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BACKGROUND: STAT5 is a transcriptional factor which when highly expressed in chronic myeloid leukemia (CML) cells stimulate proliferation and mediate resistance from tyrosine kinase inhibitors, resulting in major molecular response (MMR) failure. STAT5 has two isoforms, STAT5A and STAT5B. However, prolonged use of imatinib appears to only upregulate STAT5A pathway. In addition, the resistance conferred by STAT5A does not extend to other drugs such as hydroxyurea. Hence, STAT5A and STAT5B might have different functions in CML cells. AIM: The objective of the study was to determine the association of STAT5A and STAT5B expression with MMR failure in CML patients. METHODS: This was a cross-sectional study of CML patients in chronic phase with age ≥ 18 years old, receiving IM therapy ≥ 12 months, and previously given hydroxyurea. MMR status was evaluated and patients were categorized as achieved or failed to achieve MMR. Expression levels of STAT5A and STAT5B were conducted using RT-PCR methods. Associations between STAT5A expression, STAT5B expression, hydroxyurea duration, and imatinib duration with MMR achievement were calculated using logistic regression. RESULTS: A total of 118 patients were analyzed; 71.1% failed to achieve MMR. Multivariate logistic regression analysis showed statistically significant association between high STAT5A expression (odds ratio [OR]: 3.852; 95% confidence interval [CI]: 1.420–10.452; p = 0.008), STAT5A/STAT5B interaction (OR: 0.150; 95% CI: 0.038–0.593; p = 0.007), longer hydroxyurea administration (OR: 3.882; 95% CI: 1.023–14.733; p = 0.046), and shorter imatinib administration (OR: 0.333; 95% CI: 0.132–0.840; p = 0.020) with MMR achievement failure. After adjusting STAT5A expression with STAT5A/STAT5B interaction, high STAT5A expression independently increased the likelihood of MMR achievement failure only in high expression STAT5B patients (OR: 3.852; 95% CI: 1.420–10.452; p = 0.008). CONCLUSION: High STAT5A expression which is induced by high STAT5B is associated with MMR achievement failure of chronic phase CML patients who received hydroxyurea before imatinib. Longer duration of hydroxyurea and shorter duration of IM confound of STAT5A expression to MMR achievement failure.

Ikhwan Rinaldi,1 Resti Mulya Sari,2 Vanya Utami Tedhy,3 Kevin Winston3 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Division of Hematology and Medical Oncology, Department of Internal Medicine, Dharmais National Cancer Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan RinaldiDivision of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, IndonesiaTel +628111001758Email ikhwan.rinaldi@ui.ac.idIntroduction: Leukostasis is a medical emergency with high mortality which often occurs in acute myeloid leukemia patients with hyperleukocytosis. One of the therapies that can be used for leukostasis in acute myeloid leukemia is leukapheresis. However, whether leukapheresis can provide better survival benefit when compared with patients not receiving leukapheresis is still unclear. Hence, we aimed to evaluate the effect of chemotherapy plus leukapheresis combination versus chemotherapy only on 28-day survival of acute myeloid leukemia patients with leukostasis.Methods: This study was a dual-center retrospective cohort using secondary data from medical records collected from November 2018 to March 2019. Inclusion criteria were adult patients aged 18 years old or above, diagnosed with acute leukemia with hyperleukocytosis status defined by WBC count greater than 100,000/uL, and with symptoms of leukostasis. One-month survival analysis was conducted using Kaplan–Meier curve method. Univariate and multivariate analyses were then conducted using Cox proportional hazards model to obtain value of hazard ratio (HR) with a 95% confidence interval (CI).Results: A total of 38 patients were obtained for analysis. The median overall survival was 25 days (95% CI: 17.001– 32.999 days) in the chemotherapy only group and 20 days (95% CI: 1.497– 38.503) in the chemotherapy with leukapheresis group. The use of leukapheresis did not affect 28-day survival (HR: 1.140; 95% CI: 0.396– 3.283; p value: 0.809) and 7-day survival (HR: 1.073; 95% CI: 0.277– 4.152; p value: 0.919). In the multivariate analysis, age ≥ 60 years, blast percentage ≥ 90%, creatinine ≥ 1.4 mg/dL, and presence of disseminated intravascular coagulation were associated with worse 28-day survival.Conclusion: AML patients with leukostasis who received both chemotherapy and leukapheresis did not have better 28-day survival and 7-day survival when compared with patients receiving chemotherapy only. Old age, high blast percentage, high creatinine, and presence of disseminated intravascular coagulation were prognostic factors for worse 28-day survival.Keywords: leukemia, hyperleukocytosis, leukostasis, leukapheresis, chemotherapy, survival

Background Readmission is related to high cost, high burden, and high risk for mortality in geriatric patients. A scoring system can be developed to predict the readmission of older inpatients to perform earlier interventions and prevent readmission. Methods We followed prospectively inpatients aged 60 years and older for 30 days, with initial comprehensive geriatric assessment (CGA) on admission in a tertiary referral centre. Patients were assessed with CGA tools consisting of FRAIL scale (fatigue, resistance, ambulation, illness, loss of weight), the 15-item Geriatric Depression Scale, Mini Nutritional Assessment short-form (MNA-SF), the Barthel index for activities of daily living (ADL), Charlson Comorbidity Index (CCI), caregiver burden based on 4-item Zarit Burden Index (ZBI), and cognitive problem with Abbreviated Mental Test (AMT). Demographic data, malignancy diagnosis, and number of drugs were also recorded. We excluded data of deceased patients and patients transferred to other hospitals. We conducted stepwise multivariate regression analysis to develop the scoring system. Results Thirty-day unplanned readmission rate was 37.6 %. Among 266 patients, 64.7 % of them were malnourished, and 46.5 % of them were readmitted. About 24 % were at risk for depression or having depressed mood, and 53.1 % of them were readmitted. In multivariate analysis, nutritional status (OR 2.152, 95 %CI 1.151–4.024), depression status (OR 1.884, 95 %CI 1.071–3.314), malignancy (OR 1.863 95 %CI 1.005–3.451), and functional status (OR 1.584, 95 %CI 0.885–2.835) were included in derivation of 7 score system. The scoring system had maximum score of 7 and incorporated malnutrition (2 points), depression (2 points), malignancy (2 points), and dependent functional status (1 point). A score of 3 or higher suggested 82 % probability of readmission within 30 days following discharge. Area under the curve (AUC) was 0.694 (p = 0.001). Conclusions Malnutrition, depression, malignancy and functional problem are predictors for 30-day readmission. A practical CGA-based 7 scoring system had moderate accuracy and strong calibration in predicting 30-day unplanned readmission for older patients.

Introduction Cancer and its treatment have a broad impact on patients' Quality of Life (QoL). Previous researches showed that many factors in Comprehensive Geriatric Assessment (CGA) affect QoL. CGA could predict toxicity, overall survival rate and can help adjust the choice and intensity of treatment in each patient. However, there has been no research explicitly exploring factors related to the QoL in older patients with Non-Hodgkin's Lymphoma (NHL). This research aims to explore the how factors in CGA relate to the QoL in older patients with NHL. Materials and Method The study design was cross-sectional in NHL patients aged ≥ 60 years, research was conducted in Integrated Geriatric Polyclinic and Hemato-Oncology Polyclinic of three public hospitals in Jakarta, during March–August 2019. Results There were 62 subjects, with a median age of 66 years, 56.5% male. The result showed that most of the patients have a good QoL, based on each domain of SF-36 and EORTC QLQ-C30. In multivariate analysis, it was found that depression and frailty status were related to PCS SF-36 domain with PR 12.086 (95% CI 1.596–92.124) and PR 5.622 (95% CI 1.060–29.807), respectively. Multivariate analysis with SF-36's Mental Component Summary (MCS) showed a significant relationship with depression status with PR 24.400 (95% CI 2.961–140.539). While the results of multivariate analysis with the EORTC QLQ-C30 functional scale showed a significant relationship with the ECOG performance score with PR 171 (95% CI 8.470–3452.28). Discussions After multivariate analysis, only frailty status, depression status and ECOG performance score have a statistically significant relationship.

Ikhwan Rinaldi,1 Melva Louisa,2 Resti Mulya Sari,3 Elly Arwanih1 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Division of Hematology and Medical Oncology, Department of Internal Medicine, Dharmais Cancer Hospital,Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan RinaldiCipto Mangunkusumo National General Hospital, Jakarta, IndonesiaEmail ikhwanrinaldi@gmail.comObjective: To analyze theassociation of FLT3-ITD mutation and FLT3 ligand plasma level with one-year survival of Indonesian acute myeloid leukemia (AML) patients.Methods: A prospective cohort study was conducted to determine the association between FLT-3-ITD mutation and FLT3 ligand plasma level with one-year survival of Indonesian AML patients. In the study, a total of 51 AML patients were obtained from two tertiary hospitals in Indonesia from year 2018 to 2020. Inclusion criteria were de novo AML male and female patients aged ≥ 18 years old. Exclusion criteria were prior myelodysplastic syndrome and patients that refused to participate in the study. FLT3-ITD genotype of patients was then analyzed using PCR method while FLT3 ligand plasma level was measured using ELISA method. Patients were then followed-up for 1 year or until death occurred with survival as the measured outcome. Association between independent and dependent variable were analyzed by cox regression proportional hazard.Results: Eleven patients (21.5%) in this study had FLT3-ITD mutation. The median age of AML patients was 45 (18– 71) years, and the median blast percentage was 50% (5– 87%). After one-year follow-up, 33 (64.7%) patients had died. The median survival of AML patients was 6 months. Univariate analysis showed no association between FLT3-ITD mutation status (HR: 1.051 ; 95% CI: 0.483– 2.286; P: 0.901) and FLT3 ligand plasma level (HR: 0.798; 95% CI: 0.347– 1.837; p= 0.596), and age (HR: 1.283; 95% CI: 0.575– 2.862; p= 0.542) with one-year survival of AML patients, but multivariate analysis showed association between GFR with one-year survival of AML patients in this cohort (HR: 4.053; 95% CI: 1.469– 11.183; p= 0.007).Conclusion: One-year survival of AML patients in Indonesia is not affected by FLT3-ITD mutation and FLT3 ligand plasma level. However, GFR showed association with one-year survival of AML patient in this cohort study.Keywords: acute myeloid leukemia, one-year survival, FLT3-ITD, FLT3 Ligand Plasma

We investigated the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) and its correlation with fibrosis and steatosis stratified by body mass index, as reflected in the controlled attenuation parameter and transient elastography values. A cross-sectional study was performed on 37 patients with NAFLD at Cipto Mangunkusumo National General Hospital from December 2018 to March 2019. The gut microbiota was investigated in fecal samples with 16S RNA sequencing using the MiSeq next-generation sequencing platform (Illumina). NAFLD was more common in patients with metabolic syndrome. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla. Bacteroides was more dominant than Prevotella, contrary to the results of previous studies on healthy populations in Indonesia. Microbiota dysbiosis was observed in most samples. The gastrointestinal microbiota diversity was significantly decreased in patients with NAFLD, high triglyceride levels, and central obesity. The Firmicutes/Bacteroidetes ratio correlated with steatosis and obesity, whereas some of the other species in lower taxonomy levels were mostly associated with steatosis and obesity without fibrosis. Proteobacteria was the only phylum strongly correlated with fibrosis in patients with an average body mass index. The gut microbiota diversity was decreased in patients with NAFLD, high triglyceride levels, and central obesity, and certain gut microbes were correlated with fibrosis and steatosis.

Cosmas Rinaldi Adithya Lesmana,1,2 Yoppi Kencana,1 Ikhwan Rinaldi,3 Juferdy Kurniawan,1 Irsan Hasan,1 Andri Sanityoso Sulaiman,1 Rino Alvani Gani1 1Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia; 2Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta, Indonesia; 3Department of Internal Medicine, Haematology and Oncology Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Cosmas Rinaldi Adithya LesmanaDepartment of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jalan Diponegoro No. 71, Jakarta, IndonesiaEmail medicaldr2001id@yahoo.comBackground: Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease with excessive fat accumulation in the liver. Transient elastography (TE) with controlled attenuation parameter (CAP) is a device and method to examine the degree of fibrosis and steatosis. However, this device is not widely available across Indonesia. Neutrophil and lymphocyte ratio (NLR) is a simple marker for inflammation, which has a potency to predict disease outcome. This study aims to know the diagnostic value of NLR as the indicator of steatosis and fibrosis severity.Methods: This was a cross-sectional study with consecutive sample collection. We used secondary data from medical records, starting from 2016 to 2018. A descriptive and data analysis, including correlation test, multivariate linear regression, t-test, receiver operating curve (ROC) and area under the curve (AUC) were done to find out the outcome of the study. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) Version 20.0 (SPSS Inc, Chicago, Illinois). A P value < 0.05 was considered as statistically significant.Results: Out of 106 subjects, 62.3% patients were women with the mean of age 57.29 years old and 77.4% had metabolic syndrome. Most patients had moderate to severe steatosis degree (66%) with the mean of TE mean 6.14 (2.8– 18.2) kPa. There was a positive correlation between CAP and TE compared with NLR with r = 0.648 (p < 0.001) and r = 0.621 (p < 0.001), respectively. The use of RNL to assess moderate-severe steatosis has a cutoff point of 1.775 with sensitivity, specificity, PPV and NPV, respectively, at 81.5%, 80.6%, 89.1%, and 69.1%; cutoff point 2.150 to assess significant fibrosis with sensitivity, specificity, PPV and NPV of 92.3%, 87.5%, 70.6%, and 97.2%, respectively.Conclusion: NLR has a positive and significant correlation with the degree of steatosis and fibrosis with high sensitivity and specificity as evaluated by TE/CAP.Keywords: neutrophil and lymphocyte ratio, steatosis, fibrosis, non-alcoholic fatty liver disease

BACKGROUND The risk of hepatitis C virus (HCV) infection is increasing in patients under routine hemodialysis, but only some patients progress to liver fibrosis. This study was aimed to identify the prevalence of significant liver fibrosis in routine hemodialysis patients with hepatitis C infection as well as factors associated with liver fibrosis. METHODS This cross-sectional study was conducted in three tertiary general hospitals (Cipto Mangunkusumo Hospital, Persahabatan Hospital, and Fatmawati Hospital) in Jakarta, Indonesia, among hemodialysis patients infected with HCV. Total sampling was used from May to September 2017 in hemodialysis unit of all hospitals. Sex, age, time at first diagnosis of HCV, duration of HCV infection, duration of hemodialysis, AST level, hepatitis B virus coinfection and diabetes mellitus were analyzed in association with significant liver fibrosis. Liver fibrosis was assessed using transient elastography and considered significant if the value was ≥7.1 kPa. Chi-square, Mann–Whitney U, and Fisher’s exact tests were used. Risk model was analyzed with logistic regression. RESULTS Of the 133 hemodialysis patients infected with HCV, 71.4% of the subjects had significant liver fibrosis. In the risk model, male gender (odds ratio [OR] = 3.92; 95% confidence interval [CI] = 1.74–8.84; p < 0.001) and diabetes mellitus (DM) (OR = 2.85; 95% CI = 1.03–7.88; p = 0.043) were associated with significant liver fibrosis. CONCLUSIONS The prevalence of significant liver fibrosis in routine hemodialysis patients with hepatitis C infection was high. Male and DM were associated with significant liver fibrosis.

Platelet to lymphocyte ratio (PLR) is a candidate prognostic marker for metastatic castration‐resistant prostate cancer patients receiving abiraterone acetate and evidence demonstrates that a high PLR is associated with poor survival. More studies are required to verify current findings and establish a definite cutoff point.

Background: Dysbiosis of the gut microbiota has been considered to have a role in nonalcoholic fatty liver disease (NAFLD) progression. However, there is still lack of studies regarding this phenomenon. Aim: To find the difference in the proportion of gut microbiota in NAFLD patients based on the stages of liver fibrosis. Patients and Methods: A cross-sectional study was conducted at Dr. Cipto Mangunkusumo Hospital, which is the largest tertiary referral center. Human fecal samples from NAFLD patients who came to the outpatient clinic were collected consecutively. The stool sample examination was performed using an isolation DNA kit (Tiangen) and quantitative real-time polymerase chain reaction (Fast 7500). Clinical and laboratory data were also collected. The stage of fibrosis was diagnosed based on transient elastography (FibroScan® 502 Touch; Echosens, France). Results: Of 60 NAFLD human fecal samples, 35 patients had nonsignificant fibrosis and 25 patients had significant fibrosis (46.7% male and 53.3% female; median age 56 years). Most patients had diabetes (85%), dyslipidemia (58.3%), obesity (58.3%), and central obesity (90%). The proportion of Bacteroides was higher when compared to Lactobacillus and Bifidobacteria. Of these 3 microbiota, the proportion of Bacteroides was significantly higher in the significant fibrosis group when compared to the nonsignificant fibrosis group. Conclusion: There is a change in the composition of gut microbiota in NAFLD patients. The proportion of Bacteroides is significantly higher in significant liver fibrosis, which may play a role in NAFLD progression.

The inflammatory process of head and neck cancer leads to an increase the proinflammatory cytokines and the synthesis of c-reactive protein (CRP), which then causes metabolic alteration and anorexia in the patients. Zinc is one of nutrient that has an important role in suppressing inflammation, but it is reported that about 65% of head and neck cancer patients have zinc deficiency. The aim of this cross sectional study is to determine the correlation between zinc intake and serum zinc levels with CRP level as an effort in reducing inflammation process in head and neck cancer patients. Subjects were collected by consecutive sampling in the Oncology Polyclinic Rumah Sakit Kanker Dharmais, from 49 subjects 67,3% were men, most subjects were in the age range between 46–65 years. The highest frequency (65,3%) is nasopharyngeal cancer and 69,4% are already in stage IV. All subjects (100%) in this study have a zinc intake below the recommended dietary allowance (RDA) in Indonesia. The mean serum zinc level of the subjects was 9.83±2.62 μmol/L. Most subjects have elevated CRP levels. There was a weak negative correlation between zinc concentration and CRP levels of subjects (r =-0.292, p =0.042), but there was no correlation between zinc intake and CRP levels of subjects (r =-0.25).

Objective: This study aimed to identify the association between duration of HU administration prior to IM treatment and MMR achievement in chronic-phase CML while evaluating the role of MDA, HIF-1α and P-gp. Methods: The study was conducted at Dr. Cipto Mangunkusumo National General Hospital and Dharmais Cancer Hospital, Jakarta using retrospective cohort design to analyse the association between the duration of HU before IM and its MMR achievement and cross-sectional design to analyse the association between MDA, HIF-1α and P-gp expressions with MMR achievement. Main subjects were chronic-phase CML patients treated by HU prior to IM for ≥ 12 months and HU only. The subjects were divided into four main groups: (1) chronic-phase CML patients treated with HU ≤ 6 months + IM ≥ 12 months and (2) HU > 6 months + IM ≥ 12 months (3) HU only (≤ 6 months), (4) HU only ( >6 months). Subjects were obtained from January 2015 to May 2016. Data were gathered through history taking, physical examination, medical record evaluation, and blood sample analysis. Bivariate analysis was conducted using chi square, independent T-test, and Mann-Whitney according to the variables. Results: Administration of HU for more than 6 months prior to IM was associated with unsuccessful MMR achievement (RR 1.60; 95%CI 1.29-2.00). MDA level, HIF-1α, P-glycoprotein expression were not associated with MMR achievement but the mean MDA level (0.63±0.31 vs 0.75±0.41 p=0.461) and median P-glycoprotein expressions {16,92 (0,04 – 43,86) vs. 5,15 (0,02–39,64); p=0.311} were found to be higher in patients receiving HU for > 6 months group than in HU ≤ 6 months group consecutively. Conclusion: Administration of HU for more than 6 months prior to IM was associated with unsuccessful MMR achievement in chronic-phase CML. The study suggested that P-glycoprotein overexpression as the predictor for unsuccessful MMR achievement.

Objective: Imatinib is the first-line drug used for the treatment of chronic myeloid leukemia (CML) patients due to high molecular response and overall survival rate. However, some patients develop resistance to imatinib even after attaining a response. Mutation in ABCB1 efflux transporters is one of the known mechanisms of resistance to imatinib in chronic myeloid leukemia patients. This study was aimed to investigate the association of ABCB1 C1236T polymorphism in Indonesian chronic myeloid patients with molecular response to imatinib treatment. Methods: We analyzed 120 samples from chronic myeloid leukemia patients in the chronic phase, who had been on imatinib treatment for at least 12 months. We analyzed the C1236T variant of the ABCB1 gene using PCR, followed by direct sequencing, and associate them with the achievement of major molecular response (MMR). Results: The major molecular response was achieved in 28% of patients. The frequencies of the SNPs were CC (40%), CT (46%), and TT (14%). Our result showed that there was a lack of association between polymorphism of ABCB1 C1236T and imatinib response in Indonesian patients, with OR = 0.646 (95% CI: 0.283, 1.471; p>0.05). Conclusion: There was no association between ABCB1 C1236T variants with the major molecular response in Indonesian chronic myeloid leukemia patients receiving imatinib treatment.

Ikhwan Rinaldi,1 Rachmat Hamonangan,2 Mohamad Syahrir Azizi,3 Rahmat Cahyanur,1 Fadila Wirawan,4 Atikah Isna Fatya,4 Ageng Budiananti,4 Kevin Winston4 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; 2Department of Internal Medicine, PGI Cikini Hospital, Jakarta, Indonesia; 3Division of Cardiology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan RinaldiDivision of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, IndonesiaTel +62 811177997Email ikhwanrinaldi@gmail.comIntroduction: Patients with deep vein thrombosis (DVT) pose high morbidity and mortality risk thus needing fast and accurate diagnosis. Wells clinical prediction scores with D-dimer testing are traditionally used to rule out patients with low probability of DVT. However, D-dimer testing has a few limitations regarding its relatively low specificity. Neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was found to increase in DVT. Hence, we aimed to evaluate the role of NLR for DVT diagnosis.Methods: Data were collected from medical records of patients with suspected DVT at Cipto Mangunkusumo National General Hospital during January–December 2014. Diagnosis of DVT was conducted using lower limb ultrasonography. Diagnostic values for NLR, D-dimer, and NLR + D-dimer were determined by receiver operating characteristic (ROC) analysis to obtain area under the curve (AUC), sensitivity, specificity, negative predictive value, and positive predictive values. Sensitivity and specificity analyses of NLR and D-dimer were also conducted based on Wells score and divided into groups of low and high probability of DVT.Results: The AUC values for NLR, D-dimer, and NLR + D-dimer were 72.6%, 70.4%, and 76.1%, respectively. The optimal cut-off value determined for NLR was 5.12 with sensitivity of 67.7%, specificity of 67.9%, PPV of 68.85%, and NPV of 64.91% in differentiating subjects with and without DVT. This study also found that D-dimer had sensitivity of 69.4%, specificity of 71.4%, PPV of 72.88%, and NPV of 67.8%. Meanwhile, the NLR + D-dimer combination had sensitivity of 66.1% and specificity of 72.6%. Multivariate analysis showed that NLR (OR: 2.636; 95% CI: 1.144– 6.076; p: 0.023) and D-dimer (OR: 4.175; 95% CI: 1.810– 9.633; p: 0.001) were associated with DVT.Conclusion: NLR value has wider AUC than D-Dimer and is relatively easier to obtain and does not require specific assay, thus enabling rapid evaluation of symptomatic patients suspected of having DVT. Adding NLR to D-dimer increased AUC to detect DVT. Therefore, NLR could serve as a complementary diagnostic tool for D-dimer to exclude DVT, especially in low clinical probability patients.Keywords: deep vein thrombosis, neutrophils lymphocyte ratio, NLR, inflammation, D-dimer

Background. Acquired hemophilia A (AHA) is a potentially life-threatening autoimmune hemostatic disorder where autoantibodies that disrupt the functions of factor VIII (FVIII) are present in the circulation. The early diagnosis of AHA is difficult since the symptoms of AHA differ from those of congenital hemophilia A. Furthermore, the management of AHA is also more complex due to the presence of autoantibodies against FVIII (FVIII inhibitors). Here, we present three case reports and conduct a literature review of AHA with the aim to increase awareness and knowledge regarding the diagnosis and treatment of AHA. Case Presentations. We present three patients diagnosed with AHA in these case reports. The first patient was a young female, while the second and third patients were middle-aged and elderly males, respectively. All patients presented with a chief complaint of bruises without hemarthrosis and a history of bleeding. Laboratory examinations of the patients revealed isolated prolonged aPTT, normal PT, and the presence of autoantibodies against factor VIII, which are characteristics of AHA. Patients were then treated with corticosteroids to reduce the titer level of autoantibodies and received factor VIII transfusion to stop bleeding. Conclusion. AHA can be suspected in patients presenting with symptoms of bruises without hemarthrosis and without the history of bleeding. Isolated aPTT elevation with normal PT should raise high suspicion of AHA. The presence of FVIII inhibitors can help to confirm the diagnosis of AHA. Treatment consists of factor VIII transfusion and corticosteroid therapy. Bypassing agents are recommended as an alternative to FVIII transfusion.

ObjectiveThis study will test the performance of the anal swab PCR test when compared with the nasopharyngeal swab PCR test as a diagnostic tool for COVID-19.DesignAn observational descriptive study which included hospitalised suspected, or probable cases of hopitalised COVID-19 patients, conducted in Dr. Cipto Mangunkusumo National Hospital, Ciputra Hospital, Mitra Keluarga Depok Hospital and Mitra Keluarga Kelapa Gading Hospital, Indonesia. Epidemiological, clinical, laboratory and radiology data were obtained. Nasopharyngeal and anal swabs specimens were collected for SARS-CoV-2 RNA detection.ResultsWe analysed 136 subjects as part of this study. The clinical spectrum of COVID-19 manifesation in this study was typical of hospitalised patients, with 25% classified as mild cases, 14.7% in severe condition and 12.5% of subjects classified as having acute respiratory distress syndrome. When compared with nasopharyngeal swab as the standard specimen for reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 antigen, the sensitivity and specificity of the anal swab was 36.7% and 93.8%, respectively. The positive and negative predictive value were 97.8% and 16.5 %, respectively. The performance of the anal swab remained similar when only the subgroup of patients with gastrointestinal symptoms (n=92, 67.6%) was analysed (sensitivity 40% and specificity 91.7%). Out of all the subjects included in analysis, 67.6% had gastrointestinal symptoms. Similarly, 73.3% of patients in the anal swab-positive group had gastrointestinal symptoms. The two most common gastrointestinal symptoms in the subjects’ population were nausea and anorexia.ConclusionAnal swab specimen has low sensitivity (36.7%) but high specificity (93.8%) for detecting SARS-CoV-2 antigen by RT-PCR. Only one additional positive result was found by anal swab among the nasopharyngeal swab-negative group. Anal swab may not be needed as an additional test at the beginning of a patient’s diagnostic investigation and nasopharyngeal swab RT-PCR remains as the standard diagnostic test for COVID-19.

Background The association between prior exposure to immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. As the current evidence remains equivocal, this meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and hospitalization.Methods Eligible studies published up to 14 September 2020 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with 95% confidence intervals (CIs). The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results Six studies involving a total of 1647 COVID-19-infected cancer patients were included in the systematic review. We discovered that prior ICI exposure was not associated with COVID-19 mortality (odds ratio [OR] 0.93 [95% CI: 0.37-2.36]; I2=30%), severity (OR 1.15 [95% CI: 0.40-3.28]; I2=0%), and hospitalization (OR 1.35 [95% CI: 0.64-2.87]; I2=51%). However, we discovered that prior exposure to chemoimmunotherapy predicted COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2=0%), albeit with small sample size. GRADE assessments resulted in moderate-quality evidence for mortality, while the other outcomes yielded very low-to-low-quality evidenceConclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased, especially in patients receiving chemoimmunotherapy. Further studies with larger ICI cohorts are required to confirm our findingsTrial registration number: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.

Background The association between immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. This meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and any other prognosis-related outcomes. Methods Eligible studies published up to 27 February 2021 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with its 95% confidence intervals. The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation framework. Results Eleven studies involving a total of 2826 COVID-19-infected cancer patients were included in the systematic review. We discovered a moderate-to-high quality of evidence that ICI was not associated with a higher mortality risk, while the other outcomes yielded a very low-to-low-evidence quality. Although our findings indicated that ICI did not result in a higher risk of severity and hospitalization, further evidence is required to confirm our findings. In addition, we discovered that prior exposure to chemoimmunotherapy may be linked with a higher risk of COVID-19 severity (OR 8.19 [95% CI: 2.67–25.08]; I2 = 0%), albeit with small sample size. Conclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased in such patients. Further studies with larger cohorts and higher quality of evidence are required to substantiate our findings. Trial registration number This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02990-9.

Background : We investigated the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) and its correlation with fibrosis and steatosis as reflected in the controlled attenuation parameter and transient elastography valuesMethods : A cross-sectional study was performed on 37 patients with NAFLD at Cipto Mangunkusumo National General Hospital from December 2018 to March 2019. The gut microbiota was investigated in fecal samples with 16S RNA sequencing using the next-generation sequencing platform MiSeq (Illumina).Results : NAFLD was more common in patients with metabolic syndrome. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla. Bacteroides was more dominant than Prevotella, contrary to the results in previous studies on normal populations in Indonesia. Microbiota dysbiosis was observed in most samples. The gastrointestinal microbiota diversity was significantly decreased in patients with NAFLD with high triglyceride levels and central obesity. The Firmicutes/Bacteroidetes ratio correlated with steatosis and obesity, whereas some other species in the lower taxonomy were mostly correlated with steatosis and obesity without fibrosis. Proteobacteria is the only phylum strongly correlated with fibrosis in patients with normal body mass index.Conclusions : The gut microbiota diversity was decreased in patients with NAFLD with high triglyceride levels and central obesity, and certain gut microbes were correlated with fibrosis and steatosis.

Background: Fms-like tyrosine kinase-3, internal tandem duplication (FLT3-ITD) mutation, is a known predictor for worse outcome in patients with acute myeloblastic leukemia (AML). However, the prognostic significance of FLT3-ITD mutation in adult, non-transplant patients is still unclear therefore we conducted a systematic review and meta-analysis to explain this issue. The main outcome was overall survival (OS), while additional outcomes included event-free survival (EFS). Methods: Seven Databases (ScienceDirect, Scopus, PubMed, Cochrane, SpringerLink, ProQuest, and EBSCOhost) were searched up to August 2020. Studies investigating the prognostic value of AML in adults with FLT3-ITD mutational status were selected. Studies which patients had received transplantation, diagnosed with acute promyelocytic leukemia (APL) or secondary AML were excluded. The selected studies were divided into subgroups based on their cytogenetic profile. Summary hazard ratios (HR) and 95% confidence intervals (CI) were calculated using fixed-effects models. Heterogeneity tests were conducted and presented in I2 value. Forest plot was presented to facilitate understanding of the results. Publication bias was analyzed by Funnel Plot test. Results: A total of ten studies describing research conducted from 1999 to 2020, met the inclusion criteria for this study. Nine studies reported OS and four studies reported EFS in HR. The highest HR for OS is 6.33 (95% CI, 2.61-15.33; p < 0.001), for EFS is 3.58 (95% CI, 1.59 – 8.05); p = 0.002)., while the lowest for OS is 1.33 (95% CI, 0.88-2.01; P = 0.174) and for EFS is 1.29 (95% CI, 0.75-2.23; p = 0.34). Nine studies were included in meta-analysis with HR for OS 1.91 (95% CI, 1.59–2.30, p < 0.00001), whereas 4 studies were included in meta-analysis for EFS with HR 1.64 (95% CI, 1.25–2.14; p = 0.0003). Conclusion: FLT3-ITD mutation is associated with worse prognosis in adult, non-transplant patients with AML, both for OS and EFS.

Background The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. In Indonesia Hasan, I et al. (2002) reported the prevalence of 30.6%. This study evaluated the first time the profile of gut microbiota and correlation with severity of NAFLD in Indonesia. Methods We included 37 subjects age 18–60 years. The characteristic data of the patients and the food recalls were recorded. Abdominal ultrasound, liver transient elastography with controlled attenuation parameter (CAP) were performed. Next generation 16S rRNA metagenomic sequencing was conducted using stool samples. The Spearman correlation test was used to examine the correlation between specific microbial taxa with the severity of NAFLD based on fibrosis and steatosis degree. Results The subjects included 62.2% (n=23) females and 37.8% males (n=14), mean age 50 ± 7.93 years old. They were divided based on fibrosis and steatosis degree into non-significant and significant fibrosis using cut off 7 KPa, mild and moderate-severe steatosis based on cut off 270 dB/m. From all subjects, we got 73% vs 27% non-significant and significant fibrosis, 51.4% vs 48.6% mild and moderate-severe steatosis. At the phylum level, the proportion of Bacteriodetes did not change in fibrosis or steatosis group. The proportion of Proteobacteria and Firmicutes was different in fibrosis and steatosis groups. Actinobacteria unknown bifidobacteriales bifidobacteriaceae bifidobacterium Bifidobacterium adolescentis correlate positively with non significant fibrosis (r = 0.532; p=0.004). Firmicutes clostridia clostridiales lachnospiraceae unknown fusicatenibacter saccharivorans and Firmicutes clostridia clostridales ruminococcaceae unknown [clostridium] leptum correlate negatively with significant fibrosis (r = -0.695; p=0.026 vs r = -0.732; p=0.016). In the group of steatosis, we got Bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes onderdonkii and Firmicutes clostridia clostridales oscillospiracea oscillospiraceao scilibacter ruminantum correlate negatively with moderate-severe steatosis (r = -0.478; p=0.045 vs r = -0.518; p=0.028); Bacteroidetes bacteroidia bacteroidales rikenellaceae alistipes alistipes putredinis correlate positively with mild steatosis (r = 0.503; p=0.028). Conclusions The abundance of microbiota in NAFLD are not significantly different based on the group of fibrosis and steatosis, especially in phylum level. But at the lower level, some specific microbiota may correlate with the degree of fibrosis and steatosis.

Pendahuluan . Respons hematologi lengkap merupakan bagian tak terpisahkan dari pencapaian target respons sitogenetik lengkap dan respons molekular mayor terapi imatinib mesylate meskipun tidak menentukan prognosis. Respons hematologi lengkap pasien LGK fase kronik di Indonesia lebih rendah daripada kasus LGK fase kronik di dunia (74% vs. 95,3%). Perbedaan ini karena 60% pasien di Indonesia mendapat hidroksiurea lebih dulu. Penelitian ini bertujuan untuk mengetahui faktor-faktor prognostik apa saja yang memengaruhi respons hematologi lengkap pasien LGK fase kronik yang mendapat imatinib mesylate di Indonesia. Metode . Penelitian dilakukan dengan desain kohort retrospektif menggunakan rekam medis pasien leukemia granulositik kronik yang datang berobat ke Klinik Teratai RSCM dan Poli Hematologi RSCM lantai 2 yang mendapat terapi imatinib mesylate sejak Januari 2004-Desember 2011. Hasil . Sebagian besar subjek penelitian laki-laki (61,5%), berumur 26-40 tahun (47,4%), lama diagnosis

Rheumatoid arthritis (RA) is an autoimmune disease which has recently been recognized to manifest as not only intraarticular but also extraarticular symptoms. Cardiovascular events, presented either subclinically or clinically, were discovered more in AR patients. Atherogenic inflammatory mediator in AR including interleukin-6 (IL-6) was thought to be one of nontraditional cardiovascular risk factor contributing to increase the endothelial dysfunction biomarker such as E-Selectin. This study was purposed to determine the correlation between inflammatory mediator and endothelial dysfunction event, especially between IL-6 and E-Selectin, in RA patient without traditional cardiovascular risk factor. A cross-sectional study was performed to 40 RA patients of Rheumatology Clinic of Cipto Mangunkusumo National General Hospital, Indonesia from September to November 2017. Measurement of the level of IL-6 and E-Selectin were performed using enzyme-linked immunosorbent assay (ELISA). Bivariate correlation analysis was performed to determine the correlation between those two biomarkers. The mean age of this study subjects was 44.9 (13.1) years and median of disease duration was 36 months. This study showed weak correlation between IL-6 and E-Selectin level, but not statistically significant.232, p=0.149). There is weak correlation between IL-6 and sE-Selectin in rheumatoid arthritis patient without traditional risk factor cardiovascular Keywords: traditional risk factor cardiovascular, E-Selectin, interleukin-6, pro inflammatory mediator, rheumatoid arthritis

Background:The mortality of Rheumatoid Arthritis (RA) is quite high, which is largely due to cardiovascular complications caused by endothelial dysfunction. One of the important inflammatory mediators that contribute to RA joints arthritis of TNF-α, also proven to play a role in endothelial dysfunction and play a role in increasing intracellular lipolysis, thus increasing circulating FFA levels.Objectives:To determine the correlation between TNF-α levels with VCAM-1 levels, correlation of TNF-α levels with FFA levels, and correlation of FFA levels with VCAM-1 levels.Methods:Cross sectional and retrospective design studies of adult RA patients treated at Cipto Mangunkusumo Hospital (RSCM), without metabolic disturbances, acute infection, cardiovascular disorders, or other autoimmune diseases. The cross-sectional data was collected from October to November 2017, while retrospective samples were collected since August 2016. TNF-α, VCAM-1, and FFA levels were assessed by serum blood test by ELISA method. Correlation analysis is done by Pearson analysis when the data distribution is normal and with Spearman analysis when the data distribution is not normal.Results:A total of 35 subjects were enrolled in the study. Most (97.1%) were women with an average age of 45.29 years, median disease duration of 48 months, and most had moderate disease activity (65.7%). No significant correlation was found between TNF-α levels and VCAM-1 levels (p = 0.677; r = +0.073). as well betwen TNF-α levels and FFA levels (p = 0.227; r = -0.21). The correlation between FFA and VCAM-1 levels showed significant correlation with negative correlation and weak correlation (p = 0.036; r = -0.355).Conclusions:(1) There was no correlation between TNF-α levels and VCAM-1 levels in RA patients; (2) There was no correlation between TNF-α levels and FFA levels in RA patients; (3) There was a negative correlation between FFA levels and VCAM-1 levels in RA patients.

Aim: To assess CML patient’s characteristic including demographic, clinical and hematological characteristic of patients with CML including quantitative BCR-ABL and BCR-ABL gene sequencing. Methods: This study was an open-label, single arm, non-randomized, cross sectional study in patients with CML being treated with imatinib mesylate (IM) from 12 centers. Result: A total of 100 patients were evaluated between January 1, 2009 and December 31, 2011. The median age was 34-35 years old (mean of age is 36 years old), and more patients in the productive age was found. ------- (?) were 80 of the 100 patients who had been examined for the BCR-ABL gene mutation with the sequencing method before consuming IM. Mutation in the P-loop was seen in 2,27% (1 out of 44 patients), this finding was beyond our expectation since 47,69% (31 out of 65 patients) of our patients did not achieved CHR at three months. On the other hand, 15,9% (7 out of 44 patients) of our patients had mutation outside the P-loop. Conclusions: The characteristics of CML patients in Indonesia were not different from CML patients in Asia in general. Our finding concerning the high frequency mutation in the BCR-ABL gene outside the P-loop needs further study.