Resuscitation of hemorrhagic shock using normal saline does not damage the glycocalyx in the immediate resuscitation phase.

OBJECTIVES: The objectives were to study the effect of aggressive resuscitation using normal saline on hemodynamics, serum atrial natriuretic peptide (ANP), syndecan-1 (marker of endothelial glycocalyx shedding), and extravascular lung water index (ELWI) following hemorrhagic shock. METHODS: Eleven male piglets (Sus scrofa) underwent blood drawing to create 20% drop in mean arterial pressure (MAP). Two-phase resuscitation was performed: Phase 1 using normal saline of an equal volume of blood drawn to create shock and Phase 2 using 40 ml/kg BW of normal saline to simulate hypervolemia and hemodilution. Heart rate, MAP, cardiac index (CI), systemic vascular resistance index, oxygen delivery (DO2), global end-diastolic volume index, ELWI, hemoglobin (Hb), lactate, ANP, and syndecan-1 at each phase and up to 60 min following Phase 2 resuscitation were recorded. RESULTS: Phase 2 resuscitation significantly decreased Hb concentration (P = 0.006), however, DO2 was maintained (P = 1.000). CI increased from shock to Phase 1 (P = 0.029) and further increase in Phase 2 resuscitation (P = 0.001). Overall, there was a transient increase of ANP following Phase 1 resuscitation, from 85.20 ± 40.86 ng/L at baseline to 106.42 ± 33.71 ng/L (P = 0.260). Serum syndecan-1 and ELWI change at all phases were not significant. CONCLUSIONS: We demonstrate compensatory protective mechanism despite overzealous fluid resuscitation. Compensatory increased CI despite decreased Hb maintained DO2. In the absence of inflammation, serum ANP did not increase significantly, no glycocalyx shedding occurred, subsequently no change in ELWI. We show that factors other than volume overload are more dominant in causing glycocalyx shedding.

Effects of α-tocopherol on hemolysis and oxidative stress markers on red blood cells in ß-thalassemia major.

BACKGROUND: The accumulation of unpaired α-globin chains in patients with ß-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with ß-thalassemia major. PURPOSE: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with ß-thalassemia major. METHODS: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions. RESULTS: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio. CONCLUSION: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in ß-thalassemia major.

Plasmodium falciparum Isolates Carrying pfk13 Polymorphisms Harbor the SVMNT Allele of pfcrt in Northwestern Indonesia.

Artemisinin-based combination therapy (ACT) is the first-line antimalarial regimen in Indonesia. Susceptibility of Plasmodium falciparum to artemisinin is falling in the Greater Mekong subregion, but it is not known whether the efficacy of current combinations is also threatened in nearby Sumatera. We evaluated the genetic loci pfcrt, pfmdr1, and pfk13, considered to be under selection by artemisinin combination therapy, among 404 P. falciparum infections identified by PCR detection in a cross-sectional survey of 3,731 residents of three regencies. The pfcrt haplotype SVMNT (codons 72 to 76) was the most prevalent and displayed significant linkage disequilibrium with the pfmdr1 haplotype YY (codons 86 and 184) (odds ratio [OR] 26.7; 95% confidence interval [CI], 5.96 to 239.4; P < 0.001). This contrasts with Mekong countries, where the CVIET haplotype of pfcrt predominates. Among 231 evaluable isolates, only 9 (3.9%) showed any evidence of nonsynonymous gene variants in the propeller domain of pfk13 The Thr474Ala variant was seen in six individuals, and Cys580Tyr was identified with low confidence in only a single isolate from an asymptomatic individual. Among a subset of 117 symptomatic P. falciparum-infected individuals randomized to receive either dihydroartemisinin-piperaquine or artemether-lumefantrine, the treatment outcome was not associated with pretreatment genotype. However, submicroscopic persistent parasites at day 28 or day 42 of follow-up were significantly more likely to harbor the pfmdr1 haplotype NF (codons 86 and 184) than were pretreatment isolates (P < 0.001 for both treatment groups). Current ACT regimens appear to be effective in Sumatera, but evidence of persistent submicroscopic infection in some patients suggests further detailed studies of drug susceptibility should be undertaken.

Recurrence of Plasmodium malariae and P. falciparum Following Treatment of Uncomplicated Malaria in North Sumatera With Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine.

BACKGROUND: We assessed the efficacy of artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria, with or without co-infecting Plasmodium spp., in Sumatera, Indonesia. METHODS: Febrile patients aged >6 months with uncomplicated P. falciparum were randomized to receive dihydroartemisinin-piperaquine or artemether-lumefantrine, plus single-dose primaquine, and were followed for 42 days. Mixed Plasmodium infections were included; P. vivax infections received 14 days of primaquine. We retrospectively restricted the analysis to cases with polymerase chain reaction (PCR)-confirmed parasitemia. Recurrent parasitemia in follow-up was identified by species-specific nested PCR. RESULTS: Of the 3731 participants screened, 302 were enrolled and randomized. In the dihydroartemisinin-piperaquine arm, P. falciparum infections were confirmed by PCR in 59 participants, with mixed infections in 23 (39.0%). In the artemether-lumefantrine arm, P. falciparum infections were confirmed by PCR in 55 participants, with mixed infections in 16 (29.0%). Both regimens were well tolerated, and symptoms improved rapidly in all treated participants. In the dihydroartemisinin-piperaquine arm, 1 P. falciparum recurrence (on day 7) and 6 P. malariae recurrences (1 had a mixed infection with P. falciparum) were identified during days 3-42 of follow-up. In the artemether-lumefantrine arm, 1 P. falciparum/P. malariae/P. vivax recurrence occurred on day 35. Submicroscopic persistence occurred during follow-up in 21 (37%) of 57 receiving dihydroartemisinin-piperaquine and 20 (39%) of 51 receiving artemether-lumefantrine. CONCLUSIONS: In Sumatera, both regimens effectively cleared initial parasitemia, but P. falciparum and P. malariae persisted in some individuals. Molecular species detection should be deployed in antimalarial efficacy trials in Indonesia. TRIAL REGISTRATION: NCT02325180.

The Association between the Level of Antithrombin III and Mortality in Children with Sepsis.

BACKGROUND: Sepsis is a significant cause of morbidity and mortality in children. The diagnosis of sepsis remains continuing to develop which determines treatment and prognostic. Antithrombin III is one of the coagulation markers to evaluate the prognosis of sepsis. AIM: To determine the association between the level of antithrombin III and mortality in children with sepsis in the Pediatric Intensive Care Unit, Haji Adam Malik General Hospital, Medan. METHODS: A cross-sectional study was conducted in Haji Adam Malik General Hospital, Medan from April until June 2015. There were 41 children with sepsis. Sepsis was diagnosed from clinical and laboratory findings. Complete blood count, antithrombin III level, C-reactive protein and procalcitonin were an indicator of unproven sepsis that performed in the laboratory. Meanwhile blood culture was performed in the microbiology laboratory. The association between the level of antithrombin III and mortality was analysed by using chi-square test. RESULTS: Of the 41 participants, the low antithrombin III level was 13 of 41 children (31.7%) meanwhile the normal antithrombin III level was 28 of 41 children (68.3%). There was 8 of 13 (42.1%) and 11 of 28 (57.9%) children in death cases of low and normal antithrombin III level, respectively. Samples with low antithrombin III level had 2.473 higher risk mortality than normal antithrombin III level (P = 0.184; 95% CI 0.641 to 9.5421; PR = 2.473). CONCLUSION: There was no statistically significant association between levels of antithrombin III and mortality in children with sepsis.

Prevalence and Knowledge of Soil-Transmitted Helminth Infections in Mandailing Natal, North Sumatera, Indonesia.

BACKGROUND: Soil-transmitted helminth (STH) infection remains of public health importance, particularly in developing countries. North Sumatra province of Indonesia has reported high prevalences of STH in many of its districts. AIM: In this study, we aimed to determine the prevalence of STH and evaluated STH knowledge and risk behaviours of school children in Mandailing Natal district. METHODS: We conducted a cross-sectional study in two primary schools in Mandailing Natal district, North Sumatera province, Indonesia. Data were collected directly from the subjects using a questionnaire after receiving consent from their parents. A stool sample was also collected to determine the STH status of each subject. Samples were then transported to the parasitology laboratory at Universitas Sumatera Utara in Medan to be analysed by a trained analyst. Kato-Katz method was used to prepare the slides (World Health Organization, 2002). The intensity of infection is classified into light, moderate and heavy infection. RESULTS: Prevalence of STH infections were 76.8% and 87.2% in Singkuand and Sikapas primary schools, respectively. The majority of infections were Ascaris lumbricoides and Trichuris trichiura at a light intensity. Only small numbers of children in the two schools used soap before eating, used soap after defecating, and wear sandal/shoes when walking outdoor. Less than 50% of children also knew the route of transmission of STH. Poorer knowledge and behaviours were shown in children from Sikapas than in Singkuang. CONCLUSION: High prevalence and poor hygiene behaviours found in this study reinforce the need to identify the correct intervention to address this STH problem in the region.

The Influence of Albumin Level in Critically Ill Children to Length of Stay and Mortality in Paediatric Intensive Care Unit.

BACKGROUND: The use of albumin in the critical care setting is a very controversial issue. Low serum albumin concentration in critical illness is associated with a poor outcome. AIM: We aimed to evaluate the influence of albumin level in critically ill children to the length of stay and mortality in the Pediatric Intensive Care Unit (PICU) Haji Adam Malik General Hospital, Medan, Indonesia. METHODS: The study used an observational method with a cross-sectional design. The population of the study was all patients with major postoperative surgery and critically ill that admitted to the PICU at Haji Adam Malik Hospital from the period of June 2008 to September 2008. The albumin level of the subjects was determined on the first day admitted. RESULTS: The group with hypoalbuminemia (< 3 g/dL) was given albumin supplementation according to a protocol in the PICU. The group with hypoalbuminemia have an average length of stay 7.6 days (9.7%) and mortality of 12 subjects (36.4%). The group with normal albumin level have 4.7 days (5.0%) and mortality 13 subjects (37.1%). There was no significant effect of albumin level to mortality. CONCLUSION: Albumin level did not affect the length of stay and mortality in PICU.

Correlation of Troponin Level (Troponin T, Troponin I) With PELOD-2 Score in Sepsis as a Predictive Factor of Mortality.

BACKGROUND: Sepsis in children with cardiovascular involvement can increase mortality. Recently, many studies have been conducted to investigate troponin as an early marker of myocardial dysfunction, associated with pediatric sepsis score. Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score is recent scoring to assess organ dysfunction in sepsis children. AIM: To determine the correlation between troponin T, troponin I with PELOD-2 score in sepsis as a predictive factor of mortality. METHODS: A prospective cohort study was conducted on sepsis children in PICU Haji Adam Malik General Hospital, Medan. Assessment of PELOD-2 score, serum troponin T, and troponin I levels performed on the first day and 48 hours after sepsis was diagnosed. Patients were observed until moved to the ward or died. RESULTS: A group of 41 subjects were recruited in this study. Troponin T level at 24 hours did not correlate with PELOD-2 scores. Troponin T level at 48 hours was positively correlated with PELOD-2 score (r = 0.771, p < 0.001) and had a significant association with the mortality rate (p < 0.001). Troponin T at 48 hours could be used as a predictive factor of mortality (AUC 86.4%, p < 0.001) with a cut-off point of 40.3 ng/mL (76% sensitivity, 75% specificity, RR 2.48). Troponin I levels at 24 and 48 hours also had strong correlation with PELOD-2 score (r = 0.326, p = 0.037; r = 0.691, p < 0.001) and could be used as a predictor of mortality in pediatric patients with sepsis (AUC 74.8%, p 0.008; AUC 92.6%, p < 0.001). The cut-off point of troponin I at 24 hours was 0.075 ng/mL (68% sensitivity, 68.8% specificity, RR 1.84) and at 48 hours was 0.125 ng/mL (80% sensitivity, 81.3% specificity, RR 3.13). CONCLUSION: Serum troponin T and troponin I levels at 48 hours have positive correlation with PELOD-2 score as a predictive factor of mortality in pediatric patients with sepsis.

Mean Blood Pressure Difference among Adolescents Based on Dyssomnia Types.

BACKGROUND: Dyssomnia is the most frequent sleep disturbance and associated with increased blood pressure. There has been no study determining the difference in mean blood pressure based on dyssomnia types among adolescents. OBJECTIVE: To determine the difference in mean blood pressure among adolescents based on dyssomnia types. METHODS: Cross-sectional study was conducted in SMP Negeri 1 Muara Batang Gadis in April 2016. Samples were students having sleep disturbance based on Sleep Disturbance Scale for Children (SDSC) questionnaire. Stature and blood pressure data were collected along with demographic data and sleep disorder questionnaire. Analyses were done with Kruskal-Wallis test and logistic regression. P - value < 0.05 was considered significant. RESULTS: Seventy-six samples were obtained with mean age 13.9 (SD 1.14) years - old. Dyssomnia proportion and hypertension were 72/76 and 20/76 respectively. Mean systolic (SBP) and diastolic blood pressure (DBP) was 111.1 (SD 16.46) mmHg and 70.3 (SD 11.98) mmHg respectively. Mean SDSC score was 49.7 (SD 8.96), and the most frequent dyssomnia type was disorders of initiating and maintaining sleep. Age and sex were not the risk factors of hypertension in dyssomnia. There was a significant difference in mean SBP (P = 0.006) and DBP (P = 0.022) based on dyssomnia types. Combination dyssomnia type had the highest mean blood pressure among dyssomnia types. CONCLUSION: There is a significant difference in mean blood pressure among adolescents based on dyssomnia types.

Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia.

Background: As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province. Methods: A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi. Results: Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%). Conclusions: Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities.