Predictive model of return of spontaneous circulation among patients with out-of-hospital cardiac arrest in Thailand: The WATCH-CPR Score.

BACKGROUND: Out-of-hospital cardiac arrest is an emergency that requires immediate management to save lives. However, some predictive scores for the immediate outcomes of patients with out-of-hospital cardiac arrest are difficult to use in clinical practice. AIMS: This study aimed to identify predictors of sustained return of spontaneous circulation and to develop a predictive score. METHODS: This prospective observational study evaluated sustained return of spontaneous circulation among out-of-hospital cardiac arrest patients in a Thai emergency department between July 2014 and March 2018. The baseline characteristics and prehospital and hospital findings were analysed. RESULTS: Of 347 patients, 126 (36.3%) had sustained return of spontaneous circulation and 20 (5.8%) were discharged. Witnessed arrest (odds ratio = 2.9, 95% confidence interval 1.3-6.2), time from arrest to chest compression <15 min (odds ratio = 3.0, 95% confidence interval 1.3-7.0) and chest compression duration <30 min (odds ratio = 15.6, 95% confidence interval 8.7-28.0) predicted sustained return of spontaneous circulation; these were developed into the WATCH-CPR (Witnessed Arrest, Time from arrest to CHest compression-CPR duration) score. A score of ≥2 was optimal for predicting sustained return of spontaneous circulation, which provided an area under the receiver operating characteristic of 0.775 (95% confidence interval 0.724-0.825) and a sensitivity of 72.2% (95% confidence interval 63.4-79.6%) and specificity of 76.0% (95% confidence interval 69.8-81.4%). CONCLUSIONS: The factors including witnessed arrest, time from arrest to chest compression and chest compression duration were developed as the WATCH-CPR score for predicting sustained return of spontaneous circulation among patients with out-of-hospital cardiac arrest.

Predictive Factors for Death After Snake Envenomation in Myanmar.

INTRODUCTION: Factors predictive for death from snake envenomation vary between studies, possibly due to variation in host genetic factors and venom composition. This study aimed to evaluate predictive factors for death from snake envenomation in Myanmar. METHODS: A prospective study was performed among adult patients with snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to August 2016. Data including clinical variables and laboratory parameters, management, and outcomes were evaluated. Multivariate regression analysis was performed to evaluate factors predictive for death at the time of presentation to the hospital. RESULTS: Of the 246 patients with snake envenomation recruited into the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake species responsible for a bite was identified in 74 (30%) of the patients; the majority of bites were from Russell's vipers (63 patients, 85%). The independent factors predictive for death included 1) duration from bite to arrival at the hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2; P=0.04); 2) white blood cell counts >20 ×103 cells·µL-1 (OR: 8.9, 95% CI: 2.3-33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2-11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death (11/21 deaths). CONCLUSIONS: Patients who present with these independent predictive factors should be recognized and provided with early appropriate intervention to reduce the mortality rate among adults with snake envenomation in Myanmar.

Clinical and laboratory parameters associated with acute kidney injury in patients with snakebite envenomation: a prospective observational study from Myanmar.

BACKGROUND: Snakebite-related acute kidney injury (AKI) is a common community-acquired AKI in tropical countries leading to death and disability. The aims of this study were to (1) determine the occurrence of snakebite-related AKI, (2) assess factors at presentation that are associated with snakebite-related AKI, and (3) determine the outcomes of patients with snakebite-related AKI. METHODS: We conducted a prospective observational study of patients with snake envenomation at the three academic tertiary care hospitals in Yangon, Myanmar between March 2015 and June 2016. Patient data including baseline characteristics, clinical and laboratory findings, hospital management, and outcomes were recorded in a case report form. A stepwise multivariate logistic regression analysis using a backward selection method determined independent factors significantly associated with AKI. RESULTS: AKI was observed in 140 patients (54.3%), the majority of whom were AKI stage III (110 patients, 78.6%). AKI occurred at presentation and developed during hospitalization in 88 (62.9%) and 52 patients (37.1%), respectively. Twenty-seven patients died (19.3%), and 69 patients (49.3%) required dialysis. On multivariate logistic regression analysis, (1) snakebites from the Viperidae family (odds ratio [OR]: 9.65, 95% confidence interval [CI]: 2.42-38.44; p = 0.001), (2) WBC >10 × 103 cells/µL (OR: 3.55, 95% CI: 1.35-9.34; p = 0.010), (3) overt disseminated intravascular coagulation (OR: 2.23, 95% CI: 1.02-4.89; p = 0.045), (4) serum creatine kinase >500 IU/L (OR: 4.06, 95% CI: 1.71-9.63; p = 0.001), (5) serum sodium <135 mmol/L (OR: 4.37, 95% CI: 2.04-9.38; p < 0.001), (6) presence of microscopic hematuria (OR: 3.60, 95% CI: 1.45-8.91; p = 0.006), and (7) duration from snakebite to receiving antivenom ≥2 h (OR: 3.73, 95% CI: 1.48-9.37; p = 0.005) were independently associated with AKI. Patients bitten by Viperidae with normal renal function who had serum sodium <135 mmol/L had a significantly higher urine sodium-to-creatinine ratio than those with serum sodium ≥135 mmol/L (p < 0.001). CONCLUSIONS: Identifying factors associated with snakebite-related AKI might help clinicians to be aware of snakebite patients who are at risk of AKI, particularly patients who demonstrate renal tubular dysfunction after Viperidae bites.

Diagnostic accuracy of peripheral venous lactate and the 2009 WHO warning signs for identifying severe dengue in Thai adults: a prospective observational study.

BACKGROUND: Dengue is the most common mosquito-borne viral disease in humans. However, the sensitivities of warning signs (WSs) for identifying severe dengue in adults are low, and the utility of lactate levels for identifying severe dengue in adults has not been verified. Therefore, we aimed to evaluate the diagnostic accuracy of using peripheral venous lactate levels (PVL), as well as WSs established by the World Health Organization, for identifying severe dengue. METHODS: We prospectively evaluated individuals hospitalized for dengue who were admitted to the Hospital for Tropical Diseases in Thailand between May 2013 and January 2015. Blood samples to evaluate PVL levels were collected at admission and every 24 h until the patient exhibited a body temperature of <37.8 °C for at least 24 h. Data were recorded on a pre-defined case report form, including baseline characteristics, clinical parameters, and laboratory findings. RESULTS: Among 125 patients with confirmed dengue, 105 (84.0%) patients had non-severe dengue, and 20 (16.0%) patients had severe dengue. The presence of clinical fluid accumulation as a WS provided high sensitivity (75.0%, 95% confidence interval [CI]: 50.9-91.3%) and specificity (90.5%, 95% CI: 83.2-95.3%). The PVL level at admission was used to evaluate its diagnostic value, and receiver operating characteristic curve analysis revealed an area under the curve of 0.84 for identifying severe dengue. At the optimal cutoff value (PVL: 2.5 mmol/L), the sensitivity and specificity were 65.0% (95% CI: 40.8-84.6%) and 96.2% (95% CI: 90.5-99.0%), respectively. A combined biomarker comprising clinical fluid accumulation and/or PVL of ≥2.5 mmol/L provided the maximum diagnostic accuracy for identifying severe dengue, with a sensitivity of 90.0% (95% CI: 68.3-98.8%) and a specificity of 87.6% (95% CI: 79.8-93.2%). CONCLUSIONS: Clinical fluid accumulation and/or PVL may be used as a diagnostic biomarker of severe dengue among adults. This biomarker may facilitate early recognition and timely treatment of patients with severe dengue, which may reduce dengue-related mortality and hospital burden.

Identification of clinical factors associated with severe dengue among Thai adults: a prospective study.

BACKGROUND: Dengue is the most common mosquito-borne viral disease in humans. Recently, there has been an epidemic shift of dengue from mainly affecting children to affecting more adults with increased severity. However, clinical factors associated with severe dengue in adults have varied widely between studies. We aimed to identify the clinical factors associated with the development of severe dengue according to the World Health Organization (WHO)'s 2009 definition. METHODS: We conducted a prospective study of adults with dengue admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, from October 2012 to December 2014. Univariate and stepwise multivariate logistic regression analyses were performed. RESULTS: Of the 153 hospitalized patients with confirmed dengue viral infections, 132 (86.3 %) patients had non-severe dengue including dengue without warning signs (7 patients, 5.3 %) and dengue with warning signs (125, 94.7 %). The rest (21, 13.7 %) had severe dengue including severe plasma leakage (16, 76.2 %), severe organ involvement (16, 76.2 %), and severe clinical bleeding (8, 38.1 %). Using stepwise multivariate logistic regression, clinical factors identified as independently associated with the development of severe dengue were: (1) being >40 years old (odds ratio [OR]: 5.215, 95 % confidence interval [CI]: 1.538-17.689), (2) having persistent vomiting (OR: 4.817, CI: 1.375-16.873), (3) having >300 cells per µL of absolute atypical lymphocytes (OR: 3.163, CI: 1.017-9.834), and (4) having lactate levels ≥2.0 mmol/L (OR: 7.340, CI: 2.334-23.087). In addition, increases in lactate and absolute atypical lymphocyte levels corresponded with severe dengue (p < 0.05). CONCLUSIONS: Our study identified several clinical factors independently associated with the development of severe dengue among hospitalized adults with dengue. This can aid in the early recognition and prompt management of at-risk patients to reduce morbidity and mortality.

Downregulation of plasma miR-451 and miR-16 in Plasmodium vivax infection.

Malaria is a common parasitic disease in tropical countries, causing one to two million deaths every year. To establish the new biomarker, we analyzed plasma miRNAs obtained from 19 malaria patients and 19 normal subjects, using reverse transcription-based quantitative polymerase chain reaction (RT-qPCR). The average levels of plasma miR-451 and miR-16 were significantly lower in malaria patients, (8.9-fold; p <0.001 and 10.4-fold; p = 0.01, respectively). The levels of other abundant miRNAs in plasma (miR-223, miR-226-3p) did not change significantly in malaria patients. Our data suggest that plasma miR-451 and miR-16 are relevant biomarkers for malaria infection.

Factors associated with severe clinical manifestation of dengue among adults in Thailand.

A retrospective study was conducted by reviewing medical records of 323 adult patients hospitalized with dengue infection at the Hospital for Tropical Diseases, Bangkok, Thailand between 2006 and 2010 in order to determine factors associated with severe clinical manifestations of dengue. Of 323 patients, 95 (29.4%) had dengue fever (DF) and 228 (70.6%) had DHF, which were categorized as grade I (67 patients, 29.4%), grade II (62 patients, 27.2%), grade III (95 patients, 41.7%) and grade IV (4 patients, 1.8%) following 1997 WHO definitions. Using the revised 2009 WHO definitions, 233 patients (72.1%) had non-severe dengue infection and 90 patients (27.9%) had severe dengue infection. Of the 233 patients with non-severe dengue infection, 193 (82.8%) were classified as having non-severe dengue infection with warning signs and 40 (17.2%) were classified as having non-severe dengue infection without warning signs. Using stepwise multivariate logistic regression analysis, having a hematocrit >2% above the reference range [odds ratio (OR) 3.235; 95% confidence interval (CI) 1.807-5.793] or having an alanine aminotransferase level >120 IU/l (OR 1.896; 95% CI 1.018-3.531) were associated with having DHF grades II-IV, whereas female gender (OR 2.042; 95% CI 1.143-3.648) or having a mean arterial pressure <80 mmHg (OR 2.275; 95% CI 1.302-3.975) were associated with severe dengue. These findings may help clinicians to determine patients at risk for severe manifestations of dengue infection, which could lead to proper management of these cases.

Secondary dengue serotype 1 infection causing dengue shock syndrome with rhombencephalitis and bleeding associated with refractory thrombocytopenia: A case report.

Background: Dengue has a wide spectrum of manifestations, from an asymptomatic condition to dengue shock syndrome. Extensive plasma leakage, severe bleeding, or both, could lead to dengue shock syndrome, a common cause of death in dengue-infected patients. Thrombocytopenia is a common laboratory finding in dengue, which correlates with the disease severity and rapidly resolves during the recovery phase. Therefore, refractory thrombocytopenia is rare in patients with dengue. Rhombencephalitis is an inflammatory disease affecting the hindbrain, rarely associated with dengue. We report the second case of dengue-associated rhombencephalitis, wherein the patient developed dengue shock syndrome and severe bleeding associated with refractory thrombocytopenia. Case report: A 47-year-old Thai female with secondary dengue serotype 1 infection developed dengue shock syndrome with rhombencephalitis, manifested as altered sensorium and status epilepticus in the critical phase. Cerebrospinal fluid analysis showed pleocytosis with predominantly mononuclear cells and high protein levels. Magnetic resonance imaging of the brain showed multifocal brain signal abnormalities involving the medulla oblongata, pons, midbrain, bilateral hippocampi, thalami, posterior limb of internal capsules, external capsules, and deep hemispheric white matter. The patient had partial neurological recovery following rhombencephalitis for one month. During the recovery phase, severe bleeding with refractory thrombocytopenia and acute kidney injury were observed. Methylprednisolone with eltrombopag was administered, which resulted in an increased the platelet count, cessation of bleeding and recovery of kidney function within 4 days. Conclusions: Dengue is a potential cause of rhombencephalitis. Dengue-associated rhombencephalitis develops during the critical phase, with only partial neurological recovery. However, severe bleeding and refractory thrombocytopenia were also observed during the recovery phase. Methylprednisolone with a thrombopoietin receptor agonist could be an effective treatment for increasing platelet count and stopping bleeding in dengue.

Effectiveness of fixed-dose combination stavudine, lamivudine and nevirapine (GPO-VIR) for treatment of naïve HIV patients in Thailand: a 3-year follow-up.

Generic fixed dose combination stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), named GPO-VIR is recommended in the HIV treatment guidelines for Thailand. The long term effectiveness and adverse effects of this drug combination for the treatment of HIV were evaluated in an ambispective study at Bamrasnaradura Infectious Diseases Institute, Nonthaburi Province, Thailand from March 2002 to January 2006. A total of 152 adult treatment naive HIV patients who had received at least 12 months of GPO-VIR were enrolled. The median (IQR) CD4 cell count increased from 23 (8-94) cells/microl at baseline to 126 (38-180), 136 (98-189), 199 (141-255) and 334 (243-414) cells/microl at 3, 6, 12 and 24 months (p < 0.001), respectively. The median (IQR) percentage of body weights increased from baseline by 3.0% (0.3-6.3), 6.2% (2.2-9.3), 7.3% (3.9-10.9) and 8.1% (3.4-11.9) at 3, 6, 12 and 24 months, respectively and then remained at a plateau until the end of the 3-year study. The occurrence of new opportunistic infections decreased significantly (p < 0.001) with GPO-VIR treatment. Drug resistance occurred in 5 cases (3.3%) with a median (IQR) time of 18.0 (16.5-32.5) months to occurrence. Adverse effects included hypercholesterolemia (43.2%), lipodystrophy (35.5%), hypertriglyceridemia (25%), hypertension (13.1%), peripheral neuropathy (11.9%), hyperlactatemia (2.6%) and lactic acidosis (1.3%). Thirty-six patients (27%) switched from GPO-VIR to other anti-retroviral drugs regimens due to lipodystrophy. This study showed GPO-VIR had clinical and immunological benefits, but one-third of patients had adverse effects.

Evaluation of Hematocrit in Adults with Dengue by a Laboratory Information System.

The implementation of a laboratory information system (LIS) at the Hospital for Tropical Diseases in Thailand provides valuable medical resources, particularly for dengue. Hematocrit (Hct), which is often derived from hemoglobin (Hgb), is important in the diagnosis and management of dengue. This study aimed to evaluate the Hct value obtained from the LIS automated analyzer. We prospectively enrolled 163 hospitalized adults with dengue, for whom 1,141 real-time complete blood count (CBC) results were obtained via a hematology analyzer and updated in the LIS database. The median (interquartile range (IQR)) duration of analytic turnaround times (TATs) was 40.0 (30.0-53.0) minutes. Linear regression analysis indicated a significant relationship between Hgb and Hct with a coefficient of determination (Pearson's R 2) of 0.92 at red blood cell distribution width (RDW) ≤18, but Pearson's R 2 decreased to 0.78 at RDW >18. The Hct calculated from the three-fold conversion method and from the analyzer had a Pearson's R 2 of 0.92. At Hgb <12 g/dl and ≥16 g/dl, a greater difference between the two Hct values was observed, with median (IQR) differences of -0.8% (-1.9%-0.2%) and 0.8% (-0.1%-1.7%), respectively (P value <0.05). In conclusion, the Hgb and Hct of patients with dengue were highly correlated at RDW ≤18. The Hct calculated from the three-fold conversion method and from the analyzer had an excellent relationship, except when the Hgb was <12 g/dl or ≥16 g/dl. Apart from routine CBC evaluation, the LIS could help for accurate data collection in clinical research and development.

Particulate Matter 2.5 and Hematological Disorders From Dust to Diseases: A Systematic Review of Available Evidence.

Particulate matter 2.5 (PM2.5) in the air enters the human body by diffusion into the blood. Therefore, hematological abnormalities might occur because of these toxic particles, but few studies on this issue have been reported. According to Cochrane guidance, we performed a systematic review on the relationship between exposure to PM2.5 and the risk of hematological disorders. Ten articles were included in this review. Anemia was found among children and elderly populations with 2- to 5-year PM2.5 exposure. Young children from mothers exposed to air pollution during pregnancy had a higher incidence of leukemia similar to the elderly. Supporting these data, outdoor workers also showed abnormal epigenetic modifications after exposure to very high PM2.5 levels. Adults living in high PM2.5 areas for 2 years were more likely to develop thrombocytosis. Finally, elderly populations with 7- to 8-year PM2.5 exposure showed increased risks of venous thromboembolism. In conclusion, the associations between PM2.5 and hematological aberrations among high-risk people with long-term exposure were reported.

Predictors of plasma leakage among dengue patients in Thailand: A plasma-leak score analysis.

Delayed plasma leakage recognition could lead to improper fluid administration resulting in dengue shock syndrome, subsequently, multi-organ failure, and death. This prospective observational study was conducted in Bangkok, Thailand, between March 2018 and February 2020 to determine predictors of plasma leakage and develop a plasma leakage predictive score among dengue patients aged ≥15 years. Of 667 confirmed dengue patients, 318 (47.7%) developed plasma leakage, and 349 (52.3%) had no plasma leakage. Multivariate analysis showed three independent factors associated with plasma leakage, including body mass index ≥25.0 kg/m2 (odds ratio [OR] = 1.784; 95% confidence interval [CI] = 1.040-3.057; P = 0.035), platelet count <100,000/mm3 on fever days 3 to 4 (OR = 2.151; 95% CI = 1.269-3.647; P = 0.004), and aspartate aminotransferase or alanine aminotransferase ≥100 U/l on fever days 3 to 4 (OR = 2.189; 95% CI = 1.231-3.891; P = 0.008). Because these three parameters had evidence of equality, each independent factor was weighted to give a score of 1 with a total plasma-leak score of 3. Higher scores were associated with increased plasma leakage occurrence, with ORs of 2.017 (95% CI = 1.052-3.869; P = 0.035) for score 1, 6.158 (95% CI = 2.914-13.015; P <0.001) for score 2, and 6.300 (95% CI = 2.419-16.407; P <0.001) for score 3. The area under the receiver operating characteristics curves for predicting plasma leakage was good (0.677 [95% CI = 0.616-0.739]). Patients with a plasma-leak score ≥1 had high sensitivity (88.8%), and those with a plasma-leak score of 3 had high specificity (93.4%) for plasma leakage occurrence. This simple and easily accessible clinical score might help physicians provide early and timely appropriate clinical dengue management in endemic areas.

Tocilizumab for treating severe COVID-19 pneumonia refractory to combined hydroxychloroquine, lopinavir plus ritonavir, and favipiravir: A case series.

Three patients diagnosed with severe COVID-19 pneumonia received treatment with hydroxychloroquine combined with lopinavir, ritonavir, and favipiravir. Two patients diagnosed early, received tocilizumab when the pneumonia became severe and survived. The thrid patient was diagnosed late and received tocilizumab when the disease progressed to acute respiratory distress syndrome, and died.

Association of Body Dysmorphic Disorder with Leptin Levels in Patients with Normal Weight Undergoing Liposuction: A Matched Case Study.

BACKGROUND: Liposuction is the most common aesthetic surgical procedure performed globally. Some of the patients with normal weight who seek liposuction may suffer from body dysmorphic disorder (BDD). Leptin, which is mainly produced by adipose tissue, may be associated with this condition. The aim of this study was to determine the prevalence of BDD and leptin levels in patients with normal weight seeking liposuction. METHODS: Thirty-two nonobese women who sought liposuction were matched with 32 healthy volunteers by age and body mass index. Blood biochemistry, leptin levels, and BDD-Yale-Brown Obsessive-Compulsive Scale (BDD-YBOCS) questionnaires were evaluated and compared between the groups. RESULTS: Patients who underwent liposuction had significantly higher median (interquartile range) of total BDD-YBOCS scores than healthy volunteers [25 (22-27) versus 12 (8-20); P < 0.001]. Overall, 28 (87.5%) patients had total BDD-YBOCS scores of >20, whereas 10 (31.5%) volunteers had scores of >20. Patients with total BDD-YBOCS scores of >20 had significantly lower levels of serum leptin [12.43 (7.15-16.98) ng/ml versus 15.57 (9.59-22.28) ng/ml; P = 0.043]. CONCLUSIONS: Patients who underwent liposuction had a significantly higher total score of BDD-YBOCS than healthy volunteers matched by sex, age, and body mass index. Subjects with higher BDD-YBOCS scores had significantly lower serum leptin levels.

Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study.

BACKGROUND: Currently, there are no biomarkers that can predict the incidence of dengue shock and/or organ failure, although the early identification of risk factors is important in determining appropriate management to reduce mortality. Therefore, we sought to determine the factors associated with dengue shock and/or organ failure and to evaluate the prognostic value of serum procalcitonin (PCT) and peripheral venous lactate (PVL) levels as biomarkers of dengue shock and/or organ failure. METHODOLOGY/PRINCIPAL FINDINGS: A prospective observational study was conducted among adults hospitalized for confirmed viral dengue infection at the Hospital for Tropical Diseases in Bangkok, Thailand between October 2013 and July 2015. Data, including baseline characteristics, clinical parameters, laboratory findings, serum PCT and PVL levels, management, and outcomes, were recorded on pre-defined case report forms. Of 160 patients with dengue, 128 (80.0%) patients had dengue without shock or organ failure, whereas 32 (20.0%) patients developed dengue with shock and/or organ failure. Using a stepwise multivariate logistic regression analysis, PCT ≥0.7 ng/mL (odds ratio [OR]: 4.80; 95% confidence interval [CI]: 1.60-14.45; p = 0.005) and PVL ≥2.5 mmol/L (OR: 27.99, 95% CI: 8.47-92.53; p <0.001) were independently associated with dengue shock and/or organ failure. A combination of PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L provided good prognostic value for predicting dengue shock and/or organ failure, with an area under the receiver operating characteristics curve of 0.83 (95% CI: 0.74-0.92), a sensitivity of 81.2% (95% CI: 63.6-92.8%), and a specificity of 84.4% (95% CI: 76.9-90.2%). Dengue shock patients with non-clearance of PCT and PVL expired during hospitalization. CONCLUSIONS/SIGNIFICANCE: PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L were independently associated with dengue shock and/or organ failure. The combination of PCT and PVL levels could be used as prognostic biomarkers for the prediction of dengue shock and/or organ failure.

Dynamic Measurement of Hemodynamic Parameters and Cardiac Preload in Adults with Dengue: A Prospective Observational Study.

Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC) parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5%) experienced dengue shock and 145 (89.5%) did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045) and the pulse pressure was significantly lower between days 4 and 7 (P<0.05). The stroke volume index and cardiac index were significantly decreased between days 4 and 15 and between days 5 and 8 after fever onset (P<0.05), respectively. A significant proportion of patients with dengue shock had an IVC diameter <1.5 cm and IVC collapsibility index >50% between days 4 and 5 (P<0.05). Hypovolemic shock was observed in 9 (52.9%) patients and cardiogenic shock in 8 (47.1%), with a median (interquartile range) time to shock onset of 6.0 (5.0-6.5) days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock.

Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2.

BACKGROUND: In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. METHODS AND FINDINGS: We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai-Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 x 10(11) (95% confidence interval [CI] 5.8 x 10(11) to 8.5 x 10(11)) parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 x 10(12), 95% CI 1.3 x 10(12) to 2.3 x 10(12)) than in patients hospitalised without signs of severity (geometric mean 2.8 x 10(11), 95% CI 2.3 x 10(11) to 3.5 x 10(11); p < 0.001). Parasite burden was highest in patients who died (geometric mean 3.4 x 10(12), 95% CI 1.9 x 10(12) to 6.3 x 10(12); p = 0.03). The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony-but in severe malaria is unrelated to stage of parasite development. CONCLUSION: Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria. Severe malaria results from extensive sequestration of parasitised erythrocytes.

Stage-dependent production and release of histidine-rich protein 2 by Plasmodium falciparum.

Because of their sequestration in the microcirculation, the pathogenic late stages of Plasmodium falciparum are under-represented in peripheral blood samples from patients with falciparum malaria. Excreted products of the parasite might help to estimate this sequestered biomass. We quantified the stage-dependent production and release per parasite of P. falciparum histidine-rich protein 2 (PfHRP2) with the objective of measuring the sequestered biomass. A simple method to relate parasite stage to parasite age was developed to facilitate this. In four isolates of P. falciparum, the median (range) PfHRP2 content was 2.0fg (0.5-4.3fg) for a young ring stage infected erythrocyte, and 5.4fg (2.1-10.2fg) for the schizont stage. The amount of PfHRP2 in the parasitized erythrocyte increased most during development to the mature trophozoite stage. The median (range) amount of PfHRP2 secreted per parasite per entire erythrocytic cycle was 5.2fg (1.1-13.0fg). A median of 89% of the total PfHRP2 was excreted at the moment of schizont rupture. This assessment of the stage-dependent release of PfHRP2 is an essential prerequisite for future studies aimed at estimating the total patient parasite mass from the peripheral blood PfHRP2 concentration.

Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary Tuberculosis at the Central Chest Institute of Thailand.

There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case-control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86-200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52-6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64-36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89-7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06-7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future.

Acute Renal Failure in Patients with Severe Falciparum Malaria: Using the WHO 2006 and RIFLE Criteria.

There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF) in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients). The requirement for RRT was 45.2% (52 patients) and the in-hospital mortality was 31.9% (36 patients). Using the RIFLE criteria, 73.9% (190 patients) had acute kidney injury (AKI). The requirement for RRT was 11.6% (5 patients) in patients with RIFLE-I and 44.9% (48 patients) in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P < 0.05) and the in-hospital mortality (P < 0.05) were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.