Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

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.

Prevalence and Factors Related to Hypovitaminosis D in Type 2 Diabetes Mellitus Patients with Depression.

BACKGROUND: The prevalence of hypovitaminosis D (hypoD) in patients with type 2 diabetes mellitus (T2DM) and depression has not been documented. In addition, the risk factors are unknown. This study aimed to identify the prevalence of and risk factors for hypoD in patients with T2DM who also have depression. METHODS: 118 patients with T2DM who visited the outpatient endocrinology clinics at Cipto Mangunkusumo National Hospital between December 2019-September 2022 provided the clinical and demographic data for this cross- sectional study, including body mass index, blood pressure, glycosylated haemoglobin (HbA1c), lipid profiles, therapy, gender, age, marital status, and educational background. We used The Beck Depression Inventory II (BDI II) to evaluate depression. We used enzyme-linked immunosorbent assay kit to assess the dependent variable: serum vitamin D. We characterized serum vitamin D levels into three groups (normal, 30 ng/mL; insufficient, 20-29 ng/mL; deficient, 20 ng/mL). We also used analyses of variance to examine the anthropometric, clinical, and biochemical factors between the three groups. RESULTS: 118 subjects with T2DM. Their median age was 56 years old (48, 75-60 years old), with a BDI II score of 17 (15-19), and a serum concentration of vitamin D. The D level was 18.3 ng/mL (9.17-29.46 ng/mL). Only 21.8% of patients with T2DM and depression had sufficient levels of vitamin D. We used multivariable analysis of variance model to examine the associations between age, BDI II score, HbA1c, and systolic and diastolic blood pressure with vitamin D level. Age and BDI II score both had a statistically significant effect on vitamin D levels. CONCLUSION: This cross-sectional study discovered that patients with T2DM and depression had a high prevalence (77.7%) of hypoD. Age and BDI II score both affected differences in vitamin D levels with statistical significance.

Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.

Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37-4.96) ng/mg protein in the LL-37 group and 1.11 (0.24-2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562.

Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever.

BACKGROUND: Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. METHODS: To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia. RESULTS: After a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease. CONCLUSIONS: Our results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.

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.

Supportive Psychotherapy for Healthcare Professionals in The Management of Acute Coronary Syndrome: The Use of Delphi Technique.

BACKGROUND: Supportive psychotherapy (SP) may increase the benefit of acute coronary syndrome (ACS) management, but there is no structured SP as a guideline for healthcare professionals. This study aimed to develop structured SP as a guideline for implementing psychotherapy in the management of ACS patients in intensive cardiac care unit (ICCU). METHODS:  This qualitative study used Delphi technique as a modified Delphi method to reach a consensus among experts of structured SP for healthcare professionals in the management of ACS during hospitalized in ICCU. This was developed using self-reflection, observation, and interview of SP implementation in daily psychosomatic practice, gathering literature reviews, doing focus group discussion (FGD) and interview with ACS survivors. During the Delphi rounds, we interviewed 50 informants as source people using valid questionnaires, to proceed a draft of the SP framework and the structured sessions. The SP framework draft and the structured sessions were evaluated and corrected by experts anonymously until the consensus was reached. The validity of the consensus was tested, using Likert psychometric scale to reach an agreement. Cronbach alpha test was used to assess construct validity with SPSS 20. RESULTS:  All of preparations conducted before the Delphi rounds showed that ACS patients had psychosomatic disorders during in ICCU, that required support. SP is very helpful to reduce the negative impact of this disorders.Off 50 informants answered a valid and reliable questionnaire which supports the above statement. The draft was made based on the above process. The development of SP for healthcare professionals of ACS managements was reached in a consensus of expert panelists in the second round of the Delphi with Cronbach alpha of 0.9. CONCLUSION: Supportive psychotherapy (SP) for healthcare professionals in the management of ACS in ICCU were developed and may be applied in clinical practice and research.

Blood culture utilization and epidemiology of antimicrobial-resistant bloodstream infections before and during the COVID-19 pandemic in the Indonesian national referral hospital.

BACKGROUND: There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and during the COVID-19 pandemic in the Indonesian national referral hospital. METHODS: We evaluated blood culture utilization rate, and proportion and incidence rate of AMR-BSI caused by WHO-defined priority bacteria using routine hospital databases from 2019 to 2020. A patient was classified as a COVID-19 case if their SARS-CoV-2 RT-PCR result was positive. The proportion of resistance was defined as the ratio of the number of patients having a positive blood culture for a WHO global priority resistant pathogen per the total number of patients having a positive blood culture for the given pathogen. Poisson regression models were used to assess changes in rate over time. RESULTS: Of 60,228 in-hospital patients, 8,175 had at least one blood culture taken (total 17,819 blood cultures), giving a blood culture utilization rate of 30.6 per 1,000 patient-days. A total of 1,311 patients were COVID-19 cases. Blood culture utilization rate had been increasing before and during the COVID-19 pandemic (both p < 0.001), and was higher among COVID-19 cases than non-COVID-19 cases (43.5 vs. 30.2 per 1,000 patient-days, p < 0.001). The most common pathogens identified were K. pneumoniae (23.3%), Acinetobacter spp. (13.9%) and E. coli (13.1%). The proportion of resistance for each bacterial pathogen was similar between COVID-19 and non-COVID-19 cases (all p > 0.10). Incidence rate of hospital-origin AMR-BSI increased from 130.1 cases per 100,000 patient-days in 2019 to 165.5 in 2020 (incidence rate ratio 1.016 per month, 95%CI:1.016-1.017, p < 0.001), and was not associated with COVID-19 (p = 0.96). CONCLUSIONS: In our setting, AMR-BSI incidence and etiology were similar between COVID-19 and non-COVID-19 cases. Incidence rates of hospital-origin AMR-BSI increased in 2020, which was likely due to increased blood culture utilization. We recommend increasing blood culture utilization and generating AMR surveillance reports in LMICs to inform local health care providers and policy makers.

An Extremely Rare Case of Upper Thoracic Salmonella Infection.

BACKGROUND: Vertebral osteomyelitis is rare. Finding the right etiological agent is important to administer antibiotic regimen accordingly. The occurrence of this disease in endemic countries raises the susceptibility of a more common infection such as tuberculosis and pyogenic bacteria. Salmonella spp. infection is also common in endemic countries; however, extra-intestinal manifestation is very rare. METHODS: We present an extremely rare case of salmonella vertebral osteomyelitis (SVO) in the upper thoracic vertebrae of a 64-year-old patient with history of cardiac surgery and other pre-existing comorbidities. SVO was treated by antibiotics, surgical debridement and spinal stabilization. RESULTS: Three weeks after surgery and intravenous antibiotics, the patient recovered and was discharged without fever and back pain, with excellent motoric improvement. CONCLUSION: Salmonella infection must be considered to be one of possible etiological agents in patients with suggestive spondylitis in emerging countries, especially in those with comorbidities.

The Differential Effects of Propylthiouracil and Methimazole as Graves' Disease Treatment on Vascular Atherosclerosis Markers: A Randomized Clinical Trial.

Background: Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease. Objective: This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism. Methods: This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)]. Results: By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group. Conclusion: Antithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

The Association between Peripheral Th17, Th1, IL-17, and IFN-γ Levels and TACE Response in Patients with Unresectable Hepatocellular Carcinoma with or without Cirrhosis.

BACKGROUND: Th17 cells, a subset of CD4+ T cells with the capacity to produce IL-17, were reported to have pro-tumor and anti-tumor effects. Th1 cells are known for their capacity to eliminate tumor cells by producing IFN-γ. Transarterial chemoembolization (TACE) is a treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). Therefore, this study aimed to determine the association between peripheral Th17, Th1, IL-17, and IFN-γ levels and TACE response in patients with unresectable HCC with or without cirrhosis. METHODS: a prospective cohort study was conducted in Cipto Mangunkusumo Hospital and several affiliated hospitals from June 2015 to January 2019. HCC patients with or without cirrhosis who met the inclusion criteria were included in this study. Blood samples were obtained immediately before TACE and 30 days after TACE. Th1 and Th17 cells were analyzed by flowcytometry, while IL-17 and IFN-γ were examined with ELISA method. TACE response was assessed with mRECIST. RESULTS: forty-one HCC patients were enrolled in this study. According to mRECIST, 12 patients were assessed as response group (complete and partial response) and 29 patients were assessed as nonresponse group (stable and progressive disease). Levels of Th1 and Th17 increased significantly after TACE in the response group. On the other hand, IL-17 and IFN-γ decreased after TACE in both groups, although not statistically significant. Interestingly, in the response group, a significant increase was found in the number of T cells subset showing both IFN-γ and IL-17 markers on their surfaces, i.e. CD4+/IFN-γ+/IL-17+ T cells. CONCLUSION: increased circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells were observed in HCC patients with complete or partial response to TACE.

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.

Effects of low versus standard pressure pneumoperitoneum on renal syndecan-1 shedding and VEGF receptor-2 expression in living-donor nephrectomy: a randomized controlled study.

BACKGROUND: Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation. METHODS: We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO2, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded. RESULTS: The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders. CONCLUSION: The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT:03219398, prospectively registered on July 17th, 2017.

Nonalcoholic fatty liver disease is associated with increased hemoconcentration, thrombocytopenia, and longer hospital stay in dengue-infected patients with plasma leakage.

A prominent histopathological feature of fatal dengue cases is hepatic steatosis. However, the association between hepatic steatosis and dengue severity is unknown. We conducted a study to determine the associations of nonalcoholic fatty liver disease (NAFLD) with laboratory markers of dengue severity and length of hospital stay (LOS). A retrospective study was conducted at a private hospital in Jakarta, Indonesia, from December 2011 to December 2016. Bivariate analysis was performed to analyze the associations of laboratory markers of dengue severity and LOS with the presence or absence of NAFLD in no-plasma-leakage (no leakage) and plasma-leakage (leakage) groups. There were 267 dengue-infected patients included in this study. Of these patients, 115 (43.1%) were classified as belonging to the no leakage group, and 152 (56.9%) were classified as belonging to the leakage group. Of the 115 patients belonging to the no leakage group, 53 (46.1%) did not have NAFLD, and 62 (53.9%) had NAFLD. Of the 152 patients belonging to the leakage group, 85 (55.9%) did not have NAFLD, and 67 (44.1%) had NAFLD. Leakage group patients with NAFLD experienced significantly higher hemoconcentration severity (p = 0.04), lower platelet count (p = 0.004) and higher LOS (p = 0.042) than did leakage group patients without NAFLD. The presence of NAFLD in dengue-infected patients with plasma leakage was associated with more severe hemoconcentration, thrombocytopenia and prolonged hospital stay.

Dengue score as a diagnostic predictor for pleural effusion and/or ascites: external validation and clinical application.

BACKGROUND: The Dengue Score is a model for predicting pleural effusion and/or ascites and uses the hematocrit (Hct), albumin concentration, platelet count and aspartate aminotransferase (AST) ratio as independent variables. As this metric has not been validated, we conducted a study to validate the Dengue Score and assess its clinical application. METHODS: A retrospective study was performed at a private hospital in Jakarta, Indonesia. Patients with dengue infection hospitalized from January 2011 through March 2016 were included. The Dengue Score was calculated using four parameters: Hct increase≥15.1%, serum albumin≤3.49 mg/dL, platelet count≤49,500/µL and AST ratio ≥ 2.51. Each parameter was scored as 1 if present and 0 if absent. To validate the Dengue Score, goodness-of-fit was used to assess calibration, and the area under the receiver operating characteristic curve (AROC) was used to assess discrimination. Associations between clinical parameters and Dengue Score groups were determined by bivariate analysis. RESULTS: A total of 207 patients were included in this study. The calibration of the Dengue Score was acceptable (Hosmer-Lemeshow test, p = 0.11), and the score's discriminative ability was good (AROC = 0.88 (95% CI: 0.83-0.92)). At a cutoff of ≥2, the Dengue Score had a positive predictive value (PPV) of 79.03% and a negative predictive value (NPV) of 90.36% for the diagnostic prediction of pleural effusion and/or ascites. Compared with the Dengue Score ≤ 1 group, the Dengue Score = 2 group was significantly associated with hemoconcentration> 20% (p = 0.029), severe thrombocytopenia (p = 0.029), and increased length of hospital stay (p = 0.003). Compared with the Dengue Score = 2 group, the Dengue Score ≥ 3 group was significantly associated with hemoconcentration> 20% (p = 0.001), severe thrombocytopenia (p = 0.024), severe dengue (p = 0.039), and increased length of hospital stay (p = 0.011). CONCLUSION: The Dengue Score performed well and can be used in daily practice to help clinicians identify patients who have plasma leakage associated with severe dengue.

Role of terminal warm blood cardioplegia in complex congenital heart surgery.

Introduction Myocardial protection is vital to ensure successful open heart surgery. Cardioplegic solution is one method to achieve good myocardial protection. Inevitably, ischemia-reperfusion injury occurs with aortic crossclamping. Histidine-tryptophan-ketoglutarate solution is a frequently used cardioplegia for complex congenital heart surgery. We postulated that addition of terminal warm blood cardioplegia before removal of the aortic crossclamp might improve myocardial protection. Method A randomized controlled trial was conducted on 109 cyanotic patients aged, 1 to 5 years who underwent complex biventricular repair. They were divided into a control group of 55 patients who had histidine-tryptophan-ketoglutarate only and a treatment group of 54 who had histidine-tryptophan-ketoglutarate with terminal warm blood cardioplegia. Endpoints were clinical parameters, troponin I levels, and caspase-3 as an apoptosis marker. Results The incidence of low cardiac output syndrome was 34%, with no significant difference between groups (35.2% vs. 33.3%, p = 0.84). The incidence of arrhythmias in our treatment group was lower compared to the control group (36% vs. 12%, p = 0.005). Troponin I and caspase-3 results did not show any significant differences between groups. For cases with Aristotle score ≥ 10, weak expression of caspase-3 in the treatment group post-cardiopulmonary bypass was lower compared to the control group. Conclusion For complex congenital cardiac surgery, the addition of terminal warm blood cardioplegia does not significantly improve postoperative clinical or metabolic markers.

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.

Laboratory parameters for predicting Salmonella bacteraemia: a prospective cohort study.

Blood cultures for a definitive diagnosis of typhoid fever takes time and are not routinely available. We thus investigated laboratory parameters to predict Salmonella bacteraemia. We conducted a prospective cohort study in Jakarta, Indonesia. Patients with suspected typhoid fever admitted to hospital from October 2014 to December 2016 were included. Out of 187 individuals, 27 had Salmonella typhi and 12 had S. paratyphi in blood cultures. Absolute eosinopenia, elevated aspartate aminotransferase and elevated C-reactive protein > 40 mg/L were positive predictors.

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.