Coagulation Factors as Predictive Markers of Poor Outcomes in Children with Acute Liver Failure.

BACKGROUND: In children, acute liver failure (ALF) is a severe condition associated with high mortality if an emergency liver transplantation (LT) is impossible. Clinical laboratory parameters and different scores or criteria are used to predict ALF evolution in children. We aimed to assess the role of coagulation factors as predictive markers of poor outcomes in children with ALF. METHODS: The prospective study included 40 children with ALF, diagnosed based on the Pediatric ALF study group criteria. Patients with emergency LT or deceased were considered with poor outcomes. For all patients, we analyzed clinical and laboratory parameters (including plasma level of factor V (FV), factor VII (FVII), and INR). We calculated the PELD (Pediatric End-stage Liver Disease) and MELD (Model for End-stage Liver Disease) scores, King's College Hospital (KCH), and Clichy criteria. We analyzed their performance in predicting a poor outcome. RESULTS: FV and FVII levels were significantly lower in children with poor outcomes than survivors (18.92 ± 19.95% vs. 10.72 ± 10.21%, p = 0.00139, respectively 46.51 ± 26.05% vs. 10.72 ± 10.21%, p = 0.00014). These parameters varied with ALF etiology, being the lowest in metabolic and infectious causes. The maximum value of INR (INR-max) was higher in children with poor outcomes than survivors (7.05 ± 3.20 vs. 2.96 ± 1.82, p = 0.000007), as it also was for the PELD/MELD score (30.06 ± 15.55 vs. 15.77 ± 9.64, p = 0.00092). FVII, FV, and INR-max had an excellent performance in predicting the poor outcome with an area under the ROC curve of 0.894, 0.816, and 0.861, respectively. KCH criteria had a higher sensitivity than Clichy criteria (92.86% vs. 50%) but lower specificity (53.85% vs. 95%). CONCLUSIONS: Our results support the role of coagulation factors (INR, FV, and FVII) as predictive markers for the fatal evolution of children with ALF and underlined the need for monitoring along with the usual liver function tests in children with ALF.

Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease.

BACKGROUND & AIMS: Both existing clinical criteria and genetic testing have significant limitations for the diagnosis of Wilson disease (WD), often creating ambiguities in patient identification and leading to delayed diagnosis and ineffective management. ATP7B protein concentration, indicated by direct measurement of surrogate peptides from patient dried blood spot samples, could provide primary evidence of WD. ATP7B concentrations were measured in patient samples from diverse backgrounds, diagnostic potential is determined, and results are compared with biochemical and genetic results from individual patients. METHODS: Two hundred and sixty-four samples from biorepositories at 3 international and 2 domestic academic centers and 150 normal controls were obtained after Institutional Review Board approval. Genetically or clinically confirmed WD patients with a Leipzig score >3 and obligate heterozygote (carriers) from affected family members were included. ATP7B peptide measurements were made by immunoaffinity enrichment mass spectrometry. RESULTS: Two ATP7B peptides were used to measure ATP7B protein concentration. Receiver operating characteristics curve analysis generates an area under the curve of 0.98. ATP7B peptide analysis of the sequence ATP7B 887 was found to have a sensitivity of 91.2%, specificity of 98.1%, positive predictive value of 98.0%, and a negative predictive value of 91.5%. In patients with normal ceruloplasmin concentrations (>20 mg/dL), 14 of 16 (87.5%) were ATP7B-deficient. In patients without clear genetic results, 94% were ATP7B-deficient. CONCLUSIONS: Quantification of ATP7B peptide effectively identified WD patients in 92.1% of presented cases and reduced ambiguities resulting from ceruloplasmin and genetic analysis. Clarity is brought to patients with ambiguous genetic results, significantly aiding in noninvasive diagnosis. A proposed diagnostic score and algorithm incorporating ATP7B peptide concentrations can be rapidly diagnostic and supplemental to current Leipzig scoring systems.

European Society for Pediatric Gastroenterology Hepatology and Nutrition's Educational Offer and the Training Syllabus.

The basic knowledge necessary for a European pediatric gastroenterologist/hepatologist/nutritionist is set-out in the training syllabus (TS) of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). We retrospectively compared the topics covered in ESPGHAN's training events between 2013 and 2016 with the basic knowledge TS items. Thirty-six initiatives including e-learning were identified. Twelve (33%) courses focused on gastroenterology, 9 (25%) on hepatology, and 10 (28%) on nutrition. Five (14%) courses covered >1 field and were classified "General." The initiatives covered 12 of 57 (21%) TS items; 31 of 57 items (54%) were partially covered; and 14 of 57 (25%) not covered. Five of 9 e-learning courses covered gastroenterology topics, whereas none covered hepatology topics. ESPGHAN's 3-year educational offer partially met the training needs listed in the TS. A coordinated educational program covering all TS items would harmonize training within Europe and would provide trainees with a professional portfolio for employment purposes.

IODINE STATUS IN PREGNANT WOMEN AFTER A DECADE OF UNIVERSAL SALT IODIZATION IN ROMANIA.

OBJECTIVE: To assess iodine status (median urinary iodine concentration) in 118 pregnant women during the third trimester from endemic or non-endemic areas, a decade after implementation of Universal Salt Iodization in Romania. SUBJECTS AND METHODS: One hundred and eighteen pregnant women in the third trimester were included in the study group (age range: 16 - 46 years, mean age: 28.78 years). Median urinary iodine concentration (UIC) and body mass index (BMI) were evaluated. Data regarding region of provenance, smoking habits during pregnancy, education level, iodized salt intake, bread intake, iodine supplements, comorbidities (iron deficiency anemia) and birth weight were assessed. Morning urine was collected to measure median UIC. The study was approved by the Local Ethics Committee. RESULTS: Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. There is a statistically significant difference between pregnant women with and without iodine supplements from rural areas (281.5 versus 196.1 mcg/L, respectively, p=0.023). In the subgroup without iodine supplementation, there was a significant difference between overweight and obese subjects vs. normal weight subjects (232.5 versus 194 mcg/L, p=0.012). Only in the subgroup with a daily intake of less than 5 slices of bread (usually containing iodized salt) we found significant differences between those with and without iodine supplements (245.2 versus 128.3 mcg/L). Iron deficiency anemia was found in 29.66% and 19.49% were current smokers during pregnancy. CONCLUSIONS: Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. The difference between the subgroup with iodine supplements and the subgroup without iodine supplements was not statistically significant, probably due to the excessive consumption of bread and other bakery products which is traditional in Romania.

Clinical significance of the antinuclear antibodies in chronic viral hepatitis B in children.

BACKGROUND: The presence of autoantibodies is frequent in chronic viral hepatitis evolution. Defining the role of autoimmunity in disease evolution or response to interferon treatment is still in debate, both in children and in adults. There are few studies about the influence of autoimmunity in children with chronic viral hepatitis. The aim of our study was to establish the clinical significance of antinuclear autoantibodies (ANA) in chronic hepatitis B in children. METHODS: We have studied 80 children with chronic hepatitis B (30 female; mean age 12.31 +/- 4.13 years). For each patient we performed haematological and biochemical tests and in 41 patients we analyzed the liver histology. The immunological parameters analyzed were: circulating immune complexes (CIC), complement, and the serum levels of immunoglobulin G, A, and M. We analysed by indirect fluorescence the presence of ANA and other autoantibodies. The response to treatment (hepatoprotectors, interferon and Lamivudine) was established depending on seroconversion to HBeAb and HBsAb. RESULTS: Positive ANA were found at baseline in 15% of the patients and during follow-up in 21.25%. In ANA-positive patients compared to those without autoantibodies we found lower levels of haemoglobin and platelet numbers (p = 0.0245, p = 0.0236, respectively), higher gamma-glutamyl-transferase level (p = 0.040) and higher CIC level (p = 0.0155). During interferon treatment 13.79% of those who initially tested ANA-negative presented ANA, compared to 2.56% in those without interferon (p = 0.042). There was no difference in response to interferon treatment according to the presence of ANA (p = 0.4201). CONCLUSIONS: Searching for ANA in children with chronic hepatitis B is a key element in describing the evolution of these patients, especially when considering interferon therapy. Interferon treatment stimulates the development of ANA, but their presence does not influence the response to this particular treatment. The role of autoimmune processes in the evolution and response to treatment of chronic hepatitis B patients remains controversial.

Chronic asymptomatic dislocation of a total hip replacement: a case report.

INTRODUCTION: Dislocation of a prosthetic hip is the second most common complication after thromboembolic disease in patients undergoing total hip arthroplasty, with an incidence reported as 0.5 to 20%. Although the period of greatest risk for dislocation has been reported to be within the first few months after surgery, late dislocation occurs more commonly then previously thought. CASE PRESENTATION: A 60-year-old man underwent a right Exeter cemented total hip replacement and was subsequently discharged after appropriate follow-up. He next presented 8 years later complaining of pain in the left groin. An anterioposterior radiograph of the pelvis revealed degenerative changes in the left hip and a dislocated right total hip replacement. The dislocated femoral component had formed a neoacetabulum within the ilium, in which it was freely articulating. He remained pain-free on this side, had 5 cm of true leg length shortening with a good range of movement and was very pleased with his hip replacement. He was later placed on the waiting list for a left total hip replacement. CONCLUSION: This case illustrates that a dislocated total hip replacement may occasionally not cause symptoms that cause significant discomfort or reduction in range of movement. The prosthetic femoral head can form a neoacetabulum allowing a full range of pain-free movement. Furthermore it emphasises that with an increased trend to earlier hospital discharge and shorter follow-up, potential complications may be missed. We urge a low index of suspicion for potential complications and suggest that regular review with radiographic follow-up should be made.

Inorganic dust exposure causes pulmonary fibrosis in smokers: analysis using light microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy.

Smoking is alleged to cause pulmonary fibrosis, but the role of inorganic dust particulates has not been adequately examined. The authors hypothesize that inorganic dust exposure is an independent risk factor for the development of fibrosis in smokers. They studied a prospective series of 34 subjects with open lung biopsies, 18 of whom had adequate lung parenchyma for evaluation. They also examined the relationships between smoking (pack-years), respiratory bronchiolitis (RB), inorganic dusts, and interstitial fibrosis. They graded RB, fibrosis, and particulate dust by means of light microscopy. They performed a semiquantitative analysis of dust burden by using scanning electron microscopy with energy-dispersive X-ray spectroscopy. A logistic regression analysis demonstrated a significant association between smoking and RB (p = .03), but not between smoking and fibrosis or between RB and fibrosis. Fibrosis was significantly associated with silica (p = .004) and titanium (p = .0006) concentrations. The results support the authors' hypothesis.

Efficacy of an acidic vaginal gel on vaginal pH and interleukin-6 levels in low-risk pregnant women: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Increased interleukin-6 (IL-6) levels and a vaginal pH of > 4.7 are associated with obstetric complications such as preterm delivery and low birth weight. Topical treatments, able to maintain a physiological vaginal pH, could help in the prevention of vaginal infections. STUDY AIM: In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of an acidic buffering vaginal gel (Miphil) on vaginal pH and IL-6 levels in pregnant women. PATIENTS AND METHODS: Seventy low-risk women pregnant with a singleton (second trimester) were enrolled in the trial. Thirty-five were randomized to the acidic gel, 2.5 g every 3 days for 12 weeks, and 35 to the corresponding placebo. Vaginal pH and vaginal IL-6 level were measured at baseline and after 12 weeks. Women were then followed until delivery. The main outcome measures were vaginal pH, vaginal pH normalization (pH < 4.5) and vaginal IL-6 levels. RESULTS: Vaginal pH at baseline was 4.6 +/- 0.4 and 4.4 +/- 0.3 in the acidic gel and the placebo group, respectively. At baseline, a total of 40% (14/35) and 22% (8/35) of women in each group, respectively, had a vaginal pH of > or = 4.7. At week 12, the vaginal pH was 4.3 +/- 0.3 in the acidic gel group and 4.3 +/- 0.3 in the placebo group (NS). The acidic gel normalized the vaginal pH in ten out of 14 women (p = 0.04) in comparison with only one out of eight women in the placebo group (NS). The acidic gel induced a significant (p < 0.02) reduction of vaginal IL-6 from 12.0 +/- 7 to 8.9 +/- 5 pg/l (-36%). In the placebo group, IL-6 increased from 9.0 +/- 5 to 13.5 +/- 6.8 pg/l (+50%) (p = 0.05). Birth weight was 2978 +/- 700 g in the placebo group and 3241 +/- 477 g in the acidic gel group (p = 0.06). CONCLUSIONS: The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL-6. Prospective and controlled trials are warranted to evaluate whether this acidic gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

A new modified live equine influenza virus vaccine: phenotypic stability, restricted spread and efficacy against heterologous virus challenge.

Flu Avert IN vaccine is a new, live attenuated virus vaccine for equine influenza. We tested this vaccine in vivo to ascertain 1) its safety and stability when subjected to serial horse to horse passage, 2) whether it spread spontaneously from horse to horse and 3) its ability to protect against heterologous equine influenza challenge viruses of epidemiological relevance. For the stability study, the vaccine was administered to 5 ponies. Nasal swabs were collected and pooled fluids administered directly to 4 successive groups of naïve ponies by intranasal inoculation. Viruses isolated from the last group retained the vaccine's full attenuation phenotype, with no reversion to the wild-type virus phenotype or production of clinical influenza disease. The vaccine virus spread spontaneously to only 1 of 13 nonvaccinated horses/ponies when these were comingled with 39 vaccinates in the same field. For the heterologous protection study, a challenge model system was utilised in which vaccinated or naïve control horses and ponies were exposed to the challenge virus by inhalation of virus-containing aerosols. Challenge viruses included influenza A/equine-2/Kentucky/98, a recent representative of the 'American' lineage of equine-2 influenza viruses; and A/equine-2/Saskatoon/90, representative of the 'Eurasian' lineage. Clinical signs among challenged animals were recorded daily using a standardised scoring protocol. With both challenge viruses, control animals reliably contracted clinical signs of influenza, whereas vaccinated animals were reliably protected from clinical disease. These results demonstrate that Flu Avert IN vaccine is safe and phenotypically stable, has low spontaneous transmissibility and is effective in protecting horses against challenge viruses representative of those in circulation worldwide.

Learning and retention of conditioned aversions by freely feeding chicks.

The present experiments assessed poison-based aversion learning and retention in freely feeding and drinking domestic chicks whose drinking water was colored blue and adulterated with LiCl for a 24-hr period. The amount of LiCl self-administered by 11-day-old chicks and their subsequent avoidance of unadulterated water of the same color was examined. The results of four experiments demonstrated that chicks self-administered large and often lethal doses of the LiCl solution. Chicks subsequently avoided blue water during two-bottle preference tests administered 3 to 7 days but not 14 days after exposure. These data indicate that neophobia alone is insufficient to prevent nondeprived chicks from ingesting large quantities of a toxin during their initial encounter with it. The lack of long-term retention in the present experiments indicates that naturally occurring aversions based on visual and illness cues, while effective in the short term, may not be a major factor in the choices made by freely feeding and drinking chicks over the long term.

Grouping based on phenomenal similarity of achromatic color.

It is widely acknowledged that a precondition for the perception of the world of objects and events is an early process of organization, and it has generally been assumed that such organization is based on the Gestalt laws of grouping. However, the stage at which such grouping occurs, whether early or late, is an empirical question. It is demonstrated in two experiments that grouping by similarity of neutral color is based not on similarity of absolute luminance at the level of the proximal stimulus, but on phenomenal similarity of lightness resulting from the achievement of lightness constancy. An alternative explanation of such grouping based on the equivalence of luminance ratios between elements and background is ruled out by appropriate control conditions.

Can we imagine how objects look from other viewpoints?

Many psychologists who study cognition believe that perception achieves object-centered representations that make it possible to extract representations of how the object would appear from differing viewpoints. Others believe we can achieve representations of how an object would appear by a process of visualization or mental rotation. We report experiments in which the subject tries to imagine how three-dimensional novel wire objects would appear from positions other than the one they are in. Subjects are unable to perform this task unless they make use of strategies that circumvent the process of visualization. It is suggested that the linear increase in time required to succeed in mental rotation tasks as a function of the angular discrepancy between the figures compared is the result of increasing difficulty rather than of the time required for rotation.