with the MP control group. There was a significant decrease in IL-6 levels in a subgroup analysis of the MPC group. TNF-α levels had a significant correlation with remission [OR=1.35; (95%CI=1.03-1.76); P=0.03]. Conclusion: Curcumin has an efficacy in improving overall remission and decreasing NF-κB, VEGF, TNF-α, and IL-6 levels in myeloma patients.

Correlation of Inflammation and Coagulation Markers with the Incidence of Deep Vein Thrombosis in Cancer Patients with High Risk of Thrombosis.

Background: Deep vein thrombosis (DVT) is a common complication and the second leading cause of death in cancer patients. Pro-inflammatory stimuli in the cancer microenvironment induce nuclear factor kappa B (NF-κB) signaling pathway that plays an integral role in immunothrombosis mechanism. Objective: To investigate the role of inflammatory and coagulation biomarkers in the development of DVT in cancer patients with high risk of thrombosis (Khorana score ≥2). Subjects and methods: This study was a cross-sectional study at Dr. Kariadi General Hospital. The serum levels of proinflammatory cytokines, ie, NF-κB, interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and coagulation biomarkers, ie, tissue factor (TF), prothrombin fragment F1+2 (F1+2), fibrinogen and D-dimer were measured in newlydiagnosed cancer patients with a highrisk of thrombosis. Color duplex sonography was used for DVT screening. Results: From January to November 2021, there were 83 eligible patients. DVT was confirmed in 8 subjects (9.63%). Univariate analysis revealed a significant difference between the median age of patients with DVT compared to non-DVT patients, 49.5 years (range: 23-60 years) and 42 years (range: 19-60 years), with p=0.046. D-dimer level was higher in DVT patients [(6.020 µg/L, range 2.090-20.000) vs (1.940 µg/L, range 270-20.000), p=0.005]. Multivariate analysis revealed age and D-dimer were significantly correlated with DVT incidence. In all patients, there were significant positive correlations between several inflammatory and coagulation activation parameters, which were IL-6 with D-dimer and F1+2, CRP with F1+2 and D-dimer as well as TNF-α with F1+2. However, these findings were not shown in DVT patients. Conclusion: In cancer patients with a high risk of thrombosis, age and D-dimer level are the significant variables towards the incidence of DVT. In patients with DVT, there was no significant correlation between inflammatory and coagulation activation parameters.

Preventing Thrombosis in Cancer Patients.

Thromboembolism events, either venous (VTE) or arterial thromboembolism (ATE) remain a highly prevalent complication in cancer patients. Thrombosis is a leading cause of death, contributor to significant morbidity, the reason of delayed cancer treatment, leading to increased cancer financing and expenses. Both cancer and its treatment are recently found to be related to vascular inflammation through the induction of tissue factor (TF) expression and promoting a procoagulant state which triggers the activation of coagulation system. Several risk factors may also coexist such as dehydration, immobilization, smoking, obesity, previous DVT, etc. Even in patients with asymptomatic deep vein thrombosis (DVT), they have a three-fold increase in mortality. The high morbidity and mortality of VTE raises the need for thromboprophylaxis to reduce the incidence of overt thrombosis, albeit against its possible side effects related to anticoagulant prescription. This article highlighted the clinical perspectives for thromboprophylaxis while counting on the risk stratification in a particular cancer patient.

A full-term pregnant woman with secondary Evans syndrome caused by severe coronavirus disease 2019: a case report.

BACKGROUND: In this report, we describe a very challenging case of a patient with secondary Evans syndrome caused by severe coronavirus disease 2019 infection in a pregnant full-term woman. CASE PRESENTATION: A 29-year-old full-term pregnant Indonesian woman presented with gross hematuria, dry cough, fever, dyspnea, nausea, anosmia, and fatigue 5 days after confirmation of coronavirus disease 2019 infection. Laboratory examinations showed very severe thrombocytopenia, increased indirect bilirubin, and a positive direct Coombs' test. From peripheral blood, there was an increased number of spherocytes, which indicated an autoimmune hemolytic process. Antinuclear antibody and anti-double-stranded DNA test results were negative, and her virology serological markers are also negative for human immunodeficiency virus, cytomegalovirus, and hepatitis B and C. Despite aggressive treatment with platelet transfusion, high-dose steroid, and thrombopoietin receptor agonists, the platelet count did not recover, and a speculative cesarean delivery had to be done with a very low platelet count.

The Use of Etoposide, Ara-Cytarabine, and Melphalan (EAM) Conditioning Chemotherapy in Autologous Stem Cell Transplantation (ASCT) for a Patient with Relapsed Hodgkin's Lymphoma.

Up to 20-40% of patients with Hodgkin's lymphoma will eventually relapse after treatment, among which early relapse confers a poor outcome. With salvage chemotherapy followed by autologous stem cell transplantation (ASCT), the long-term remission rate is 30%. We report our experience of using a modified-BEAM conditioning regimen without BCNU consisting of etoposide, cytarabine, and melphalan (EAM) in a patient with relapsed Hodgkin's lymphoma. Before transplantation, the patient achieved second complete remission (CR2) using brentuximab vedotin and ESHAP (BR-ESHAP) chemotherapy. The ASCT went well without significant complications. This case demonstrated the considerable efficacy of EAM protocol as a conditioning regimen in terms of sufficient ablative capabilities, and the patient showed a successful hematopoietic engraftment. Although durability of the disease-free survival needs further observation, it had nearly 18 months of complete remission and the patient was in good performance status at the time of writing this manuscript.

Von Willebrand factor:antigen and ADAMTS-13 level, but not soluble P-selectin, are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy.

BACKGROUND: There is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy. METHODS: This prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy. RESULTS: DVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15-12.48, p = 0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22-23.82, p = 0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance. CONCLUSION: We found that prechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence among cancer patients.

Clinical Evaluation for the Role of High-Sensitivity C-Reactive Protein in Combination with D-Dimer and Wells Score Probability Test to Predict the Incidence of Deep Vein Thrombosis Among Cancer Patients.

BACKGROUND: Deep vein thrombosis (DVT) is a frequent complication in cancer patients and is the second leading cause of death. The high level of C-reactive protein (CRP) is an acute phase reactant that induces tissue factor (TF) expression in monocytes, smooth muscle cells, and endothelial cells. The CRP level positively correlates with the incidence, extension, and volume of thrombus. TF expression triggers the coagulation system including the formation of thrombin and circulating fibrin such as prothrombin fragment 1+2 (F1 + 2) and D-dimer. OBJECTIVE: To determine the diagnostic value of high-sensitivity (hs)-CRP, D-dimer, and Wells score combination to predict the incidence of DVT on clinically suspected DVT (Wells score ≥2) cancer patients. SUBJECTS AND METHODS: This study was a cross-sectional study on a diagnostic test to determine the diagnostic value of hs-CRP and D-dimer for early detection of DVT on clinically suspected DVT (Wells score ≥2) cancer patients. It was conducted in Dr. Kariadi Hospital, Semarang Indonesia on 35 subjects. The diagnosis of DVT was confirmed by color duplex sonography. The diagnostic accuracy of combination of hs-CRP, D-dimer, and Wells score was analyzed by logistic regression. RESULTS: DVT was confirmed in 10 subjects (28,6%). The cut-off point of hs-CRP levels for probable DVT was ≥51.05 mg/L and for D-dimer was ≥5030 µg/L. The median levels of both variables were higher in the subjects with DVT compared with the subjects without DVT, but it was not statistically significant. The combination of hs-CRP (≥51.05 mg/L), D-dimer (≥5030 µg/L), and Wells score ≥3 had the high accuracy (94.1%) to predict the incidence of DVT compared with hs-CRP (65.0%), D-dimer (54.7%), and combination of hs-CRP and D-dimer (71.0%). CONCLUSION: The combination of hs-CRP (≥51.05 mg/L), D-dimer (≥5030 µg/L), and Wells score ≥3 can predict the incidence of DVT in cancer.

High sensitivity C-reactive protein as a predictive of intima-media thickness in patients with end-stage renal disease on regular hemodialysis.

BACKGROUND: Several emerging problems of regular hemodialysis (HD) including cardiovascular complication or atherosclerosis formation caused by chronic inflammation. Intima-media thickness (IMT) of the carotid artery can be applied as a marker of atherosclerosis progression. This study was designed to identify the predictive of IMT progression among end-stage renal disease (ESRD) subject. METHODS: This cohort study was performed at the Hemodialysis Unit of Dr. Kariadi Hospital and Telogorejo Hospital Semarang between October 2009 and April 2010. The study subjects were the ESRD patients with regular HD. RESULTS: This study enrolled 78 subjects with regular HD, follow-up 6 months. The subjects which completed the study were divided into two groups that consist of IMT progressive group (n=53) and IMT non-progressive group (n=12). There were no differences between two groups according to age, gender, history of diabetes, blood pressure, duration of HD, urea, creatinine, blood glucose, HbA1C, cholesterol, triglyceride, HDL, uric acid, phosphate, calcium, homocysteine, and albumin. Subject with high-sensitive C-reactive protein (hsCRP) level >0.52 mg/L had an IMT progression. There was a correlation between hsCRP and the thickening of carotid artery wall after 6-month HD (RR=3.6; 95% CI=2.2-22.9). The subject with hsCRP level >9.00 mg/L after 6-month dialysis progress to thickening of carotid artery wall of >0.03 mm. There was a correlation between hsCRP level (cut-off point: 9.0 m/L) and the progression of the carotid artery wall (RR=2.1; 95% CI=1.3-3.37). Statistically, there was no correlation between IL-6-174 G/C gene and eNOS gene polymorphism with IMT progression. CONCLUSION: hsCRP is a significant predictive of IMT progression at hemodialysis subject. IL -174 G/C gene and eNOS gene polymorphism are not significant predictive of IMT progression at hemodialysis subject.