Browsing by Author "University of Minnesota Medical School"
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Publication Metadata only Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry(2013-08-01) Carolyn S.P. Lam; Inder Anand; Shu Zhang; Wataru Shimizu; Calambur Narasimhan; Sang Weon Park; Cheuk Man Yu; Tachapong Ngarmukos; Razali Omar; Eugene B. Reyes; Bambang Siswanto; Lieng H. Ling; A. Mark Richards; Cardiovascular Research Institute; University of Minnesota Medical School; Fuwai Hospital; Kokuritsu Junkankibyo Senta; CARE Hospital; Korea University; Prince of Wales Hospital Hong Kong; Mahidol University; Institut Jantung Negara; Manila Doctors Hospital; Universitas IndonesiaAims: Our aim is to determine mortality and morbidity in Asian patients under clinical management for heart failure (HF). Specifically, we will define the incidence of, and risk factors for, sudden cardiac death, as well as the socio-cultural factors influencing therapeutic choices in these patients.MethodsThis is a prospective observational multinational Asian registry of 5000 patients with symptomatic HF (stage C) and LV systolic dysfunction (EF ≤ 40%) involving 44 centres across 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan and Thailand). Data collection includes demographic variables, clinical symptoms, functional status, date of HF diagnosis and prior cardiovascular investigations, clinical risk factors, lifestyle factors, socio-economic status, and survey of cultural beliefs, health practices, and attitudes towards device therapy. Centre-level characteristics (case load, referral pattern, specialization, and infrastructure) are also obtained. Patients uniformly undergo standard 12-lead ECG and transthoracic echocardiography at baseline, and are followed over 3 years for outcomes of death or hospitalization. The mode of death and cause of hospitalization are adjudicated by a central event adjudication committee using pre-specified criteria.PerspectiveBy providing prospective data regarding the demographics, risk factors, and outcomes of Asian patients under treatment for HF, the ASIAN-HF registry is expected to advance fundamental understanding of the burden and predictors of death and hospitalization among these patients. The knowledge gained will be important for guiding resource allocation and planning preventive strategies to address the unmet and growing clinical needs of patients with cardiovascular disease in Asia. © The Author 2013.Publication Metadata only Assessment of adult women with ovarian masses and treatment of epithelial ovarian cancer: Asco resource-stratified guideline(2021-01-01) Verna D. Vanderpuye; Jean Rene V. Clemenceau; Sarah Temin; Zeba Aziz; William M. Burke; Nixon Leonardo Cevallos; Linus T. Chuang; Terence J. Colgan; Marcela G. del Carmen; Keiichi Fujiwara; Elise C. Kohn; Jose Enrique Gonzáles Nogales; Thomas Okpoti Konney; Asima Mukhopadhyay; Bishnu D. Paudel; Ićo Tóth; Sarikapan Wilailak; Rahel G. Ghebre; Ramathibodi Hospital; Saitama Medical University International Medical Center; St. Paul‘s Hospital Millennium Medical College; Komfo Anokye Teaching Hospital; Bir Hospital; Massachusetts General Hospital; Hospital Angeles del Pedregal; Chittaranjan National Cancer Institute; National Cancer Institute (NCI); University of Minnesota Medical School; American Society of Clinical Oncology; Stony Brook University Hospital; LifeLabs; Mallow Flower Foundation; Sociedad Lucha Contra Cancer Ecuador; Instituto Nacional de Cancerología; Nuvance Health; Hameed Latif Hospital; Korlebu Teaching Hospital; Northern Gynaecological Oncology CentrePURPOSE To provide expert guidance to clinicians and policymakers in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. METHODS A multidisciplinary, multinational ASCO Expert Panel reviewed existing guidelines, conducted a modified ADAPTE process, and conducted a formal consensus process with additional experts. RESULTS Existing sets of guidelines from eight guideline developers were found and reviewed for resourceconstrained settings; adapted recommendations from nine guidelines form the evidence base, informing two rounds of formal consensus; and all recommendations received ≥ 75% agreement. RECOMMENDATIONS Evaluation of adult symptomatic women in all settings includes symptom assessment, family history, and ultrasound and cancer antigen 125 serum tumor marker levels where feasible. In limited and enhanced settings, additional imaging may be requested. Diagnosis, staging, and/or treatment involves surgery. Presurgical workup of every suspected ovarian cancer requires a metastatic workup. Only trained clinicians with logistical support should perform surgical staging; treatment requires histologic confirmation; surgical goal is staging disease and performing complete cytoreduction to no gross residual disease. In first-line therapy, platinum-based chemotherapy is recommended; in advanced stages, patients may receive neoadjuvant chemotherapy. After neoadjuvant chemotherapy, all patients should be evaluated for interval debulking surgery. Targeted therapy is not recommended in basic or limited settings. Specialized interventions are resourcedependent, for example, laparoscopy, fertility-sparing surgery, genetic testing, and targeted therapy. Multidisciplinary cancer care and palliative care should be offered. Additional information can be found at www.asco.org/resource-stratified-guidelines. It is ASCO's view that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.Publication Metadata only CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B(2004-12-01) Yuki Hitomi; Naoyuki Tsuchiya; Aya Kawasaki; Jun Ohashi; Takeshi Suzuki; Chieko Kyogoku; Toru Fukazawa; Sasitorn Bejrachandra; Usanee Siriboonrit; Dasnayanee Chandanayingyong; Puan Suthipinittharm; Betty P. Tsao; Hiroshi Hashimoto; Zen Ichiro Honda; Katsushi Tokunaga; University of Tokyo; University of Minnesota Medical School; Juntendo University; Mahidol University; David Geffen School of Medicine at UCLAWe previously reported association of FCGR2B-IIe232Thr with systemic lupus erythematosus (SLE) in three Asian populations. Because polymorphism of CD72, another inhibitory receptor of B cells, was associated with murine SLE, we identified human CD72 polymorphisms, tested their association with SLE and examined genetic interaction with FCGR2B in the Japanese (160 SLE, 277 controls), Thais (87 SLE, 187 controls) and Caucasians (94 families containing SLE members). Four polymorphisms and six rare variations were detected. The former constituted two major haplotypes that contained one or two repeats of 13 nucleotides in intron 8 (designated as *1 and *2, respectively). Although association with susceptibility to SLE was not detected, the *1 allele was significantly associated with nephritis among the Japanese patients (P = 0.024). RT-PCR identified a novel alternatively spliced (AS) transcript that was expressed at the protein level in COS-7 transfectants. The ratio of AS/common isoforms was strikingly increased in individuals with *2/*2 genotype when compared with *1/*1 (P = 0.000038) or *1/*2 (P = 0.0085) genotypes. Using the two Asian cohorts, significant association of FCGR2B-232Thr/Thr with SLE was observed only in the presence of CD72-*1/*1 genotype (OR 4.63, 95% Cl 1.47-14.6, P = 0.009 versus FCGR2B-232IIe/IIe plus CD72-*2/*2). Minigene assays demonstrated that the 13-nucleotide repeat and 4 bp deletion within the same haplotype of intron 8 could regulate alternative splicing. The AS isoform lacks exon 8, and is deduced to contain 49 amino acid changes in the membrane-distal portion of the extracellular domain, where considerable amino acid changes are known in CD72callele associated with murine SLE. These results indicated that the presence of CD72-*2 allele decreases risk for human SLE conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72. © Oxford University Press 2004; all rights reserved.Publication Metadata only Cognitive impairment associated with increased mortality rate in patients with heart failure: A systematic review and meta-analysis(2019-10-01) Jakrin Kewcharoen; N. Prasitlumkum; Chanavuth Kanitsoraphan; Nattawat Charoenpoonsiri; Natthapon Angsubhakorn; Prapaipan Putthapiban; Pattara Rattanawong; Chulalongkorn University; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; University of Hawaii at Manoa; University of Minnesota Medical School; Einstein Medical Center© 2019 The Authors Background: Recent systematic review and meta-analysis showed that the prevalence of cognitive impairment was significantly increased in patients with heart failure (HF) when compared to the general population. However, the effect of cognitive impairment on cardiovascular outcome in this population is still unclear. We performed a systematic review and meta-analysis to assess whether cognitive impairment associated with worse outcome in patients with HF. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to October 2018. Included studies were published cohort (prospective or retrospective) or randomized control trials that evaluate the effect of cognitive impairment mortality in HF patients. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI). Results: Eight studies were included in the analysis involving 3318 participants (951 participants had cognitive impairment). In a random-effects model, our analysis demonstrated that cognitive impairment significantly increased the risk of mortality in HF patients (pooled HR = 1.64, 95% CI = 1.42–1.88, I2 = 0.0%, p < 0.001). Conclusion: Our systematic review and meta-analysis showed that the presence of cognitive impairment is strongly associated with an increased mortality risk in the HF population. Further research is needed to explore the pathophysiology of this association.Publication Metadata only Differential contribution of FXa and thrombin to vascular inflammation in a mouse model of sickle cell disease(2014-03-13) Erica M. Sparkenbaugh; Pichika Chantrathammachart; Jacqueline Mickelson; Joanne Van Ryn; Robert P. Hebbel; Dougald M. Monroe; Nigel Mackman; Nigel S. Key; Rafal Pawlinski; The University of North Carolina at Chapel Hill; Mahidol University; Boehringer Ingelheim Pharma GmbH & Co. KG; University of Minnesota Medical SchoolActivation of coagulation and vascular inflammation are prominent features of sickle cell disease (SCD). Previously, we have shown that inhibition of tissue factor (TF) attenuates activation of coagulation and vascular inflammation in mouse models of SCD. In this study, we examined the mechanism by which coagulation proteases enhance vascular inflammation in sickle BERK mice. To specifically investigate the contribution of FXa and thrombin, mice were fed chow containing either rivaroxaban or dabigatran, respectively. In addition, we used bone marrow transplantation to generate sickle mice deficient in either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) on nonhematopoietic cells. FXa inhibition and PAR-2 deficiency in nonhematopoietic cells attenuated systemic inflammation, measured by plasma levels of interleukin-6 (IL-6). In contrast, neither thrombin inhibition nor PAR-1 deficiency in nonhematopoietic cells affected plasma levels of IL-6 in sickle mice. However, thrombin did contribute to neutrophil infiltration in the lung, independently of PAR-1 expressed by nonhematopoietic cells. Furthermore, the TF-dependent increase in plasma levels of soluble vascular cell adhesion molecule-1 in sickle mice was not mediated by FXa or thrombin. Our data indicate that TF, FXa, and thrombin differentially contribute to vascular inflammation in a mouse model of SCD. © 2014 by The American Society of Hematology.Publication Metadata only Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats(1996-01-01) Winai Wananukul; Daniel E. Keyler; Paul R. Pentel; University of Minnesota Medical School; University of Minnesota Twin Cities; Mahidol University; Hennepin County Medical CenterBackground: Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension. Methods: Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline. Results: NaHCO3briefly (5 min) reversed hypotension and QRS prolongation. CaCl2and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2group was higher than the other groups. Conclusion: The administration of CaCl2or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension.Publication Metadata only Impact of diabetes and sex in heart failure with reduced ejection fraction patients from the ASIAN-HF registry(2019-03-01) Chanchal Chandramouli; Tiew Hwa Katherine Teng; Wan Ting Tay; Jonathan Yap; Michael R. MacDonald; Jasper Tromp; Limin Yan; Bambang Siswanto; Eugenio B. Reyes; Tachapong Ngarmukos; Cheuk Man Yu; Chung Lieh Hung; Inder Anand; A. Mark Richards; Lieng Hsi Ling; Judith G. Regensteiner; Carolyn S.P. Lam; A. Mark Richards; Carolyn S.P. Lam; Inder Anand; Chung Lieh Hung; Lieng Hsi Ling; Houng Bang Liew; Calambur Narasimhan; Sang Weon Park; Eugenio Reyes; Bambang B. Siswanto; Wataru Shimizu; Shu Zhang; Manila Doctors Hospital; Care Hospital Hyderabad; Universitas Indonesia; Mackay Memorial Hospital Taiwan; University of Colorado School of Medicine; Nippon Medical School; University of Otago; National University of Singapore; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; VA Medical Center; Changi General Hospital; University of Minnesota Medical School; University of Groningen, University Medical Center Groningen; National Heart Centre, Singapore; Chinese University of Hong Kong; Queen Elizabeth Hospital; Cardiovascular Research Institute; Fuwai Cardiovascular Hospital; Sejong General Hospital© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology Aims: To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). Methods and results: Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m 2 , P interaction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33–2.57 vs. OR 1.32, 95% CI 1.11–1.56, P interaction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (P interaction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24–2.60 vs. HR 1.32, 95% CI 1.12–1.56; P interaction = 0.005). Conclusions: Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.Publication Metadata only Modulating gut microbial metabolism in heart failure: Opportunities and challenges(2021-09-01) W. H.Wilson Tang; Thanat Chaikijurajai; Cleveland Clinic Foundation; Faculty of Medicine Ramathibodi Hospital, Mahidol University; University of Minnesota Medical SchoolPublication Metadata only Myxedema Psychosis after Levothyroxine Withdrawal in Radioactive Iodine Treatment of Differentiated Thyroid Cancer: A Case Report(2021-11-08) Nutnicha Pattaravimonporn; Thanat Chaikijurajai; Wichana Chamroonrat; Chutintorn Sriphrapradang; Faculty of Medicine Ramathibodi Hospital, Mahidol University; University of Minnesota Medical SchoolNeuropsychiatric symptoms, especially acute psychosis (often referred to as myxedema madness or psychosis), are rare but possible clinical presentations of patients with hypothyroidism. A 42-year-old woman with papillary thyroid carcinoma and recent total thyroidectomy had developed flat affect, paranoid delusion, and visual and auditory hallucination during inpatient admission for elective radioactive iodine treatment. On admission, her history and physical exam did not reveal symptoms and signs of significant hypothyroidism. Other medical causes of acute psychosis were excluded, and the patient was immediately treated with thyroid hormone replacement therapy. Subsequently, her thyroid function normalized, and her psychotic symptoms gradually improved. Although there is a lack of classic signs and symptoms of hypothyroidism, myxedema madness should be recognized as one of the potentially treatable causes of acute psychosis.Publication Metadata only Nitric oxide contributes to desipramine- induced hypotension in rats(1996-01-01) P. R. Pentel; W. Wananukul; W. Scarlett; D. E. Keylerl; P. R. Pentel; D. E. Keylerl; Hennepin County Medical Center; University of Minnesota Medical School; Mahidol University; 4University of Minnesota College of Pharmacy1 Anesthetized rats received the TCA desipramine (DMI) 60 mg kg-1G-nitro-L-arginine methyl ester-(L-NAME) 15 min after DMI reversed hypotension within 5 min (P < 0.05). In contrast to its beneficial effect on blood pressure, L-NAME worsened DMI-induced prolongation of the electrocardiographic QRS interval. Dexamethasone, an inhibitor of NOS induction, did not prevent DMI-induced hypotension. 2 To study the effect of L-NAME on survival, DMI was administered to anesthetized rats as a continuous i.v. infusion until death. Despite initially improving blood pressure, L-NAME decreased the mean survival time by 33% (P < 0.01) compared to control treatment. Adminis tration of the nitric oxide (NO) donor nitroglycerine to rats during DMI infusion likewise decreased the mean survival time. 3 L-NAME partially reversed the hypotensive effect of nitroprusside in both anesthetized and awake rats. 4 These data suggest that NO production attributable to constitutive NOS (cNOS) activity aggravates the hypoten sion associated with DMI toxicity in the anesthetized rat, and contributes to the pathophysiology of this overdose. The shortened survival time produced by both increasing and decreasing NO production suggests that cNOS activity during DMI overdose is regulated and adaptive. Ongoing cNOS activity also contributed to nitroprusside-induced hypotension, and may represent a feature common to other drug-induced hypotensive states. © 1996, Sage Publications. All rights reserved.Publication Metadata only Non-Transfemoral Transcatheter Aortic Valve Replacement Approach is Associated with a Higher Risk of New-Onset Atrial Fibrillation: A Systematic Review and Meta-Analysis(2019-01-01) Natthapon Angsubhakorn; Veraprapas Kittipibul; Narut Prasitlumkum; Jakrin Kewcharoen; Wisit Cheungpasitporn; Patompong Ungprasert; University of Miami Leonard M. Miller School of Medicine; University of Hawaii at Manoa; Faculty of Medicine, Siriraj Hospital, Mahidol University; University of Minnesota Medical School; University of Mississippi Medical Center© 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ) Background: New-onset atrial fibrillation (NOAF) is a frequent arrhythmic complication following transcatheter aortic valve replacement (TAVR). Choice of access routes for TAVR could be a factor that determines the risk of NOAF although the data is still not well-characterised. We aimed to assess the association between different access routes for TAVR (transfemoral versus non-transfemoral) and the risk of NOAF. Methods: A comprehensive literature review was performed through September 2018 using EMBASE and Medline. Eligible studies must compare the incidence of NOAF in patients without pre-existing atrial fibrillation who underwent TAVR. Relative risk (RR) and 95% confidence intervals (CI) were extracted from each study and combined together using the random-effects model, generic inverse variance method of DerSimonian and Laird. Results: Seven (7) retrospective studies with 18,425 patients who underwent TAVR (12,744 with the transfemoral approach and 5,681 with the non-transfemoral approach) met the eligibility criteria. After the procedures, 2,205 (12.0%) patients developed NOAF (656 [5.1%] patients in the transfemoral group and 1,549 [27.3%] patients in the non-transfemoral group). There was a significant association between the non-transfemoral approach and an increased risk of NOAF with the pooled RR of 2.94 (95%CI, 2.53–3.41; p < 0.00001). Subgroup analysis showed the highest risk of NOAF in the transapical subgroup with the pooled RR of 3.20 (95% CI, 2.69–3.80; I2 33%). Conclusions: A significantly increased risk of NOAF following TAVR among those who underwent a non-transfemoral approach compared with transfemoral approach was observed in this meta-analysis.Publication Metadata only Pressor hyperresponsiveness in saline-infused rabbits(1984-01-01) Tetsuo Sakamaki; J. Alan Johnson; David W. Zeigler; Debra G. Koivunen; Suwan Siripaisarnpipat; Wayne L. Fowler; Charles G. Payne; University of Missouri School of Medicine; Gunma University Faculty of Medicine; University of Minnesota Medical School; Mahidol University; University of KansasConscious rabbits infused intravenously (i.v.) with isotonic saline at 1.5 to 1.8 ml/min for 24 hours had greater pressor responses to norepinephrine (NE) than did normal control rabbits. Infusion of the angiotensin II (ANGII) antagonist [Sar1, Ile8] ANGII did not decrease the exaggerated pressor responses to NE in saline-infused rabbits. Measurements of cardiac output (CO) as well as the pressor responses to NE before and after saline infusion revealed that, although saline infusion increased the CO and decreased total peripheral resistance (TPR), CO did not change during NE infusion either before or after saline infusion, but NE produced significantly greater increases in mean arterial pressure (MAP) and TPR after saline infusion than before the saline infusion. The crosscirculation of blood at 10 ml/min for 5 minutes between saline-infused donor rabbits and normal recipient rabbits resulted in pressor hyperresponsiveness to NE in the normal recipients. Similar cross-circulation experiments between pairs of normal rabbits did not alter the pressor responses to NE. These studies provided direct evidence that expansion of body fluid volumes by saline infusion results in pressor and vascular hyperresponsiveness. There was no evidence to indicate that ANG II was involved in the mechanisms producing this pressor hyperresponsiveness. Some circulating hormonal factor, however, was involved in mediating the pressor hyperresponsiveness following saline infusion. The results of this study are compatible with the concept that natriuretic hormone may play a role in promoting pressor hyperresponsiveness in saline-expanded animals. © 1984 American Heart Association, Inc.Publication Metadata only Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children(2009-03-20) Fiona E. Lovegrove; Noppadon Tangpukdee; Robert O. Opoka; Erin I. Lafferty; Nimerta Rajwans; Michael Hawkes; Srivicha Krudsood; Sornchai Looareesuwan; Chandy C. John; W. Conrad Liles; Kevin C. Kain; University Health Network University of Toronto; Mahidol University; Makerere University; University of Minnesota Medical School; University of TorontoBackground: Limited tools exist to identify which individuals infected with Plasmodium falciparum are at risk of developing serious complications such as cerebral malaria (CM). The objective of this study was to assess serum biomarkers that differentiate between CM and non-CM, with the long-term goal of developing a clinically informative prognostic test for severe malaria. Methodology/Principal Findings: Based on the hypothesis that endothelial activation and blood-brain-barrier dysfunction contribute to CM pathogenesis, we examined the endothelial regulators, angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2), in serum samples from P. falciparum-infected patients with uncomplicated malaria (UM) or CM, from two diverse populations - Thai adults and Ugandan children. Angiopoietin levels were compared to tumour necrosis factor (TNF). In both populations, ANG-1 levels were significantly decreased and ANG-2 levels were significantly increased in CM versus UM and healthy controls (p,0.001). TNF was significantly elevated in CM in the Thai adult population (p,0.001), but did not discriminate well between CM and UM in African children. Receiver operating characteristic curve analysis showed that ANG-1 and the ratio of ANG-2:ANG-1 accurately discriminated CM patients from UM in both populations. Applied as a diagnostic test, ANG-1 had a sensitivity and specificity of 100% for distinguishing CM from UM in Thai adults and 70% and 75%, respectively, for Ugandan children. Across both populations the likelihood ratio of CM given a positive test (ANG-1,15 ng/mL) was 4.1 (2.7-6.5) and the likelihood ratio of CM given a negative test was 0.29 (0.20-0.42). Moreover, low ANG-1 levels at presentation predicted subsequent mortality in children with CM (p = 0.027). Conclusions/Significance: ANG-1 and the ANG-2/1 ratio are promising clinically informative biomarkers for CM. Additional studies should address their utility as prognostic biomarkers and potential therapeutic targets in severe malaria. © 2009 Lovegrove et al.