PR3-ANCA: A Promising Biomarker in Primary Sclerosing Cholangitis (PSC)

Background and Aims

The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients.

Methods

A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF.

Results

When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn''s disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes.

Conclusion

PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.     

Angiographic Lesion Complexity Score and In-Hospital Outcomes after Percutaneous Coronary Intervention

Objective

We devised a percutaneous coronary intervention (PCI) scoring system based on angiographic lesion complexity and assessed its association with in-hospital complications.

Background

Although PCI is finding increasing application in patients with coronary artery disease, lesion complexity can lead to in-hospital complications.

Methods

Data from 3692 PCI patients were scored based on lesion complexity, defined by bifurcation, chronic total occlusion, type C, and left main lesion, along with acute thrombus in the presence of ST-segment elevation myocardial infarction (1 point assigned for each variable).

Results

The patients’ mean age was 67.5 +/- 10.8 years; 79.8% were male. About half of the patients (50.3%) presented with an acute coronary syndrome, and 2218 (60.1%) underwent PCI for at least one complex lesion. The patients in the higher-risk score groups were older (p < 0.001) and had present or previous heart failure (p = 0.02 and p = 0.01, respectively). Higher-risk score groups had significantly higher in-hospital event rates for death, heart failure, and cardiogenic shock (from 0 to 4 risk score; 1.7%, 4.5%, 6.3%, 7.1%, 40%, p < 0.001); bleeding with a hemoglobin decrease of >3.0 g/dL (3.1%, 11.0%, 13.1%, 10.3%, 28.6%, p < 0.001); and postoperative myocardial infarction (1.5%, 3.1%, 3.8%, 3.8%, 10%, p = 0.004), respectively. The association with adverse outcomes persisted after adjustment for known clinical predictors (odds ratio 1.72, p < 0.001).

Conclusion

The complexity score was cumulatively associated with in-hospital mortality and complication rate and could be used for event prediction in PCI patients.     

Effect of a Neonatal Resuscitation Course on Healthcare Providers’ Performances Assessed by Video Recording in a Low-Resource Setting

Background

We assessed the effect of an adapted neonatal resuscitation program (NRP) course on healthcare providers’ performances in a low-resource setting through the use of video recording.

Methods

A video recorder, mounted to the radiant warmers in the delivery rooms at Beira Central Hospital, Mozambique, was used to record all resuscitations. One-hundred resuscitations (50 before and 50 after participation in an adapted NRP course) were collected and assessed based on a previously published score.

Results

All 100 neonates received initial steps; from these, 77 and 32 needed bag-mask ventilation (BMV) and chest compressions (CC), respectively. There was a significant improvement in resuscitation scores in all levels of resuscitation from before to after the course: for “initial steps”, the score increased from 33% (IQR 28–39) to 44% (IQR 39–56), p<0.0001; for BMV, from 20% (20–40) to 40% (40–60), p = 0.001; and for CC, from 0% (0–10) to 20% (0–50), p = 0.01. Times of resuscitative interventions after the course were improved in comparison to those obtained before the course, but remained non-compliant with the recommended algorithm.

Conclusions

Although resuscitations remained below the recommended standards in terms of quality and time of execution, clinical practice of healthcare providers improved after participation in an adapted NRP course. Video recording was well-accepted by the staff, useful for objective assessment of performance during resuscitation, and can be used as an educational tool in a low-resource setting.     

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

Purpose

The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.

Methods

A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score.

Results

Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.

Conclusions

mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.     

Oocyte Scoring Enhances Embryo-Scoring in Predicting Pregnancy Chances with IVF Where It Counts Most

Context

Our center’s quality improvement optimization process on many occasions anecdotally suggested that oocyte assessments might enhance embryo assessment in predicting pregnancy chances with in vitro fertilization (IVF).

Objective

To prospectively compare a morphologic oocyte grading system to standard day-3 morphologic embryo assessment.

Design, Setting, Patients

We prospectively investigated in a private academically-affiliated infertility center 94 consecutive IVF cycles based on 6 criteria for oocyte quality: morphology, cytoplasm, perivitelline space (PVS), zona pellucida (ZP), polar body (PB) and oocyte size, each assigned a value of -1 (worst), 0 (average) or +1 (best), so establishing an average total oocyte score (TOS). Embryo assessment utilized grade and cell numbers of each embryo on day-3 after oocyte retrieval. Clinical pregnancy was defined by presence of at least one intrauterine gestational sac.

Interventions

Standard IVF cycles in infertile women.

Main Outcome Measures

Predictability of pregnancy based on oocyte and embryo-grading systems.

Results

Average age for all patients was 36.5 ± 7.3 years; mean oocyte yield was 7.97± 5.76; Patient specific total oocyte score (PTOS) was -1.05 ± 2.24. PTOS, adjusted for patient age, was directly related to odds of increased embryo cell numbers (OR 1.12, P = 0.025), embryo grade (OR 1.19, P < 0.001) and clinical pregnancy [OR 1.58 (95%CI 1.23 to 2.02), P < 0.001]. Restricting the analysis to day three embryos of high quality (8-cell/ good grades), TOS was still predictive of clinical pregnancy (OR 2.08 (95%CI 1.26 to 3.44, P = 0.004). Among the 69 patients with embryos of Grade 4 or better available for transfer 23 achieved Clinical Pregnancy. When the analysis was restricted to the 69 transfers with good quality embryos (≥ Grade 4) the Oocyte Scoring System (TOS) (AUC±SE 0.863±0.044, oocyte score) provided significantly greater predictive value for clinical pregnancy compared to the embryo grade alone (AUC 0.646 ± 0.072, embryo grade) p = 0.015.

Conclusions

Oocyte-scoring, thus, provides useful clinical information especially in good prognosis patients with large numbers of high quality embryos. This finding appears of particular importance at a time when many IVF centers are committing sizable investments to closed incubation systems with time-lapse photography, which are exclusively meant to define embryo morphology.     

Differentially Expressed Genes in EEC and LMS Syndromes

Objectives

Ectrodactyly ectodermal dysplasia cleft lip/palate (EEC) syndrome and limb-mammary syndrome (LMS) share a similar phenotype and the same pathogenic gene, which complicates the ability to distinguish between these diagnoses. The current study aims to identify a potential and practical clinical biomarker to distinguish EEC from LMS.

Methods

Two EEC pedigrees and one LMS pedigree that have been previously reported were reanalyzed. After confirmation of the causative mutations for these new patients, whole-genome expression microarray analysis was performed to assess the molecular genetic changes in these families.

Results

Five new patients with classic symptoms were reported, and these individuals exhibited the same mutation as their relatives (c.812 G>C; c.611G>A; and c.680G>A). According to the whole genome expression results, the EEC patients exhibited different gene expression characteristics compared with the LMS patients. More than 5,000 genes were differentially expressed (changes >2 or <0.5-fold) among the EEC patients, LMS patients and healthy individuals. The top three altered pathways have been implicated in apoptosis, the hematopoietic cell lineage and the Toll-like receptor signaling pathway.

Conclusion

Our results provide additional clinical and molecular information regarding EEC and LMS and suggest that peripheral blood cytokines may represent a promising clinical biomarker for the diagnosis of these syndromes.     

Red Blood Cell Distribution Width as a Pragmatic Marker for Outcome in Pediatric Critical Illness

Background

Red cell distribution width (RDW) is a routine laboratory measure associated with poor outcomes in adult critical illness.

Objective

We determined the utility of RDW as an early pragmatic biomarker for outcome in pediatric critical illness.

Methods

We used multivariable logistic regression to test the association of RDW on the first day of pediatric intensive care unit (PICU) admission with prolonged PICU length of stay (LOS) >48 hours and mortality. The area under the receiver operating characteristic curve (AUROC) for RDW was compared to the Pediatric Index of Mortality (PIM)-2 score.

Results

Over a 13-month period, 596 unique patients had RDW measured on the first day of PICU admission. Sepsis was an effect modifier for LOS >48 hours but not mortality. In sepsis, RDW was not associated with LOS >48 hours. For patients without sepsis, each 1% increase in RDW was associated with 1.17 (95% CI 1.06, 1.30) increased odds of LOS >48 hours. In all patients, RDW was independently associated with PICU mortality (OR 1.25, 95% CI 1.09, 1.43). The AUROC for RDW to predict LOS >48 hours and mortality was 0.61 (95% CI 0.56, 0.66) and 0.65 (95% CI 0.55, 0.75), respectively. Although the AUROC for mortality was comparable to PIM-2 (0.75, 95% CI 0.66, 0.83; p = 0.18), RDW did not increase the discriminative utility when added to PIM-2. Despite the moderate AUROC, RDW <13.4% (upper limit of lower quartile) had 53% risk of LOS >48 hours and 3.3% risk of mortality compared to patients with an RDW >15.7% (lower limit of upper quartile) who had 78% risk of LOS >48 hours and 12.9% risk of mortality (p<0.001 for both outcomes).

Conclusions

Elevated RDW was associated with outcome in pediatric critical illness and provided similar prognostic information as the more complex PIM-2 severity of illness score. Distinct RDW thresholds best discriminate low- versus high-risk patients.     

The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non-Invasive Parameters of Fibrosis Including ELF Test

Background

Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients.

Aim

This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement.

Methods

All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D’Amico stage, VITRO score, APRI and transient elastography (TE).

Results

The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2–76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001). ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI.

Conclusion

The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis.     

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke

Background

Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.

Methods

We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.

Results

Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.

Conclusion

Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.     

An Interobserver Reproducibility Analysis of Ki67 Visual Assessment in Breast Cancer

Background

Ki67 labeling index (LI) is used as a predictive marker and is associated with prognosis in breast cancer. However, standardised methodologies for measurement are lacking which has limited its application in clinical practice. In this study, we evaluated the interobserver concordance of visual assessment of Ki67 LI in breast cancer.

Methods

Ki67- immunostained slides of 160 cases of primary invasive breast cancer were visual assessed by five breast pathologists with two different methods to choose the scoring fields: (1) hot-spot score, (2) average score. Proportions of positive invasive tumor cells at 10 % intervals were scored. The intra-class correlation coefficient (ICC) was used to assess the interobserver reproducibility.

Results

(1) A perfect concordance of Ki67 LI was demonstrated according to both score methods (P<0.0001). Average score method (ICC, 0.904) demonstrated a better correlation than hot-spot score method (ICC, 0.894). (2) By respective means according to two score methods, all cases were classified into three groups (≤10%, 11%-30% and >30% Ki-67 LI). The concordance was relatively low in intermediate Ki67 LI group compared with low and high Ki67 LI groups. (3) All cases were classified into three groups by paired-difference (d) between means of hot-spot score and average score (d<5, 5≤d<10, d≥10). The consistency was observed to decrease with increasing paired-difference according to both methods.

Conclusions

Visual assessment of Ki67 LI at 10 % intervals is a candidate for a standard method in breast cancer clinical practice. Average score and hot-spot score of visual assessment both demonstrated a perfect concordance, and an overall average assessment across the whole section including hot spots may be a better method. Interobserver concordance of intermediate Ki67 LI in which most cutoffs are located for making clinical decisions was relatively low.     

Effects of a 12-Week Hatha Yoga Intervention on Metabolic Risk and Quality of Life in Hong Kong Chinese Adults with and without Metabolic Syndrome

Objective

To determine the efficacy of a 12-week Hatha yoga intervention to improve metabolic risk profiles and health-related quality of life (HRQoL) in Chinese adults with and without metabolic syndrome (MetS).

Methods

We conducted a controlled trial within an university-affiliated hospital. 173 Chinese men and women aged 18 or above were assigned to either the yoga intervention group (n = 87) or the control group (n = 86). Primary outcomes included 12-week change in metabolic risk factors and MetS z score. Secondary outcome was HRQoL (Medical Outcomes Short Form Survey at 12 weeks).

Results

The mean age of participants was 52.0 (SD 7.4, range 31-71) years. Analysis involving the entire study population revealed that the yoga group achieved greater decline in waist circumference (p<0.001), fasting glucose (p<0.01), triglycerides (p<0.05), and MetS z score (p<0.01). Yoga training also improved general health perceptions (p<0.01), physical component score (p<0.01), and social functioning (p<0.01) domains score of HRQoL. However, no significant differences between groups were observed in the mean change of systolic/diastolic blood pressures or high-density lipid protein cholesterol (all p>0.05). There were no significant differences in the intervention effects on waist circumference and MetS z score between the MetS subgroups (both p>0.05).

Conclusion

A 12-week Hatha yoga intervention improves metabolic risk profiles and HRQoL in Chinese adults with and without MetS.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12613000816752     

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Introduction

Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.

Methods

The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.

Results

The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.

Conclusion

Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.     

A Novel Model to Predict Esophageal Varices in Patients with Compensated Cirrhosis Using Acoustic Radiation Force Impulse Elastography

Background & Aims

Few noninvasive methods can accurately identify esophageal varices (EVs) in patients with compensated cirrhosis. We developed and validated a novel, acoustic radiation force impulse (ARFI) elastography-based prediction model for high-risk EVs (HEVs) in patients with compensated cirrhosis.

Methods

A total of 143 patients with compensated cirrhosis between February, 2010 and February, 2013 (training set) and 148 between June, 2010 and May, 2013 (validation set) who underwent ARFI elastography and endoscopy were prospectively recruited. Independent predictors of HEVs were used to construct a prediction model.

Results

Based on multivariate analysis, we developed two new statistical models, a varices risk score and ARFI-spleen diameter-to-platelet ratio score (ASPS), the latter of which was calculated as ARFI velocity × spleen diameter/platelet count. The area under receiver operating characteristic curve (AUROC) of the varices risk score and ASPS to predict HEVs were 0.935 (95% confidence interval [CI] 0.882–0.970) and 0.946 (95% CI 0.895–0.977), respectively. When ASPS, a simpler model with a higher AUROC, was applied in the validation set, acceptable diagnostic accuracy for HEVs was observed (AUROC = 0.814 [95% CI 0.743–0.885]). To detect HEVs, a negative predictive value of 98.3% was achieved at ASPS <2.83, whereas a positive predictive value of 100% was achieved at ASPS >5.28.

Conclusions

ASPS, a novel noninvasive ARFI-based prediction model, can accurately identify HEVs in patients with compensated cirrhosis. ASPS <2.83 may safely rule out the presence of HEVs, whereas patients with ASPS >5.28 should be considered for endoscopic examinations or appropriate prophylactic treatment.     

Consumption of Dental Treatment in Patients with Inflammatory Bowel Disease,a Register Study

Objective

The aim of this study was to compare the consumption of dental treatment among patients with Crohn´s disease (CD) or ulcerative colitis (UC) compared to age and gender matched control groups.

Design

The study group comprised 2085 patients with CD and 3161 with UC from the Uppsala-Örebro region and from the Stockholm region. The patients in the cohort were diagnosed between 1960 and 1989. Patients up to 70 years of age were included in the study. The two patients groups were compared to age- and gender-matched, randomly selected control groups from the same geographic area comprising a corresponding number of participants.

Results

CD patients had significantly higher total number of procedures registered (p < 0.000). The difference was most pronounced for removable dentures (+65%), fillings in front teeth (+52%) and endodontic treatment (+46%) when Crohn’s patients were compared to controls (p<0.001). The corresponding figures for UC patients were also a significantly higher total number of procedures (p < 0.005), more clinical examinations (p<0.000), fillings in canines and incisors (p < 0.001) and fillings in bicuspids and molars (p < 0.000).

Conclusion

This study demonstrate that CD and UC individuals use more dental treatment compared to an age-gender matched control group, and more caries-related treatments. The difference was most pronounced for restorative treatment in patients with Crohn’s.     

Platelet Count and Early Outcome in Patients with Spontaneous Cerebellar Hemorrhage: A Retrospective Study

Introduction

The importance of coagulation, hematology, and biochemical variables have been investigated in the stroke population but have not been systemically surveyed in cerebellar hemorrhage (CH) population. The aim of the study was to explore the predictive value of these factors for early outcome in this population.

Materials and Methods

Eighty patients with acute spontaneous CH were retrospectively analyzed. Clinical and laboratory data were collected on admission for analysis. The patients were divided by Glasgow outcome scale (GOS) score at discharge into the good outcome group (GOS score 4 or 5) and the poor outcome group (GOS score 1, 2, or 3). The association between early outcome and clinical or laboratory variables were investigated by binary logistic regression.

Results

There were 46 (57.5%) patients in the poor outcome group and 34 (42.5%) in the good outcome group. The platelet count (PC) was significantly lower in the poor outcome group (187.3 ± 53.0 × 10⁹/l) compared with good outcome group (244.9 ± 63.9 × 10⁹/l) (p < 0.001). Moreover, PC (OR 0.97; p = 0.004) was the strong predictor with poor early outcome.

Conclusions

We firstly show that lower PC is the independent predictor for poor early outcome in patients with spontaneous CH.     

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study

Background

In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5–6 years.

Methods

Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5–6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.

Results

In analysis adjusted for child’s physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001).

Conclusions

This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5–6 years.     

Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

Background & Aims

We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma.

Methods

Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated.

Results

After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively).

Conclusions

Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma.     

Serum Cystatin C Reflects Angiographic Coronary Collateralization in Stable Coronary Artery Disease Patients with Chronic Total Occlusion

Objective

We investigated whether and to what extent cystatin C was associated with angiographic coronary collateralization in patients with stable coronary artery disease and chronic total occlusion.

Methods

Serum levels of cystatin C and high-sensitive C-reactive protein (hsCRP) and glomerular filtration rate (GFR) were determined in 866 patients with stable angina and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3).

Results

In total, serum cystatin C was higher in patients with poor collateralization than in those with good collateralization (1.08 ± 0.32 mg/L vs. 0.90 ± 0.34 mg/L, P < 0.001), and correlated inversely with Rentrop score (adjusted Spearmen’s r = -0.145, P < 0.001). The prevalence of poor coronary collateralization increased stepwise with increasing cystatin C quartiles (P for trend < 0.001). After adjusting for age, gender, risk factors for coronary artery disease, GFR and hsCRP, serum cystatin C ≥ 0.97 mg/L remained independently associated with poor collateralization (OR 2.374, 95% CI 1.660 ~ 3.396, P < 0.001). The diagnostic value of cystatin C levels for detecting poor coronary collateralization persisted regardless of age, gender, presence or absence of diabetes, hypertension or renal dysfunction.

Conclusions

Serum cystatin C reflects angiographic coronary collateralization in patients with stable coronary artery disease, and cystatin C ≥ 0.97 mg/L indicates a great risk of poor coronary collaterals.     

Comparison of Outcomes and Costs of Ranibizumab and Aflibercept Treatment in Real-Life

Background

Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine.

Objective

To compare treatment costs and clinical outcomes of the medications when adjusting for patients’ characteristics and clinical status.

Design

Comparative study.

Setting

The largest public ophthalmologic clinic in Switzerland.

Patients

Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data.

Measurements

Patients’ underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured.

Results

We included 315 patients (19595 claims) with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8) covering the years 2006–2014. Mean age was 78 years (SD 9.3) and 200 (63.5%) were female. At baseline, the mean number of letters was 55.6 (SD 16.3) and the central retinal thickness was 400.1 μm (SD 110.1). Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85). Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95%CI: 1094.50–3255.27; p<0.001) for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73–1436.15; p = 0.627).

Conclusions

Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.     

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population

Background/Aims

Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.

Methodology/Principal Findings

Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies.

Methodology/ Methods

We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies.

Conclusions/Significance

The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.