Anti-SARS-CoV-2 antibody dynamics after primary vaccination with two-dose inactivated whole-virus vaccine, heterologous mRNA-1273 vaccine booster, and Omicron breakthrough infection in Indonesian health care workers.

BACKGROUND: Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. METHODS: We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. RESULTS: Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28-90, and IgG titers plateaued between day 90-360. During the BA.1/BA.2 wave (February-March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. CONCLUSIONS: mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.

MPox Skin Lesions.

Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.

Diagnostic Accuracy of Serum Procalcitonin to Diagnose Sepsis in Advanced Solid Tumor Patients with Fever.

BACKGROUND: Diagnosis of infection in advanced solid tumor patients can be challenging since signs and symptoms might be overlapping due to paraneoplastic condition. Delay diagnosis of existing infection can lead to more severe conditions and increased mortality. Procalcitonin (PCT) has been used to support the diagnosis of bacterial infection and sepsis. Unfortunately, PCT also increases in malignancy even without an infection. We investigated the diagnostic accuracy of PCT in advanced solid tumor patients with fever to diagnose sepsis. METHODS: A cross-sectional study was conducted in solid advanced tumor patients with fever patients who were admitted to Cipto Mangunkusumo Hospitals, Indonesia between June 2016 and April 2018. Sepsis was defined using 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference criteria. The diagnostic accuracy of PCT was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 194 subjects were enrolled in this study. 60.3% were female with a mean age of 49.47±12.87 years old. 143 patients (73.7%) with advanced solid tumors. Among this latter group, 39 patients (27%) were sepsis. The ROC curve showed that the levels of PCT for sepsis in advanced solid tumor patients with fever were in the area under the curve (AUC) 0.853 (95%CI 0.785 - 0.921). The Cut-off of PCT in advanced solid tumor patients with fever to classify as sepsis was 2.87 ng/mL, with a sensitivity of 79.5%, and a specificity of 79.8%. CONCLUSION: PCT has good diagnosis accuracy in advanced solid tumor patients with fever to classify as sepsis, however a higher cut-off compared to non-cancerous patients should be used.

Multidrug-Resistant Bacteria Colonization in Patients Admitted to Dr. Cipto Mangunkusumo Hospital Jakarta, Indonesia.

BACKGROUND: Antibiotic resistance is the main problem in infectious disease management. Multidrug-resistant (MDR) bacteria could be carried by admitted patients and become a source of spread in the hospital, causing infections in other patients or the patients themselves. However, the screening of MDR bacteria has not been a standard in developing countries. This study aimed to get the prevalence of MDR bacteria colonization in patients on admission to Dr. Cipto Mangunkusumo Hospital. METHODS: Selective liquid media with added antibiotics were used for culturing the MDR bacteria. While admitted to the hospital, subjects were sampled and interviewed to fill out a questionnaire. The screening specimens used for this study were throat, navel, rectal, nasal, and armpit swabs. During hospitalization, hospital-acquired infections (HAIs) were recorded. RESULTS: Of 100 patients included in the study, the prevalence of MDR bacteria colonization on admission was 63% (n=63) with the prevalence of CR-GNB, ESBL-PE, and MRSA were 11%, 54%, and 11%, respectively. Two-thirds of the patients with HAIs (n=8/12) were colonized with MDR bacteria. Factors associated with MDR bacteria colonization were the recent use of invasive medical devices and comorbidity, while a factor associated with CR-GNB colonization was the recent use of antibiotics. CONCLUSION: The prevalence of MDR bacteria colonization in patients on admission to Dr. Cipto Mangunkusumo Hospital in 2022 was 63% (n=63), of which 12.68% (n=8) experienced HAIs during hospitalization. MDR bacteria colonization was associated with the recent use of invasive medical devices and comorbidity. History of antibiotic use was associated with CR-GNB colonization.

Identifying Predictors of Mortality in Sepsis Patients with Malignancy: A Retrospective Cohort Study.

BACKGROUND: Sepsis is a major problem that contributes to a high mortality rate. Its mortality is especially high in patients with malignancy. One study reported that sepsis patients with malignancy have a 2.32 times higher risk of mortality compared to patients without malignancy. For this reason, factors that influence mortality in sepsis patients with malignancy become especially important to provide effective and efficient therapy. This study aims to identify factors that influence mortality in sepsis patients with malignancy. METHODS: This study is a retrospective cohort study using medical records of sepsis patients with malignancy who were treated at Cipto Mangunkusumo Hospital from 2020 to 2022. A bivariate analysis was carried out and followed by a logistic regression analysis on variables with p-value<0.25 on the bivariate analysis. RESULTS: Among the 350 eligible sepsis subjects with malignancy, there was an 82% mortality rate (287 subjects). Bivariate and multivariate analyses revealed significant associations between mortality and both SOFA score (adjusted Odds Ratio of 5.833, 95%CI 3.214-10.587) and ECOG performance status (adjusted Odds Ratio of 3.490, 95%CI 1.690-7.208). CONCLUSION: SOFA score and ECOG performance status are significantly associated with sepsis patient mortality in malignancy cases.

The correlation of anxiety and depression with C3 and C4 Levels and systemic lupus erythematosus activity.

BACKGROUND: Anxiety and depression are psychosomatic disorders that are frequently observed in chronic conditions such as systemic lupus erythematosus (SLE). Anxiety and depression can be induced by immunological and neurotransmitter dysregulation, which is characterized by hypothalamic-pituitary-adrenal (HPA) axis dysfunction, production of proinflammatory cytokines, and activation of complement in the blood, such as C3 and C4. The causes of anxiety and depression in SLE are complex, ranging from neuropsychiatric involvement to drug adverse effects. Detecting anxiety and depression symptoms in SLE patients is critical to preventing disability from impacting quality of life. OBJECTIVE: To assess the relationship between anxiety and depression symptomatology, SLE disease activity with levels of C3 and C4 in Cipto Mangunkusumo National Hospital. METHODS: This study used a cross-sectional design. The study included 120 SLE patients from Cipto Mangunkusumo National Hospital, aged 18 to 60 years. All patients were requested to complete a Hospital Anxiety and Depression Scale (HADS) questionnaire to assess their anxiety and depression symptoms. Subjects with anxiety and depression were assessed for disease activity using the Mexican Systemic Lupus Erythematosus Systemic Disease Activity (Mex-SLEDAI), and blood samples were collected to test complement C3 and C4 levels. Spearman's correlation test was used to examine the relationship between HADS scores, Mex-SLEDAI, and C3 and C4 levels. RESULTS: The results of the study showed a very weak statistically significant negative correlation between anxiety symptoms based on HADS and C3 levels (r = -0.189; p = 0.038) and a weak correlation between anxiety symptoms and C4 levels (r = -204; p = 0.026). Depressive symptoms based on HADS revealed a very poor connection and no statistical significance with levels of C3 (r = -0.056; p = 0.546) and C4 (r = -0.068; p = 0.461). Anxiety (r = 0.06; p = 0.173) and depression (r = 0.031; p = 0.753) symptoms have a weak and insignificant positive connection with SLE activity. CONCLUSION: C3 and C4 serum levels appeared to decrease when the presence of anxious symptoms increased. There was no significant correlation in SLE disease activity between anxious and depressed patients.

Diagnostic accuracy of palpation versus ultrasound-guided fine needle aspiration biopsy for diagnosis of malignancy in thyroid nodules: a systematic review and meta-analysis.

Thyroid nodule is a common health problem in endocrinology. Thyroid fine-needle aspiration biopsy (FNAB) cytology performed by palpation guided FNAB (PGFNAB) and ultrasound-guided FNAB (USGFNAB) are the preferred examinations for the diagnosis of thyroid cancer and part of the integration of the current thyroid nodule assessment. Although studies have shown USGFNAB to be more accurate than PGFNAB, inconsistencies from several studies and clinical guidelines still exist.The purpose of this study is to compare the diagnostic accuracy of Palpation versus Ultrasound-Guided Fine Needle Aspiration Biopsy in diagnosing malignancy of thyroid nodules.The systematic review and meta-analysis were prepared based on the PRISMA standards. Literature searches were carried out on three online databases (Pubmed/MEDLINE, Embase, and Proquest) and grey literatures. Data extraction was carried out manually from various studies that met the eligibility, followed by analysis to obtain pooled data on sensitivity, specificity, Diagnostic Odds Ratio (DOR) and Area Under Curve (AUC), and the comparison of the two methods.Total of 2517 articles were obtained, with 11 studies were included in this systematic review. The total sample was 2382, including 1128 subjects using PGFNAB and 1254 subjects using USGFNAB. The risk of bias was assessed using QUADAS-2 with mild-moderate results. The results of sensitivity, specificity, AUC and DOR in diagnosing thyroid nodules using PGFNAB were 76% (95% CI, 49-89%), 77% (95% CI, 56-95%), 0.827 and 11.6 (95% CI, 6-21) respectively. The results of sensitivity, specificity, AUC and DOR in diagnosing thyroid nodules using USGFNAB were 90% (95% CI, 81-95%), 80% (95% CI, 66-89%), 0.92 and 40 (95% CI, 23-69), respectively the results of the comparison test between PGFNAB and USGFNAB; Tsens USGFNAB of 0.99 (p = 0.023), AUC difference test of 0.093 (p = 0.000023).The diagnostic accuracy of USGFNAB is higher than PGFNAB in diagnosing malignancy of thyroid nodules. If it is accessible, the author recommends using USGFNAB as a diagnostic tool for thyroid nodules.

COVID-19 Pandemic-to-Endemic Transition in Indonesia: What Does the Future Hold?

Since first reported in December 2019, SARS-2 Coronavirus (SARS-CoV-2) infection has become a world-class pandemic, overwhelming every aspect of the global system. Globally, 526 billion confirmed cases with 6,3 billion death cases were reported by World Health Organization (WHO) by 31 May 2022. In that period, Indonesia has reported 6 billion confirmed cases with a case fatality rate reaching 2.58%. The number of new weekly cases and new weekly death have continued the declining trend observed since its peak in January 2022, i.e. 3% decrease of new weekly cases and 11% decrease of new weekly death as compared to the previous week. In response to the current epidemiology improvement, countries including Indonesia have relaxed some regulations on COVID-19 as the preparation for pandemic-to-endemic transition.Endemic is not equal to harmless. Commonly, endemic is falsely interpreted as the end of COVID-19, bringing to a false complacency. Endemic "label" on an infectious disease, such as malaria, HIV infection, tuberculosis in certain regions of the world, means the overall rates of infection are static - neither rising nor falling. Endemic "label" defines nothing about time duration to reach disease end or how many populations will still be susceptible to the disease. Therefore, transition for pandemic-to-endemic of COVID-19 could not simply translated into the end of either public and health service awareness, or research on COVID-19. It then should add new emerging perspective on COVID-19 research as was mandated by WHO. One example of which is evidence-based strategies for infection prevention control and personal protective equipment for infection control de-escalation in relation to COVID-19 pandemic scaling back.In the spirit of nurturing research and publication in this transition for pandemic-to-endemic era, the Indonesian Journal of Internal Medicine published various COVID-19 associated-original articles, systematic review, and case series across various COVID-19 condition. Atici, et. al. and Tunjungputri, et. al. report articles on factors and treatment that is associated with higher COVID-19 survival. Corticosteroids, Interleukin-6 inhibitors and anticoagulant administered to the proper subset of COVID-19 population are several beneficial treatments among limited evidence-based proven treatment available today. These supportive treatments, whenever indicated at the proper time, should be considered in managing every COVID-19 patient. In addition, high antibiotic use in COVID-19 patients despite low secondary bacterial infection has been widely reported. Chen, et. al. report a similar situation in Indonesia and should raise the awareness of antimicrobial resistance thread now and in the future. Together with proper diagnostic stewardship, the simple predictors of secondary bacterial infection that have been concluded could potentially be used to reduce liberal antibiotic use while optimizing the use in indicated patients. Prabowo, et al. enriched our understanding on usage of telemedicine to monitor post COVID-19 condition in Indonesian populations.High quality research has, and will again, save the livelihoods of people across the world. While future pandemics could not be completely prevented, the research infrastructures that have built during last 2 years could be used as a strong modality to be better prepared and coordinated in future outbreak/ pandemic response by detecting and preventing the emerging diseases at their very early stage. Waste in COVID-19 research and multiple COVID-19 associated research article retractions should caution researchers -as evidence-producer- and clinicians -as evidence-user- in prioritizing the scientific inquiry and questioning individual conflict of interest. Insightful articles addressing the multitude aspects of the COVID-19 pandemic-to-endemic transition related topics are still needed in the future.

Observational Study on Secondary Bacterial Infection and the Use of Antibiotics in COVID-19 Patients Treated in a Tertiary Referral Hospital.

BACKGROUND: Data on secondary bacterial infection in patients with COVID-19 in Indonesia are still limited, while the use of empirical antibiotics continues to increase. This study aims to determine the secondary bacterial infection rate in hospitalized COVID-19 patients and factors related to secondary bacterial infection. METHODS: This is a retrospective cohort study on hospitalized COVID-19 patients undergoing treatment at Cipto Mangunkusumo Hospital from March 2020 to September 2020. Secondary bacterial infection is defined as the identification of a bacterial pathogen from a microbiological examination. RESULTS: From a total of 255 subjects, secondary infection was identified in 14.5%. Predictors of secondary infection were early symptoms of shortness of breath (OR 5.31, 95% CI 1.3 - 21.5), decreased consciousness (OR 4.81, 95% CI 1.77 - 13.0), length of stay > 12 days (OR 8.2, 95% CI 2.9 - 23.3), and central venous catheter placement (OR 3.0, 95% CI 1.1 - 8.0) The most common pathogen of secondary bacterial infection is Acinetobacter sp. (n=9; 28%). Empirical antibiotics were administered to 82.4% of subjects with predominant use of macrolides (n=141; 32.4%). CONCLUSION: The secondary bacterial infection rate in COVID-19 was 14.5% and is associated with dyspnea, decreased consciousness, length of stay >12 days, and central venous catheter placement. The use of antibiotics in COVID-19 reaches 82.4% and requires special attention to prevent the occurrence of antibiotic resistance.

Molnupiravir and Nirmatrelvir/Ritonavir: The New Available Antiviral Options for COVID-19.

Coronavirus disease 2019 (COVID-19) is a respiratory tract disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the complexity of multimorbidity in Indonesia, it is crucial to find another line of antiviral for COVID-19. This article aims to review two antivirals, molnupiravir and nirmatrelvir/ritonavir, that have been studied extensively in treating COVID-19 with promising results, and their availability in Indonesia. Molnupiravir and nirmatrelvir/ritonavir are two of many repurposed drugs in clinical trials, which have been reported to have a mechanism in quick clearance of SARS-CoV-2, reduction in viral load, and fast symptoms recovery time in phase 1 and 2 clinical trials. Phase 2/3 clinical study in COVID-19 patients without any indication for hospitalization showed that molnupiravir and nirmatrelvir/ritonavir significantly reduced the risk of hospitalization and death.

Revisiting the Overlooked Infection: Rickettsioses.

The prevalence of human Rickettsioses cases in Indonesia is unknown and could probably be underestimated. The high prevalence of seropositive Rickettsia sp. was reported in small mammals (as vectors) and humans. In Indonesia, a recent study in patients with acute fever revealed that the prevalence of Rickettsioses is 10%. Many cases of Rickettsioses were often misdiagnosed with dengue fever, enteric fever, or leptospirosis due to their overlapping clinical manifestation. The limitation of point of care testing in Indonesia hindered the adequacy of diagnosis confirmation. Appropriate empirical or definitive treatment with macrolide, mainly doxycycline, is preferable compared to other broad-spectrum antibiotics, such as cephalosporin or quinolones. Moreover, when left untreated, Rickettsioses may deteriorate progressively to fatal outcomes, such as meningitis, sepsis, and even death. The awareness of health care practitioners, the availability of confirmatory rapid diagnostic tests and adequate treatment choices are important in eradicating this disease.

Prognostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA)-lactate criteria for mortality in adults with suspected bacterial infection in the emergency department of a hospital with limited resources.

BACKGROUND: Routine use of the Sequential Organ Failure Assessment (SOFA) score to prognosticate patients with sepsis is challenged by the requirement to perform numerous laboratory tests. The prognostic accuracy of the quick SOFA (qSOFA) without or with lactate criteria has not been prospectively investigated in low and middle income countries. We assessed the performance of simplified prognosis criteria using qSOFA-lactate criteria in the emergency department of a hospital with limited resources, in comparison with SOFA prognosis criteria and systemic inflammatory response syndrome (SIRS) screening criteria. METHODS: This prospective cohort study was conducted between March and December 2017 in adult patients with suspected bacterial infection visiting the emergency department of the Indonesian National Referral Hospital. Variables from sepsis prognosis and screening criteria and venous lactate concentration at enrolment were recorded. Patients were followed up until hospital discharge or death. Prognostic accuracy was measured using area under the receiver operating characteristic curve (AUROC) of each criterion in the prediction of in-hospital mortality. RESULTS: Of 3026 patients screened, 1213 met the inclusion criteria. The AUROC of qSOFA-lactate criteria was 0.74 (95% CI 0.71 to 0.77). The AUROC of qSOFA-lactate was not statistically significantly different to the SOFA score (AUROC 0.75, 95% CI 0.72 to 0.78; p=0.462). The qSOFA-lactate was significantly higher than qSOFA (AUROC 0.70, 95% CI0.67 to 0.74; p=0.006) and SIRS criteria (0.57, 95% CI0.54 to 0.60; p<0.001). CONCLUSIONS: The prognostic accuracy of the qSOFA-lactate criteria is as good as the SOFA score in the emergency department of a hospital with limited resources. The performance of the qSOFA criteria is significantly lower than the qSOFA-lactate criteria and SOFA score.This abstract has been translated and adapted from the original English-language content. Translated content is provided on an "as is" basis. Translation accuracy or reliability is not guaranteed or implied. BMJ is not responsible for any errors and omissions arising from translation to the fullest extent permitted by law, BMJ shall not incur any liability, including without limitation, liability for damages, arising from the translated text.

Comparison of Survival Prediction with Single versus Combination Use of Microcirculation End Point Resuscitation in Sepsis and Septic Shock.

BACKGROUND: lactate clearance and central venous oxygen saturation (ScvO2) are two methods for determining tissue oxygenation adequacy. There is a controversy regarding method better associates with and predicts sepsis and septic shock patients' mortality. This study address the association of achieving one or two targets of microcirculatory resuscitation endpoints and early mortality in sepsis and septic shock. METHODS: a cohort study was conducted in adult sepsis and septic shock patients in Intensive Care Unit, Cipto Mangunkusumo Hospital, Indonesia. Patients' resuscitation endpoints data and outcome were observed during the first 120 hours of hospitalization. Cox's proportional hazard regression analysis was used to analyse the early mortality risk in subject groups achieving lactate clearance target only, ScvO2 target only, both targets, and not achieving any target in 6 hours after onset of resuscitation adjusted for number of organ dysfunction. RESULTS: subjects consisted of 268 patients. There were significant differences in the mortality risk between subjects who achieved both targets with subjects who achieved ScvO2 target only (adjusted hazard ratio [aHR] 13.47; 95% confidence interval [CI] 5.17-35.08) and subjects who not achieve any target (aHR 16.12; 95%CI 7.43-34.95). There were insignificant difference the early mortality risk between subjects who achieved both targets with subjects achieved lactate clearance target only (aHR 2.29; 95%CI 0.83-6.32). CONCLUSION: in patients with sepsis and septic shock, achievement of lactate clearance and ScvO2 targets associates with similar early mortality risk compared to achievement of lactate clearance target only. However, it associates with lower early mortality risk compared with ScvO2 target only.

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection.

Background: The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods: A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results: A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025-1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004-1.074) had an adjusted association with severe plasma leakage. Conclusions: In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection.

BACKGROUND: There are several limitations in diagnosing plasma leakage using the World Health Organization (WHO) guidelines of dengue hemorrhagic fever. We conducted a study to develop a dengue scoring system to predict pleural effusion and/or ascites using routine laboratory parameters. METHODS: A prospective observational study was carried out at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Dengue-infected adults admitted on the third febrile day from March, 2010 through August, 2015 were included in the study. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites and to convert the prediction model into a scoring system. RESULTS: A total of 172 dengue-infected adults were enrolled in the study. Of the 172 patients, 101 (58.7 %) developed pleural effusion and/or ascites. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites in dengue-infected adults. The predictors were scored based on the following calculations: hemoconcentration ≥15.1 % had a score of 1 (OR, 3.11; 95 % CI, 1.41-6.88), lowest albumin concentration at critical phase ≤3.49 mg/dL had a score of 1 (OR, 4.48; 95 % CI, 1.87-10.77), lowest platelet count ≤49,500/µL had a score of 1 (OR, 3.62; 95 % CI, 1.55-8.49), and elevated ratio of AST ≥2.51 had a score of 1 (OR 2.67; 95 % CI, 1.19-5.97). At a cut off of ≥ 2, the Dengue Score predicted pleural effusion and/or ascites diagnosis with positive predictive value of 79.21 % and negative predictive value of 74.63 %. This prediction model is suitable for calibration and good discrimination. CONCLUSIONS: We have developed a Dengue Score that could be used to identify pleural effusion and/or ascites and might be useful to stratify dengue-infected patients at risk for developing severe dengue.

Antifungal Susceptibility Testing in HIV/AIDS Patients: a Comparison Between Automated Machine and Manual Method.

AIM: to evaluate the performance of Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patients. METHODS: a comparison study to evaluate Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patient was done. Categorical agreement between manual disc diffusion and Vitek2 machine was calculated using predefined criteria. Time to susceptibility result for automated and manual methods were measured. RESULTS: there were 137 Candida isolates comprising eight Candida species with C.albicans and C. glabrata as the first (56.2%) and second (15.3%) most common species, respectively. For fluconazole drug, among the C. albicans, 2.6% was found resistant on manual disc diffusion methods and no resistant was determined by Vitek2 machine; whereas 100% C. krusei was identified as resistant on both methods. Resistant patterns for C. glabrata to fluconazole, voriconazole and amphotericin B were 52.4%, 23.8%, 23.8% vs. 9.5%, 9.5%, 4.8% respectively between manual diffusion disc methods and Vitek2 machine. Time to susceptibility result for automated methods compared to Vitex2 machine was shorter for all Candida species. CONCLUSION: there is a good categorical agreement between manual disc diffusion and Vitek2 machine, except for C. glabrata for measuring the antifungal resistant. Time to susceptibility result for automated methods is shorter for all Candida species.

Nocturnal Hypertension: Neglected Issue in Comprehensive Hypertension Management.

The body circardian rhythm affects blood pressure variability at day and night, therefore blood pressure at day and night might be different. Nocturnal hypertension is defined as increase of blood pressure >120/70mmHg at night, which is caused by disturbed circadian rhythm, and associated with higher cardiovascular and cerebrovascular events also mortality in hypertensive patients. Nocturnal hypertension and declining blood pressure pattern, can only be detected by continuous examination for 24 hours, also known as ambulatory blood pressure measurement (ABPM). Chronotherapy, has become a strategy for managing the hypertensive nocturnal patients, by taking hypertensive medication at night to obtain normal blood pressure decrease in accordance with the normal circadian rhythm and, improving blood pressure control.

HIF2-α Expression in CML Patients Receiving Hydroxyurea Prior to Imatinib That Achieved Major Molecular Response (MMR) versus in Those Not Achieving MMR.

Introduction: Currently, Imatinib (IM) which is a Tyrosine Kinase Inhibitor (TKI), is the main treatment for patients with chronic myeloid leukemia (CML). Major molecular response (MMR) is used as therapeutic response. Resistance to IM may be caused by hypoxia which is regulated by hypoxia inducible factor (HIF) 2-α. The role of HIF2-α is currently not researched extensively. This study aimed to analyse the differences in HIF-2α expression between chronic phase CML patients that achieved MMR and those that did not achieve MMR. Methods: This study used a cross-sectional method which analysed secondary data from whole blood samples in chronic phase CML patients aged 18-60 years that received hydroxyurea (HU) before IM, aged 18-60 years, received IM therapy for more than 12 months, and were willing to participate in the study. The exclusion criteria for this study were patients who were receiving IM at a dose of more than 400 mg/day. HIF-2α protein expression was examined using the enzyme-linked immunosorbent assay (ELISA) method. Differences between HIF-2α protein expression in groups that achieved MMR versus not achieving MMR was analysed using the Mann-Whitney test. Results: A total of 79 subjects were obtained. The median HIF-2α was 90.56 pg/mg protein (3.01-4628.74). There was no statistically significant difference in expression of HIF-2α in the group that reached MMR and did not reach MMR, namely 123.45 pg/mg protein and 89.25 pg/mg protein respectively (p 0.718). Conclusion: This study found no statistically significant difference between HIF-2α expression level and MMR achievement of chronic phase CML patients who received HU before IM therapy.

Antimicrobial resistance among common bacterial pathogens in Indonesia: a systematic review.

Background: The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia. Methods: We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379). Findings: Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of Klebsiella pneumoniae isolates, 18.3% of Escherichia coli isolates, 35.8% of Pseudomonas aeruginosa isolates and 70.7% of Acinetobacter baumannii isolates were carbapenem-resistant; 29.9% of Streptococcus pneumoniae isolates were penicillin-resistant; and 22.2% of Staphylococcus aureus isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant K. pneumoniae and E. coli, and penicillin-resistant S. pneumoniae increased over time. In communities, 28.3% of K. pneumoniae isolates and 15.7% of E. coli isolates were carbapenem-resistant, 23.9% of S. pneumoniae isolates were penicillin-resistant, and 11.1% of S. aureus isolates were methicillin-resistant. Data were limited for the other pathogens. Interpretation: AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions. Funding: Wellcome Africa Asia Programme Vietnam.

Diagnostic and antibiotic use practices among COVID-19 and non-COVID-19 patients in the Indonesian National Referral Hospital.

BACKGROUND: Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. METHODS: We linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used. RESULTS: Of 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; p<0.001). Cumulative incidence of having a BC taken within 28 days was higher in COVID-19 than in non-COVID-19 patients (44.7% [149/333] vs. 33.2% [6,254/18,837]; adjusted subdistribution-hazard ratio [aSHR] 1.71, 95% confidence interval [CI] 1.47-1.99, p<0.001). The median time to discontinuation of parenteral antibiotics was longer in COVID-19 than in non-COVID-19 patients (13 days vs. 8 days; aSHR 0.73, 95%Cl 0.65-0.83, p<0.001). CONCLUSIONS: Routine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.