Soluble ST2 Testing: A Promising Biomarker in the Management of Heart Failure / Teste com ST2 Solúvel: Um Biomarcador Promissor no Tratamento da Insuficiência Cardíaca

Abstract ST2 is a member of the interleukin-1 receptor family biomarker and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in both chronic and acute heart failure. It is a new biomarker that meets all required criteria for a useful biomarker. Of note, it adds information to natriuretic peptides (NPs) and some studies have shown it is even superior in terms of risk stratification. Since the introduction of NPs, this has been the most promising biomarker in the field of heart failure and might be particularly useful as therapy guide.

Resumo ST2 é um biomarcador pertencente à família dos receptores de interleucina-1 e concentrações do ST2 solúvel refletem fibrose e estresse cardiovascular. Estudos recentes demonstram que o ST2 solúvel é um forte preditor de desfechos cardiovasculares em pacientes com insuficiência cardíaca crônica e aguda. Trata-se de um novo biomarcador que preenche critérios necessários para uso na prática clínica. Ele acrescenta informação aos peptídeos natriuréticos (PNs) e em alguns estudos tem sido até superior a estes em relação à estratificação de risco. Desde a introdução dos PNs, este é o biomarcador mais promissor na área de insuficiência cardíaca e pode vir a ser particularmente útil para guiar a terapia.

Role of Soluble ST2 as a Prognostic Marker in Patients with Acute Heart Failure and Renal Insufficiency

This study sought to assess the relationship between serum concentrations of the soluble ST2 (sST2) and B-type natriuretic peptide (BNP) and investigate the role of sST2 as a prognosticator in patients hospitalized with acute heart failure (HF) and renal insufficiency. sST2 was measured at admission and discharge in 66 patients hospitalized with acute decompensated HF and renal insufficiency (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2) using a high sensitivity immunoassay. BNP was sampled at the same time and compared to sST2. Demographical, biochemical, and echocardiographic data were also obtained during hospitalization.There were positive correlations between sST2 and BNP levels at admission (r = 0.330, P = 0.007) and at discharge (r = 0.320, P = 0.009) in overall patients. However, there was no correlation between them at each timepoint in patients with severe renal insufficiency (eGFR < 30 mL/min/1.73 m2, n = 17). sST2 level was not changed with the degree of renal function, even though BNP level was much higher in patients with severe renal insufficiency. During 3 month follow-up, 9 (13.6%) died and 16 (24.2%) were readmitted due to HF aggravation.On multivariate analysis, sST2 at discharge was independently associated with death or HF readmission during 3 months after discharge (hazard ratio, 1.038; 95% confidence interval, 1.011-1.066, P = 0.006). In conclusion, sST2 is not affected by renal function compared with BNP in acute HF patients. The measurement of predischarge sST2 can be helpful in predicting short-term outcomes in acute decompensated HF patients with renal insufficiency.

Síndrome de carcinoma basocelular nevoide con agenesia de cuerpo calloso, mutación en PTCH1 y ausencia de carcinoma basocelular

El síndrome del carcinoma basocelular nevoide (SCBCN) o de Gorlin-Goltz es un raro desorden autosómico dominante con un amplio espectro de manifestaciones clínicas. El signo cardinal es la presencia de múltiples carcinomas basocelulares (CBCs) y su ausencia demora el diagnóstico. Presentamos un adolescente de 14 años con diagnóstico de SCBCN por la presencia de queratoquistes odontogénicos, hiper­telorismo, macrocefalia y agenesia del cuerpo calloso pero sin lesiones cutáneas. La madre, de 43 años, tiene diagnóstico de SCBCN y no presenta CBCs. Para completar el estudio se realizó secuenciación bidireccional y Multiplex Ligation dependent Probe Amplification (MLPA) en sangre periférica para buscar mutaciones en PTCH1, principal gen responsable del síndrome. Se encontró una mutación germinal novel en el paciente y la madre: una duplicación de 25 pb en el exón 10 (c.1375dupl25bp). El análisis bioinformático predijo un corrimiento del marco de lectura y un codón stop prematuro, que produciría una proteína trunca más corta que lo normal. Nuestros resultados sugieren que el estudio clínico y genealógico completo con análisis genético es fundamental para la detección temprana de casos como el presente.

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin-Goltz syndrome is a rare autosomal dominant disorder, mainly due to PTCH1 gene mutations, that comprises a broad spectrum of clinical manifestations. The presence of multiple basal cell carcinomas (BCCs) is a cardinal sign in NBCCS, therefore cases in which BCCs are absent entails a delay in the diagnosis.We present a 14 years old boy with a clinical diagnosis of NBCCS by the presence of odontogenic cysts, hypertelorism, macrocephaly, and corpus callosum agenesia, but with absence of skin lesions. His 43 years old mother has NBCCS diagnosis and no history of BCCs. For a deeper study, PTCH1 mutation screening from peripheral blood samples were performed by both bidirectional sequencing and multiplex ligation dependent probe amplification (MLPA) techniques. The proband and his mother carry 25 pb duplication in exon 10 (c.1375dupl25bp) that causes a reading frameshift with a premature stop codon. Bioinformatics analysis predicted that this mutation results in a truncated protein shorter than normal. Our results suggest that complete clinical and genealogical studies accompanied by genetic analysis are essential in the early detection of the NBCCS cases such the one presented here.

Are Soluble ST2 Levels in the Picogram or Nanogram Range in Serum of Healthy Subjects/Disease Patients?

No abstract available.

Biomarcadores pronósticos de gravedad del dengue / Biomarkers for the prognosis of severe dengue

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Introduction: There are very few strategies for the early detection of the patients who might develop the severe form of the illness. Objective: To evaluate the utility of serum levels of some immune response mediators as early biomarkers for the severe dengue prognosis during the early phase of the illness. Materials and methods: Using a case-control design nested in a multicenter cohort from the AEDES network (a Colombian multicenter study), we compared TNF a, ST2, TRAIL and IDO levels in samples which were obtained during the early phase of the illness. Results: ST2, TRAIL and TNF a levels were higher in severe dengue patients compared with uncomplicated patients (p<0.0001), as follows: OR=24.8, CI95%= 6.1- 98.0; OR=18.0, CI95%= 4.6-69.1; OR=NC, CI95%= NC, respectively. We did not find statistically significant differences between IDO levels in severe dengue and uncomplicated dengue (p=1.000, OR=1.0, CI95%= 0.2-6.1). Conclusions: In the early phase of the dengue infection (96 hours), ST2, TRAIL and TNF a quantifications could contribute to the prediction of complications of the illness.

Serum Level of Interleukin-33 and Soluble ST2 and Their Association with Disease Activity in Patients with Behcet's Disease

Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48+/-175.04 pg/mL in BD and 224.23+/-56.64 pg/mL in normal controls [P=0.048], sST2: 99.01+/-15.92 pg/mL in BD and 23.56+/-3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.

Relationship between soluble leptin receptor, leptin, lipid profiles and anthropometric parameters in overweight and obese Thai subjects.

Median, range and 95% confidence interval (CI) for median of age, anthropometric variables, soluble leptin receptor, serum leptin and lipid profile levels of 48 overweight (Body mass index (BMI) = 25.00-29.99 kg/m2) and obese (BMI > or = 30. 00 kg/m2) Thai males and 166 overweight and obese Thai females, compared with 26 males and 81 females in a control group (BMI = 18.50-24.99 kg/m2), were determined The study subjects were persons who turned up regularly for physical check-ups at the Out-patient Department, General Practice Section, Ratchawithi Hospital, Bangkok, aged between 18-60 years. Serum leptin, triglyceride and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios (LDL-C/ HDL-C ratio) were significantly higher in the overweight and obese males and females. Soluble leptin receptor and HDL-C were significantly lower in the overweight and obese males and females. Cholesterol and LDL-C were significantly higher in the overweight and obese females, but there was no significant difference in the overweight and obese males when compared with the control males. Low soluble leptin receptor levels were found in 38.1% (8/21) of the overweight and obese males, while 31.5% (29/92) were found in the overweight and obese females. Elevated leptin levels were found in 66.7% (32/48) and 89.8% (149/166) of the overweight and obese males and females, respectively. Both low soluble leptin receptor levels and elevated leptin levels were found in 9.5% (2/21) and 29.4% (27/92) of the overweight and obese males and females, respectively. A significant positive correlation was found between soluble leptin receptor and cholesterol, and between weight, BMI, waist, hip and HDL-C, with leptin. Serum soluble leptin receptor levels were significantly negatively correlated with leptin and BMI. The results can elucidate the causes and consequences of obesity, and are expected to aid the provision of care for overweight and obese Thai people.