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.

Metabolic Profile and Negatively Association Between Insulin Resistance and Metastatic Incidence in Indonesian Primary Invasive Breast Cancer: A Cross-Sectional Study.

Introduction: Metastatic breast cancer was associated with high morbidity and mortality. Insulin resistance was hypothesized to be related to the incidence of advanced breast cancer. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Triglyceride/Glucose Index (TyG Index) are two metrics used to measure the degree of insulin resistance. This study aims to assess the relationship between the incidence of metastatic breast cancer and insulin resistance as reflected by both metrics. Material and Methods: This study is a cross-sectional study involving 150 primary invasive breast cancer patients recruited from two hospitals of different sectors from August 2019 to April 2020. Patients with double cancer and autoimmune disorder were excluded from this study. Data obtained from the patients include age, body mass index (BMI), type 2 diabetes mellitus (T2DM) status and treatment, and low-density lipoprotein (LDL) cholesterol. The electronic medical records (EMR) was consulted to find histopathology examination result, cancer staging, and any missing data. The association between HOMA-IR and TyG with metastatic incidence was analyzed using either the Mann-Whitney test (for non-normally distributed data) or the independent-sample t-test (for normally distributed data). Results: The mean of the TyG index is 8.60, and the median of HOMA-IR is 1.22. We found no significant correlation between both variables and the incidence of metastases. Conclusion: Insulin resistance was not associated with metastatic breast cancer.

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.

Efficacy of COVID convalescent plasma therapy in hospitalized moderate coronavirus disease 2019 patients.

INTRODUCTION: Covid Convalescent Plasma (CCP) failed to demonstrate its efficacy in severe and life-threatening coronavirus disease 2019 (COVID-19) cases. However, the role of CCP in hospitalized moderate cases is unclear. This study aims to examine the efficacy of administering CCP to hospitalized moderate coronavirus disease 2019 patients. METHODOLOGY: An open-label randomized controlled clinical trial design was used from November 2020 - August 2021 at two referral hospitals in Jakarta, Indonesia, and the primary outcome was mortality at 14 days. The secondary outcomes were mortality at 28 days, the time-to-discontinuation of supplemental oxygen, and the time-to-hospital discharge. RESULTS: This study recruited 44 subjects, and the intervention arm consisted of 21 respondents who received CCP. The control arm consisted of 23 subjects who received standard-of-care treatment. All subjects survived during the fourteen-day follow-up period, and the 28-day mortality rate in the intervention group was lower than the control (4.8% vs 13.0%; p = 0.16, HR = 4.39 (95% CI = 0.45-42.71). There was no statistically significant difference in the time-to-discontinuation of supplemental oxygen and time-to-hospital discharge. During the total follow-up period (41 days), the mortality rate in the intervention group was also lower than the control (4.8% vs 17.4%, p = 0.13, HR = 5.47, 95% CI = 0.60-49.55). CONCLUSIONS: This study concluded that in hospitalized moderate COVID-19 patients, CCP did not reduce 14-day mortality compared to the control. Mortality during 28 days and total length of stay (41 days) were lower in the CCP group compared to the control, although they did not reach statistical significance.

The correlation between serum 25-hydroxy-vitamin D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients receiving COVID-19 vaccines.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, vitamin D has been established as an immune-modulator that reduces pro-inflammatory damage which effectively diminish the severity of COVID-19. Vitamin D also has a significant effect against influenza and dengue and increase the seroconversion following influenza vaccination. To date, the role of vitamin D in optimizing the efficacy of COVID-19 vaccines remains unclear. This study aimed to analyze the correlation between serum 25-hydroxy-cholecalciferol or 25(OH)D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients. Methodology: A multicenter cross-sectional study was conducted among solid and hematologic cancer patients who were vaccinated with two doses of the same types of COVID-19 vaccines (either mRNA, non-replicating viral vector, or inactivated) within 6 months. Result: The median serum 25(OH)D level in 119 cancer patients was 36.36 [IQR = 30.30] ng/mL. The seropositivity of S-RBD IgG and NAb reached 93.3 and 94.1%, respectively. The S-RBD IgG level was significantly higher in the sufficient group (median = 414.07 [1,441.83] AU/mL) than in the deficient group (median = 91.56 [652.00] AU/mL) (p-value = 0.049). Among non-chemotherapy subjects, the anti-SARS-CoV-2 S-RBD IgG levels had a significant positive correlation with 25(OH)D levels (p-value = 0.03; R = 0.588). The NAb levels also showed significantly positive correlation with 25(OH)D level (p-value = 0.005; R = 0.561). The 25(OH)D levels were positively correlated with S-RBD IgG levels among subjects younger than 60 years old (p-value = 0.047; R = 0.136). However, serum 25 (OH)D levels showed no such correlation with S-RBD IgG levels among subjects older than 60 years old (p-value = 0.933; R = 0.136). Conclusion: Both anti-SARS-CoV-2 S-RBD IgG and NAb levels developed moderate correlation with 25(OH)D levels among subjects treated without chemotherapy. The S-RBD IgG levels also had positive correlation with 25(OH)D levels among subjects younger than 60 years old. Thus, we recommended cancer patients to maintain serum 25(OH)D levels above 30 ng/mL (75 nmol/L) to enhance the efficacy of COVID-19 vaccines.

How to Diagnose, Treat, and Monitor Treatment Response in Patients with Multiple Myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein production in the serum, and organ dysfunction. It is part of a disease spectrum called plasma cell disorders, and to establish the diagnosis, a bone marrow biopsy should be conducted with clinical signs of end-organ damage and/or significantly elevated monoclonal protein (M-protein). MM can also be diagnosed without end-organ damage when certain conditions are met since the International Myeloma Working Group (IMWG) has come up with new diagnostic criteria for multiple myeloma.Treatment for all patients with MM aims to enhance the depth and duration of response while limiting drug toxicity to lengthen survival, improve quality of life, alleviate symptoms and prevent further organ damage. Development of new drugs has improved the survival of patients4 Available tests for monitoring of patients with MM most often include assessments of monoclonal paraprotein and serum-free light chain levels with bone marrow examination, which directly identifies the level of malignant plasma cells.

The Profile of COVID-19 in Patients with Autoimmune Disease: A Case Series.

Autoimmune diseases are known to be a risk factor for severe COVID-19 infection. This is the first case series of patients with autoimmune disease suffering from COVID-19 infection in Jakarta, Indonesia. There were 12 confirmed cases of COVID-19 infection in autoimmune patients from March 2020 until February 2021. We select 5 patients in this case series. Three of them had systemic lupus erythematous (SLE), one of them had rheumatoid arthritis, and one of them had ankylosing spondylitis. Three of them had high BSR Risk Stratification. Most of them had used daily steroid therapy. Fatigue, abdominal pain, diarrhea, and cough were the common symptoms found.  None of the patients were admitted to ICU, used mechanical ventilators, and all of them survived. Most of the patients were prescribed anti-coagulant therapy. This first comprehensive case series can provide valuable information regarding the clinical characteristics of COVID-19 infection in the Indonesian autoimmune disorder patient population.

Hematologic Profiles and Correlation Between Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio with Markers of Inflammation of COVID-19 in an Indonesian National Referral Hospital.

INTRODUCTION: COVID-19 is a pandemic with significant mortality and it is important to differentiate severe and non-severe cases. We conducted a study to evaluate hematologic profiles with inflammation markers in COVID-19 patients and to determine the correlation of neutrophil-lymphocyte ratio (NLR) with disease severity. METHODS: A cross-sectional study involving hospitalized COVID-19 patients confirmed with a positive SARS-CoV-2 PCR test in Dr. Cipto Mangunkusumo Hospital. Lymphocyte count, NLR, C-reactive protein (CRP) and ferritin were evaluated in severe and non-severe COVID-19 cases at hospital admission. Data was analyzed using Spearman correlation. RESULTS: There were 41 patients aged 20 to 79 years with COVID-19; 33 (80.5%) were non-severe, and 8 (19.5%) were severe cases. There is a statistically significant difference in WBC, relative neutrophils and lymphocytes, NLR, and CRP between non-severe and severe cases. There is a strong correlation between NLR and CRP (r = 0.738; p < 0.001). Our findings show that NLR and absolute lymphocyte count, but not ferritin, play a role in differentiating between non-severe and severe COVID-19 cases. CONCLUSION: In COVID-19 cases, a strong correlation between NLR and CRP might suggest the use of NLR to differentiate between non-severe and severe cases, especially in a remote healthcare facility.

The Relationship between Folic Acid and Vitamin B12 Serum Levels with High Sensitivity C-reactive Protein and Homocysteine in Chronic Hemodialysis Patients: A Cross-sectional Study.

BACKGROUND: Folic acid (FA) and vitamin B12 treatment have been routinely prescribed to lower serum homocysteine levels and to reduce inflammation. However, no study has been conducted to determine serum folic acid (SFA) and vitamin B12 (B12) levels in patients who have twice-weekly hemodialysis. The aim of our study was to assess serum folate and B12  levels in chronic hemodialysis patients and their relationship with hsCRP and homocysteine levels. METHODS: Our study was a cross-sectional study involcing patients who had twice-weekly hemodialysis in Dr Cipto Mangunkusumo National Hospital Jakarta, Indonesia. Predialysis blood samples were taken to measure SFA, B12, homocysteine and hsCRP levels. Patients with medical conditions affecting the assays were excluded. Spearman correlation was used to compare variables. RESULTS: Eighty subjects enrolled in this study. Among those of non-given folic acid and vitamin B-12 supplementation, only 3.85% of subjects had low folic acid levels, and none had low vitamin B12 levels. A moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.42) and a weak correlation between serum vitamin B12 and homocysteine level (p=0.009; r=-0.29) was found. Among the high-risk cardiovascular group (CRP>3, n=49), there is a moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.561) and a weak negative correlation between vitamin B12 and homocysteine level (p=0.018; r=-0.338). CONCLUSION: There is a significant negative correlation between serum vitamin B12 and folic acid with homocysteine levels, especially in high-risk cardiovascular group.

Pulmonary Embolism in Hospitalized Patient with Coronavirus Disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) has been a global pandemic for over a year. Meanwhile, thrombosis occurs in up to one-third of hospitalized patients with the disease, while pulmonary embolism has been reported to be the most dangerous thrombosis which greatly increases mortality in COVID-19.Hospitalized patients with COVID-19 are at high risk of thromboembolic complications such as deep vein thrombosis and pulmonary embolism. The hypercoagulable state caused by COVID-19 leads to activation of coagulation cascade, meanwhile, CT pulmonary angiography is used to diagnose or exclude pulmonary embolism. Furthermore, ground-glass opacities are also evaluated using this modality. Low molecular weight heparin is the anticoagulant of choice due to simplicity in administration and low risk of drug-drug interactions.Pulmonary embolism occurs in COVID-19 patients without DVT. Based on the results, parenteral anticoagulant followed by DOAC is the mainstay of treatment in COVID-19 coagulopathy.

Primary CD20-positive mediastinal diffuse large B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare tumour with different characteristics from other type of lymphomas. Clinical manifestations may vary and cause delay in diagnosis and management. We present a 22-year-old patient with symptoms of shortness of breath, weight loss, and night sweats. Laboratory studies only showed a markedly high lactate dehydrogenase (LDH) level and thoracic computed tomography (CT)scan revealed a large mediastinal mass. Core biopsy-guided CT scan was performed and the pathological and immunohistochemistry established a PMBCL diagnosis. We administered Rituximab Dose-Adjusted Etoposide Prednisolone Vincristine Cyclophosphamide Doxorubicin (R-DA-EPOCH) chemotherapy regimen and the patient responded well to treatment. This is an example of rare case of mediastinal lymphoma with challenges to overcome to achieve diagnostic and therapeutic success. Failure to differentiate PMBCL with other systemic diffuse large B-cell lymphoma (DLBCL) could skew treatment algorithm and prevent optimal response. Administration of proper systemic therapy, especially in young, low-risk patients could yield excellent outcome.