Prognostic Utility of Biomarkers in Predicting of One-Year Outcomes in Patients with Aortic Stenosis Treated with Transcatheter or Surgical Aortic Valve Implantation

Objectives

The aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE).

Background

There is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available.

Methods

The multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0%) allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29), or SAVR with the Edwards Perimount bioprosthesis (n = 13). Standardized endpoints were prospectively followed during the 12-month follow-up.

Results

The clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis) = 0.872 for TAVI group, resp. 0.765 (p<0.05) for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1), ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750–0.948; p<0.05 for all). The addition of MDA to a currently used clinical model (EuroSCORE) significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0–365 days) by the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) (p<0.05).Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up.

Conclusion

We identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical “TAVIscore” would be highly appreciated. Such dedicated scoring system would enable further testing of adjunctive value of various biomarkers.     

The Prognostic Value of Plasma Galectin-3 in Chronic Heart Failure Patients Is Maintained when Treated with Mineralocorticoid Receptor Antagonists

Objective

Galectin-3 (Gal-3) is considered as a myocardial fibrosis biomarker with prognostic value in heart failure (HF). Since aldosterone is a neurohormone with established fibrotic properties, we aimed to investigate if mineralocorticoid receptor antagonists (MRAs) would modulate the prognostic value of Gal-3.

Methods

The IBLOMAVED cohort comprised 427 eligible chronic HF patients (CHF) with echocardiography and heart failure biomarkers assessments (BNP). After propensity score matching CHF patients for cardiovascular risk factors, to form balanced groups, Gal-3 levels were measured at baseline in plasma from patients treated with MRAs (MRA-Plus, n=101) or not (MRA-Neg, n=101). The primary end point was all-cause mortality with a follow-up of 3 years.

Results

Gal-3 in plasma from these patients were similar with median values of 14.0 ng/mL [IQR, 9.9–19.3] and 14.4 ng/mL [IQR, 12.3–19.8] (P = 0.132) in MRA-Neg and MRA-Plus, respectively. Patients with Gal-3 ≤17.8 ng/mL had an HR of 1 (reference group) and 1.5 [0.4–5.7] in MRA-Neg and MRA-Plus, respectively (p=0.509). Patients with Gal-3 ≥ 17.8 ng/mL had an HR of 7.4 [2.2–24.6] and 9.0 [2.9–27.8] in MRA-Plus and MRA-Neg, respectively (p=0.539) and a median survival time of 2.4 years [95%CI,1.8–2.4]. Multivariate Cox proportional hazard analysis confirmed that MRA and the interaction term between MRA treatment and Gal-3 >17.8 ng/mL were not factors associated with survival.

Conclusions

MRA treatment did not impair the prognostic value of Gal-3 assessed with a 17.8 ng/mL cut off. Gal-3 levels maintained its strong prognostic value in CHF also in patients treated with MRAs. The significance of the observed lack of an interaction between Gal-3 and treatment effect of MRAs remains to be elucidated.     

Impact of Renal Dysfunction on Mid-Term Outcome after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis

Background

There is conflicting evidence regarding the impact of preexisting renal dysfunction (RD) on mid-term outcomes after transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis (AS).

Methods and results

Forty-seven articles representing 32,131 patients with AS undergoing a TAVI procedure were included in this systematic review and meta-analysis. Pooled analyses were performed with both univariate and multivariate models, using a fixed or random effects method when appropriate. Compared with patients with normal renal function, mid-term mortality was significantly higher in patients with preexisting RD, as defined by the author (univariate hazard ratio [HR]: 1.69; 95% confidence interval [CI]: 1.50–1.90; multivariate HR: 1.47; 95% CI: 1.17–1.84), baseline estimated glomerular filtration rate (eGFR) (univariate HR: 1.65; 95% CI: 1.47–1.86; multivariate HR: 1.46; 95% CI: 1.24–1.71), and serum creatinine (univariate HR: 1.69; 95% CI: 1.48–1.92; multivariate HR: 1.65; 95% CI: 1.36–1.99). Advanced stage of chronic kidney disease (CKD stage 3–5) was strongly related to bleeding (univariate HR in CKD stage 3: 1.30, 95% CI: 1.13–1.49; in CKD stage 4: 1.30, 95% CI: 1.04–1.62), acute kidney injure (AKI) (univariate HR in CKD stage 3: 1.28, 95% CI: 1.03–1.59; in CKD stage 4: 2.27, 95% CI: 1.74–2.96), stroke (univariate HR in CKD stage 4: 3.37, 95% CI: 1.52–7.46), and mid-term mortality (univariate HR in CKD stage 3: 1.57, 95% CI: 1.26–1.95; in CKD stage 4: 2.77, 95% CI: 2.06–3.72; in CKD stage 5: 2.64, 95% CI: 1.91–3.65) compared with CKD stage 1+2. Patients with CKD stage 4 had a higher incidence of AKI (univariate HR: 1.70, 95% CI: 1.34–2.16) and all-cause death (univariate HR: 1.60, 95% CI: 1.28–1.99) compared with those with CKD stage 3. A per unit decrease in serum creatinine was also associated with a higher mortality at mid-term follow-up (univariate HR: 1.24, 95% CI: 1.18–1.30; multivariate HR: 1.19, 95% CI: 1.08–1.30).

Conclusions

Preexisting RD was associated with increased mid-term mortality after TAVI. Patients with CKD stage 4 had significantly higher incidences of peri-procedural complications and a poorer prognosis, a finding that should be factored into the clinical decision-making process regarding these patients.     

Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

Intestinal Fatty Acid-Binding Protein as a Diagnostic Marker for Complicated and Uncomplicated Necrotizing Enterocolitis: A Prospective Cohort Study

Background

Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease.

Methods

Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points.

Results

The study comprised 37 neonates (24M, 13F), gestational age 28 (24–36) weeks, birth weight 1190 (570–2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89–35) and 5.1 (95% CI 0.73–36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6–70) and 11 (95% CI 1.6–81), respectively.

Conclusions

Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.     

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections

Background

Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.

Methods

The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0–4, 5–14, 15–64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata).

Results

Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003–2004 and 2012–2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0–4 years, those aged 5–14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87–2.47) while those aged 15–64 years were less likely (OR 0.83, 95% CI 0.73–0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses.

Conclusions

Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.     

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

Objective

The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies.

Methods

Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis.

Results

The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa.

Conclusions

The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction

Background

Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP) are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using magnetic resonance imaging (MRI). Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated.

Objectives

To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF.

Methods

The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis) and 48 of the volunteers underwent determination of BPF using MRI.

Results

Mean (±SD) NFL was 355 ng/L (±214), mean GFAP was 421 ng/L (±129) and mean BPF was 0.867 (±0.035). All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance.

Conclusions

This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age.     

Predictive Value of S100-B and Copeptin for Outcomes following Seizure: The BISTRO International Cohort Study

Objective

To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure.

Methods

We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days.

Results

Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07–0.20] vs 0.09 μg/l [0.07–0.14]) and copeptin (23 pmol/l [9–104] vs 17 pmol/l [8–43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51–0.64] and 0.59 [0.54–0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1–1.5]), provoked seizure (OR 4.93 [2.5–9.8]), complex partial seizure (OR 4.09 [1.8–9.1]) and first seizure (OR 1.83 [1.1–3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80–18.9] copeptin OR 1 [1.00–1.00]).

Conclusion

The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes.     

Metabolic and Kidney Disorders Correlate with High Atazanavir Concentrations in HIV-Infected Patients: Is It Time to Revise Atazanavir Dosages?

Introduction

Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles.

Methods

We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%).

Results

43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77–555], 548 [206–902], 793 [440–1164], 768 [494–1527] and 1491 [1122–1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266–1148], and 1098 [631–1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77–541] ng/mL).

Conclusions

A significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity.     

Predictive Factors for Subjective Improvement in Lumbar Spinal Stenosis Patients with Nonsurgical Treatment: A 3-Year Prospective Cohort Study

Objective

To assess the predictive factors for subjective improvement with nonsurgical treatment in consecutive patients with lumbar spinal stenosis (LSS).

Materials and Methods

Patients with LSS were enrolled from 17 medical centres in Japan. We followed up 274 patients (151 men; mean age, 71 ± 7.4 years) for 3 years. A multivariable logistic regression model was used to assess the predictive factors for subjective symptom improvement with nonsurgical treatment.

Results

In 30% of patients, conservative treatment led to a subjective improvement in the symptoms; in 70% of patients, the symptoms remained unchanged, worsened, or required surgical treatment. The multivariable analysis of predictive factors for subjective improvement with nonsurgical treatment showed that the absence of cauda equina symptoms (only radicular symptoms) had an odds ratio (OR) of 3.31 (95% confidence interval [CI]: 1.50–7.31); absence of degenerative spondylolisthesis/scoliosis had an OR of 2.53 (95% CI: 1.13–5.65); <1-year duration of illness had an OR of 3.81 (95% CI: 1.46–9.98); and hypertension had an OR of 2.09 (95% CI: 0.92–4.78).

Conclusions

The predictive factors for subjective symptom improvement with nonsurgical treatment in LSS patients were the presence of only radicular symptoms, absence of degenerative spondylolisthesis/scoliosis, and an illness duration of <1 year.     

Blood Lead Levels in Children Aged 0–6 Years Old in Hunan Province,China from 2009–2013

Objectives

The aim of this study is to describe blood lead levels (BLLs) and the prevalence of elevated blood lead levels (EBLLs) in children aged 0–6 years old and to analyze the BLL trend in children from 2009 to 2013 in China.

Methods

A total of 124,376 children aged 0–6 years old were recruited for this study from January 1^st 2009 to December 31^st 2013. Their blood lead levels were analyzed using atomic absorption spectrometry.

Results

The median BLL was 64.3 μg/L (IQR: 49.6–81.0), and the range was 4.3–799.0 μg/L. Blood lead levels were significantly higher in boys (66.0 μg/L) than in girls (61.9 μg/L) (P<0.001). The overall prevalence of BLLs≥100 μg/L was 10.54% in children aged 0–6 years in Hunan Province. Between 2009 and 2013, the prevalence of EBLLs (≥100 μg/L) decreased from 18.31% to 4.26% in children aged 0–6 years and increased with age. The prevalence of EBLLs has dramatically decreased in two stages (2009–2010 and 2012–2013), with a slight fluctuation in 2010 and 2011.

Conclusions

Both BLLs and the prevalence of EBLLs in children aged 0–6 years old declined substantially from 2009 to 2013 in Hunan Province; however, both remain at unacceptably high levels compared to developed countries. Comprehensive strategies are required to further reduce blood lead levels in children.     

Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome

Objectives

Cholestasis has been reported during the course of congenital hypothalamic-pituitary deficiency, but crucial information is lacking regarding both its origin and prognosis. We aimed to characterize the course of cholestasis and factors contributing to it in patients with deficiency due to pituitary stalk interruption syndrome (PSIS).

Methods

We conducted a retrospective single-center, case-cohort study including 16 patients with PSIS diagnosed before one year of age. We collected clinical and biological parameters from medical records and compared the characteristics of the endocrine syndrome in PSIS patients with and without cholestasis.

Results

5/16 patients had cholestasis, all with a neonatal onset and multiple hypothalamic-pituitary deficiency. Patients with cholestasis presented with lower Apgar score and higher rate of ophthalmic malformations: 3/5 vs 1/11, p = 0.03 and 5/5 vs 4/11, p = 0.02, respectively. The plasma cortisol level was strongly decreased in patients with cholestasis: 12.4 ng/mL (8–15 ng/mL) vs 79.4 ng/mL (10–210 ng/mL), p = 0.04. Cholestasis resolved within 9 months following hormone supplementation. No development of chronic liver disease was observed during a median follow-up of 9.4 years (range, 1.3–13.3 years).

Conclusions

Cholestasis is a frequent symptom at presentation of PSIS during the neonatal period that may help earlier diagnosis and that indicates a profound cortisol deficiency.     

Vitamin D Status among Young Children Aged 1–3 Years: A Cross-Sectional Study in Wuxi,China

Background

The increasingly recognized importance of vitamin D has been discussed and vitamin D status among young children has attracted widespread attention in recent years. However, study on vitamin D status in young children aged 1–3 y is limited in China.

Objective

To evaluate the nutritional vitamin D status of young children aged 1–3 y in Wuxi, southeastern China.

Methods

A large cohort of 5,571 young children aged 1–3 y were recruited in this study who visited the child health clinics at the Wuxi Maternity and Child Health Hospital (latitude 31.57°N) during January 2014 to January 2015. Wuxi was located in southeastern China at a latitude of 31.57°N. Finger-stick blood sampling was conducted in all the subjects and serum 25-Hydroxyvitamin D (25(OH)D) levels were measured to evaluate their vitamin D status.

Results

In this study, serum 25(OH)D levels of young children at the age of 1–3 years ranged from 20.6–132.9 nmol/L (Median: 71.5 nmol/L). 16.1% of the population had vitamin D deficiency (<50 nmol/L), while 38.8% of the subjects had a sufficient (50–74.9 nmol/L) vitamin D level. An optimal vitamin D status (≥75 nmol/L) was found in 45.1% of the young children. The prevalence of vitamin D deficiency was higher in autumn (19.5%) than in summer (12.1%). There was no significant difference in vitamin D status between genders. The binary logistic regression analysis revealed that child age was strongly associated with vitamin D deficiency (adjusted OR: 1.173; 95%CI: 1.053–1.308; P = 0.004).

Conclusions

The prevalence of vitamin D deficiency was 16.1% among young children aged 1–3 y in Wuxi. Season and child age were associated with their vitamin D status. It is implied that young children should receive adequate amounts of vitamin D supplementation and spend more time outdoors to prolong the sunlight exposure when they grow older.     

Evaluation of Multiparametric Magnetic Resonance Imaging in Detection and Prediction of Prostate Cancer

Background

Although European Society of Urogenital Radiology proposed the potential of multiparametric magnetic resonance imaging (MP-MRI) as a tool in the diagnostic pathway for prostate cancer (PCa) and published a unified scoring system named Prostate Imaging Reporting and Data System (PI-RADS version 1), these still need to be validated by real-life studies.

Objective

To evaluate the role of MP-MRI in detection and prediction of PCa.

Methods

Patients with clinical suspicion of PCa who underwent prebiopsy MP-MRI from 2002 to 2009 were recruited. MP-MRI results were retrospectively assigned as overall scores using PI-RADS by two radiologists. Patients were followed and the end point was the diagnosis of PCa. Receiver operating characteristics (ROC) curve was performed to test diagnostic efficacy of MP-MRI, under results of biopsy within three months. The cox proportional hazards model was used to identify independent variables for the detection of PCa.

Results

Finally, 1113 of the 1806 enrolled patients were included for analysis. The median follow-up was 56.0 months (1–137 mo). For 582 patients biopsied within three months, area under the curve for the detection of PCa with MP-MRI was 0.88 (95% confidence interval [CI], 0.75–1.00) in group of baseline prostate specific antigen (PSA) 0.01–4.00 ng/ml (n = 31), 0.90 (95% CI, 0.84–0.95) in PSA 4.01–10.00 ng/ml (n = 142), and 0.91 (95% CI, 0.87–0.94) in PSA >10.00 ng/ml (n = 409), respectively. In the cox model adjusted for age and baseline PSA level, for the detection rate of PCa, compared with PI-RADS 1–2 (reference), the hazard ratio was 6.43 (95% CI, 4.29–9.65) for PI-RADS 3, 18.58 (95% CI, 13.36–25.84) for PI-RADS 4–5 (p < 0.001).

Conclusions

Prebiopsy MP-MRI with PI-RADS is demonstrated as a valuable diagnostic and predictive tool for PCa.     

Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

Background

Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR).Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population.

Objectives

We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population.

Methods

We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality.

Results

During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75^th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0–26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75^th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8–5.6, P = 0.13). The Harrell’s C-statistic was 0.58 (95% CI 0.45–0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71–0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1–31.3), P <0.01) and improved the model’s net reclassification index (0.89, 95% CI (0.28–1.59). These results were confirmed in the independent validation cohort.

Conclusions

Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis.     

Clinical Features for Mild Hand,Foot and Mouth Disease in China

Background

Mild hand, foot and mouth disease (HFMD) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. Clinical diagnosis of mild HFMD was made by the presenting symptoms and signs (symptoms in brief) alone. We aim to evaluate the frequencies of symptoms in a retrospective case series study.

Methods

We collected epidemiological, demographic, clinical, and laboratory data from outpatient and inpatient settings on the clinical data warehouse system. We principally described the frequencies of symptoms of mild HFMD. Correlations between symptoms with laboratory-confirmed cases were then analyzed.

Results

The clinical data warehouse system included 3649 probable cases, between 2010 and 2012, of which 956 (26.20%) were laboratory confirmed. The peak incidence was identified in children 2 years of age. A total of 370 of the 956 laboratory confirmed cases (38.70%) were associated with enterovirus 71 (EV71). Logistic regression analysis adjusted for geographical variables, age, sex, month of onset, and time from onset to diagnosis showed that the clinical features constipation (P<0.0001; adjusted OR, 95%CI (2.99, 2.28–3.91)), and blisters (P<0.0001; adjusted OR, 95%CI (2.16, 1.82–2.56)) were positively correlated with the confirmed cases.

Conclusions

This is the largest case series study, including all the guideline-mentioned symptoms of mild HFMD. Our findings suggest that blisters and constipation should be considered as potential warning signs while front-line clinicians manage surges of children diagnosed with mild HFMD during a pandemic.     

Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

Introduction

Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM.

Methods

From a prior study on patients (n = 52) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH₂O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12–55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied.

Results

The included patients had a mean GCS of 8 (range, 3–10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11) and those with a metabolic crisis (Glucose <0.8 mmol/L, LPR >25, p = 0.09). No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0–24h) and day 3 (48–72h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found.

Conclusion

In this observational cohort study, we were able to show that cerebral metabolism is frequently affected in patients with ABM. Furthermore, patients with high LPR (LPR>40) had significantly higher levels of NSE, suggesting ongoing deterioration in compromised cerebral tissue. However, the potential clinical impact of MD and biomarker monitoring in ABM patients will need to be further elaborated in larger clinical trials.     

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.