Factors Associated with All-Cause 30-Day Mortality in Indonesian Inpatient COVID-19 Patients at Cipto Mangunkusumo National General Hospital.

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan-Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971-12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048-2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208-9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187-2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279-3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523-86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049-2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092-3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780-6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240-2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.

The risk for post-thrombotic syndrome of subjects with deep vein thrombosis in an Indonesian referral hospital: a retrospective cohort study.

BACKGROUND: Post-thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT) and affects 20-40% of DVT subjects. The risk factor of PTS after DVT is difficult to determine. We aimed to evaluate the incidence of PTS after 3 months of DVT diagnosis and to determine the risk of PTS. METHODS: A retrospective cohort study of subjects who developed DVT confirmed by Doppler ultrasound in Cipto Mangunkusumo Hospital from April 2014 until June 2015. The presence of PTS was assessed after 3 months of completed DVT treatment using the Villalta score. Risk factors for PTS were evaluated from medical records. RESULTS: There were 91 subjects with DVT with mean age of 58 years. 56% were female. It was dominated by subjects aged ≥ 60 years (45.1%). Hypertension (30.8%) and diabetes mellitus (26.4%) were the major comorbidities in this study. Deep vein thrombosis occurred commonly in unilateral side (79.1%), proximal localization (87.9%), and unprovoked DVT (47.3%). The cumulative incidence of PTS after DVT was 53.8%, 69% of subjects had mild PTS. Heaviness of the leg (63.2%) and edema (77.5%) were the most common symptoms. RESULTS: There were 91 subjects with DVT with mean age of 58 years. 56% were female. It was dominated by subjects aged ≥ 60 years (45.1%). Hypertension (30.8%) and diabetes mellitus (26.4%) were the major comorbidities in this study. Deep vein thrombosis occurred commonly in unilateral side (79.1%), proximal localization (87.9%), and unprovoked DVT (47.3%). The cumulative incidence of PTS after DVT was 53.8%, 69% of subjects had mild PTS. Heaviness of the leg (63.2%) and edema (77.5%) were the most common symptoms. Significant risk factors for PTS were unprovoked DVT (adjusted RR 1.67; 95%CI: 1.17-2.04; p = 0.01) and female gender (adjusted RR 1.55; 95%CI: 1.03-1.94; p = 0.04). Age, body mass index, thrombus location, immobilization, malignancy and surgery was not associated with PTS. CONCLUSION: We conclude that 53.8% of subjects suffered PTS after 3 months of DVT. Unprovoked DVT and female gender were significant risk factors for PTS.

A comparative study of the COVID-19 vaccine efficacy among cancer patients: mRNA versus non-mRNA.

BACKGROUND: Cancer patients have an increased risk of a severe COVID-19 infection with higher mortality rate. This study aimed to analyze the levels of anti-SARS-CoV-2 S-RBD IgG and NAB among cancer patients who were vaccinated with COVID-19 vaccines, either with BNT162b2, mRNA-1273, AZD1222/ChAdOx1nCoV-19, or Coronavac/BBIBP-CorV vaccines. METHOD: A cross-sectional study was conducted among subjects with either solid or hematological cancers who had received two doses of either mRNA or non-mRNA vaccines within 6 months. The levels of anti-SARS-CoV-2 S-RBD IgG and NAb were analyzed using the Mindray Immunoassay Analyzer CL-900i. Statistical analysis was conducted using mean comparison and regression analysis. RESULT: The mRNA-1273 vaccine had the highest median levels of S-RBD IgG and NAb, followed by BNT162b, ChAdOx1nCoV-19, and BBIBP-CorV/Coronavac. The levels of S-RBD IgG and NAb in subjects vaccinated with mRNA vaccines were significantly higher than those of non-mRNA vaccines when grouped based on their characteristics, including age, type of cancer, chemotherapy regimen, and comorbidity (p<0.05). Furthermore, the S-RBD IgG and NAb levels between the subjects vaccinated with non-mRNA vaccines and the subjects vaccinated with mRNA vaccines were significantly different (p<0.05). However, there was no significant difference between the same types of vaccines. This study demonstrated a very strong correlation between the level of S-RBD IgG and the level of NAb (R = 0.962; p<0.001). The level of anti-SARS-CoV-2 S-RBD IgG was consistently higher compared to the level of NAb. CONCLUSIONS: Generally, mRNA vaccines produced significantly higher anti-SARS-CoV-2 S-RBD IgG and NAb levels than non-mRNA vaccines in cancer subjects.

Clinical Characteristics and Prognostic Risks of Philadelphia-Negative Myeloproliferative Neoplasms at Cipto Mangunkusumo General Hospital.

Background: Philadelphia-negative myeloproliferative neoplasms (Ph-MPNs) are clonal hematopoietic cell malignancy that comprises polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). They prone to develop thrombosis, bleeding, fibrotic progression, and leukemic transformation. We aimed to study clinical characteristics, thrombosis complications, and prognostic risk in Indonesians with Ph-MPNs. Methods: This was a single-center retrospective cross-sectional study, including patients with Ph-MPNs who attended Hematology and Medical Oncology outpatient clinic at Cipto Mangunkusumo General Hospital, Jakarta, between 2016 and 2021. Demographic data, clinical characteristics, previous antiplatelet treatment, baseline laboratory data, JAK2V617F mutation, and treatment were reviewed for analysis. The prognostic risk model was assessed for PV (IPSS), ET (IPSET-thrombosis), and PMF (IPSS and DIPPS) patients. Results: One hundred forty-six patients were classified as PV (31.5%), ET (38.4%), and PMF (30.1%) with median ages of 54, 53.5, and 55 years, respectively. PMF presented with the most diverse clinical presentations. JAK2V617 mutations were detected in 82%, 42.5%, and 76.5% of PV, ET, and PMF patients. PV had the highest thrombosis event pre/at diagnosis (26.1%), with predominantly arterial thrombosis. Bleeding occurred more in PMF (20.5%). Phlebotomy and hydroxyurea are the only treatment available for Ph-MPNs in the government hospital in Indonesia. IPSS intermediate risk in PV (47.8%), IPSET-thrombosis low risk in ET (46.4%), and IPSS and DIPSS intermediate-2 in PMF (38.6% and 50% respectively) were the most common risk groups. Conclusion: Essential thrombocythemia was the most prevalent Ph-MPNs in Indonesia. Arterial thrombosis was the highest thrombosis event pre/at diagnosis in PV despite IPSET-thrombosis low risk being the most common risk group. In JAK2V617 mutation-positive MPN population, thrombosis event was also the highest in PV.

Diagnosis of Chronic Lymphocytic Leukemia Using iwCLL 2018 Compared with NCI-WG96 Criteria in Cipto Mangunkusumo Hospital: A Practical Consideration in Resource Limited Setting.

BACKGROUND: The diagnosis of chronic lymphocytic leukemia (CLL) is mainly based on blood count, morphology, and immunophenotyping. In Indonesia, the diagnosis is more challenging as the availability of immunophenotyping tests is limited. The European Society of Medical Oncology (ESMO) stated flowcytometry as a prerequisite to establishing diagnosis of CLL, meanwhile in the original International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria, which has been widely accepted by physicians caring for patients with CLL,  the diagnosis of CLL can be made in patients with cytopenia using bone marrow biopsy where flowcytometry test is not available. The aim of the study was to compare the utility of International Workshop on Chronic Lymphocytic Leukemia 2018 [iwCLL 2018 (2)] compared with National Cancer Institute Working Group 96 (NCI-WG96) criteria in the diagnosis of CLL in Indonesia, especially in limited resource settings. METHODS: The data of newly diagnosed CLL patients, including baseline demographic, clinical, and laboratory characteristics was retrieved retrospectively from medical records in Cipto Mangunkusumo General Hospital from 2015 until 2021. Diagnosis of CLL  using iwCLL 2018 diagnostic criteria were then compared with National Cancer Institute Working Group 96 (NCI-WG96) criteria.  Results: Thirty-eight patients were enrolled to this study. The median age was 59.5 years and dominated by males. Most of them were classified in the late-stage disease (63.4% in Binet C and about 70% in Rai III-IV). Four cases were CD5-negative CLL. Based on NCI-WG96 guideline, only 24 patients (63.2%) fulfilled all four criteria for CLL. Similarly, using the iwCLL 2018 flowcytometric criteria without biopsy data, 26 patients (68%) were diagnosed as CLL.   However, if bone marrow biopsy in patient with cytopenia was taken into account, all patients (100%) can be confirmed as CLL. CONCLUSION: The iwCLL 2018 criteria which included bone marrow biopsy in the presence of cytopenia was more applicable to establish the diagnosis of CLL in Indonesia where flowcytometry is not available.

Soluble P-selectin and correlation with Prothrombin Fragment 1 + 2 in myeloid malignancies in Cipto Mangunkusumo general hospital.

BACKGROUND: Myeloid cells express microparticles that could increase the expression of adhesion molecules including P-selectin. We aimed to evaluate the level of soluble P-selectin (sP-selectin) and prothrombin fragment 1 + 2 (F1 + 2), and to determine correlation of sP-selectin with leukocyte count and F1 + 2 levels in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. METHODS: Patients with newly diagnosed AML (n = 25), CML (n = 13), and controls (n = 17) were recruited in this study. The diagnosis of AML and CML is based on 2001 WHO and/or FAB criteria. Levels of sP-selectin and F1 + 2 were determined using enzyme-linked immunosorbent assay kits (Behring ELISA Processor-III® and Behring Enzygnost F1 + 2). RESULTS: sP-selectin was significantly elevated in CML patients compared to AML patients (p = 0.001). Levels of F1 + 2 in AML and CML patients were significantly increased in comparison to controls (p < 0.001 and p = 0.043). Levels of sP-selectin were significantly correlated to leukocyte count (r = 0.437; p = 0.029) and F1 + 2 (r = 0.436; p = 0.029) in AML patients. CONCLUSIONS: AML and CML patients had an increased tendency to thrombosis. While CML patients had higher platelet and/or endothelial activation, hypercoagulable state are more pronounced in AML patients.

Comparison between PRP and PRFM on FTSG healing profile: Macroscopic, microscopic and ELISA evaluation.

BACKGROUND: Studies had shown the benefit of PRFM and PRP in wound healing but their use in skin graft healing was rarely studied. This study aims to compare the use of PRP and PRFM in accelerating wound healing process of skin full-thickness skin graft (FTSG). MATERIALS AND METHODS: Five pigs were used to look at the wound healing effect of PRP and PRFM usage prior to FTSG implantation. Subsequent punch biopsies were then conducted on the 1st, 3rd, 7th, 14th, and 30th day to obtain samples for macroscopic (skin color), extracellular matrix (collagen), microscopic (PMN, macrophage, and fibroblast), and ELISA (TGFß1 and PDGF) analysis to determine the level of wound healing activity. ImageJ software was used to photograph for macroscopic and extracellular matrix analysis. RESULTS: Macroscopic, extracellular matrix, and ELISA evaluation show no significant difference in FTSG survival rates for all treatment groups. Microscopic examination showed an increase in PMN, macrophage, and fibroblast levels with PRFM application showing higher increases in all observed microscopic variables compared to PRP and control. CONCLUSION: This study observed that both PRFM and PRP as autologous platelet preparation accelerate wound healing in FTSG, with PRFM being superior due to the higher number of PMN, macrophage, and fibroblast.

IDENTIA Registry: Incidence of Deep Vein Thrombosis in Medically Ill Subjects at High Risk in Indonesia: A Prospective Study.

BACKGROUND: medically ill hospitalized patients are at risk of deep vein thrombosis (DVT) and consequentially have high chances of mortality. In Indonesia, there is disparity in healthcare facility and data on incidence of DVT in this multi-ethnic, geographically unique country with large population are limited. Hence, we determined the incidence of DVT and evaluated mean Wells score among medically ill hospitalized persons at increased risk. METHODS: in this multicenter, prospective, observational registry in Indonesia, subjects (age >40 years) with acute medical illness (like cancer, acute infection, or severe respiratory disease) confined to bed for >3 days were enrolled between January 2016 and November 2017. Data for medical history, Wells score, and DVT diagnosis with compression ultrasonography (CUS) were recorded. DVT incidence was analyzed in eligible and evaluable groups. Data were analyzed by descriptive method. RESULTS: out of 360 subjects enrolled, 334 were included in the eligible group for analyses. CUS could not be performed in 26 subjects. Thus, 308 subjects who completed the study were included in the evaluable group. Javanese were predominant in the eligible group and obesity was the most common medical history at presentation. Overall, incidence of DVT in eligible and evaluable patients was 37.1% and 40.3%, respectively. Mean (SD) Wells score and bedridden days were 3 (1.20) and 9 (6.89), respectively. CONCLUSION: this study indicated that the incidence of DVT is high in medically ill patients in Indonesia and will provide new insights and awareness about DVT in Indonesia.

Higher cut-off serum procalcitonin level for sepsis diagnosis in metastatic solid tumor patients.

OBJECTIVE: The current study aimed to know procalcitonin levels in patients with metastatic tumor, and to discover the cut-off point for sepsis in this population. A cross-sectional study was conducted with patients with solid tumor. Sepsis and systemic inflammation response syndrome (SIRS) were identified using clinical, laboratory, and microbiological criteria. The cut-off point was determined using receiver operating characteristic (ROC) curve. RESULTS: A total of 112 subjects enrolled in this study, 51% male, mean age 47.9 ± 12.47 years. Among 71 (63.4%) patients who had metastasis, 36 (32.1%) had sepsis and 6 (5.3%) experienced SIRS. In the absence of sepsis, the procalcitonin levels were significantly higher in patients with metastatic tumor compared to those without [0.25 ng/mL (0.07-1.76) vs. 0.09 ng/mL (0.03-0.54); p < 0.001]. The ROC curve showed that levels of procalcitonin for sepsis in metastatic solid tumors were in the area under curve (AUC) [0.956; CI 0.916-0.996]. Cut-off point of procalcitonin for sepsis was 1.14 ng/mL, Sn 86%, and Sp 88%. Thus, the results show that metastatic tumor affects the patients' procalcitonin level, even in the absence of sepsis. The cut-off point of procalcitonin level for diagnosing sepsis in the meta-static solid tumor was higher compared to the standard value.

Integrative Approach in Haemophillic Arthropathy of The Knee: a Case Report.

Haemophilic arthropathy is the most prevalent joint disorder in haemophilia. This disorder is characterized by chronic synovitis and progressive destruction of joint cartilage. We report a case of arthroscopic synovectomy to reduce bleeding frequency in haemophilic arthropathy of the knee. Patient was a 15 years old male with haemophilic arthropathy of the left knee. We performed an arthroscopic synovectomy under tightly regulated factor VIII replacement therapy. There were villous synovial hypertrophy at all part of the joint, multiple bone and cartilage defect, and also anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) deficiency found intraoperatively. After 6 month follow up, subjective complain and bleeding frequency decreased significantly. The visual analog scale improved from 5-6 to 1-2, and the International Knee Documentation Committee Score increased from 49 to 66. Bleeding frequency decreased from 4-8 times per month to less than 1 time per month. Arthroscopic synovectomy performed in this case could reduce the pain, decrease the frequency of bleeding, and improve patient's functional outcome.

Pelvic haemophilic pseudotumour: a case report.

We report on a 30-year-old haemophilic man with a pelvic pseudotumour compressing adjacent structures causing pain and swelling and destruction of surrounding soft tissues and bones. He underwent evacuation of the pseudotumour, acetabular reconstruction using the Harrington procedure, and total hip arthroplasty.