Effect of interferon-gamma on hepatic fibrosis in chronic hepatitis B virus infection: a randomized controlled study.

BACKGROUND & AIMS: Hepatic fibrosis due to chronic HBV infection has enormous socioeconomic impact. Besides strategies targeting virus elimination, prevention or reversal of liver fibrosis is amenable. Given the antifibrotic activity of interferon-gamma (IFN-gamma), a randomized open-labeled multicenter trial was initiated to test IFN-gamma in HBV infection. METHODS: HBsAg-positive patients with biopsy proven hepatic fibrosis (n = 99, stages 2-4, Scheuer criterion) were treated with diammone-glycyrrhizinate and potassium-magnesium aspartate. Sixty-six randomly assigned patients were treated with 50 mug IFN-gamma intramuscularly on a daily basis for 3 months and on alternate days the subsequent 6 months. Efficacy was evaluated by liver biopsy and serologic markers. RESULTS: Fifty-four patients in the IFN-gamma group and 29 patients in the control group completed the study. The hepatic fibrosis score was significantly reduced in 63% of IFN-gamma treated patients compared with 24.1% in the control group by using a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for the total fibrosis score decreased from 13.8 +/- 5.8 to 10.1 +/- 5.1 in the IFN-gamma group (P = .0001), whereas they were unchanged in control subjects (13.2 +/- 6.8 vs 12.6 +/- 4.8, P = .937). The Scheuer system showed 12 out of 54 patients improved >or=1 stage(s) in the IFN-gamma group compared with 1 of 29 in the control group. Antifibrotic activity might be attributed to decreased transforming growth factor-beta signaling via phosphorylated Smad2 and reduced number of activated, alpha-smooth muscle actin positive hepatic stellate cells. CONCLUSIONS: IFN-gamma treatment for 9 months improves fibrosis scores in patients with chronic HBV infection most likely by antagonizing profibrogenic transforming growth factor-beta effects.     

Temporäre mechanische Linksherzentlastung

Zusammenfassung Hintergrund  Die Implantation eines mechanischen Herzunterstützungssystem (MCSS) bei Patienten mit idiopathischer dilatativer Kardiomyopathie im Endstadium kann zu einer Verbesserung der Herzfunktion führen und die Explantation des Systems erlauben. Wir berichten über die Effekte der ventrikul?ren Entlastung auf die Herzfunktion, die humoralen Anti-β₁-Adrenozeptor-Autoantik?rper (A-β₁-AAK) sowie die myokardiale Fibrose. Methoden  13 Patienten mit nichtisch?mischer dilatativer Kardiomyopathie im Endstadium (NYHA IV-D) erhielten ein monoventrikul?res (zw?lf Patienten) oder ein biventrikul?res (ein Patient) Herzentlastungssystem. Alle hatten zur Zeit der Implantation einen Cardiac Index <1,61·min⁻¹·m² K?rperoberfl?che, eine linksventrikul?re Auswurffraktion (LVEF) von <16%, einen linksventrikul?ren enddiastolischen Diameter (LVEDd)>68 mm und einen positiven A-β₁-AAK-Nachweis. Echokardiographische Auswertungen, Serumtests auf A-β₁-AAK und histologische Untersuchungen hinsichtlich myokardialer Fibrose wurden vor und nach Implantation eines MCSS durchgeführt. Ergebnisse  Die durchschnittliche Unterstützungsdauer betrug 236±201 Tage (30 bis 794 Tage). Innerhalb dieses Zeitraums verbesserte sich die LVEF von ≤15 auf im Durchschnitt 46% und der LVEDd von 74 auf 56 mm. Die A-β₁-AAK waren nach im Mittel 11,7 Wochen im Serum nicht mehr nachweisbar. Ein Wiederanstieg konnte auch nach Explantation bei keinem Patienten beobachtet werden. Ein hochpathologischer Fibroseanteil im Myokard war etwa ein Jahr nach Explantation ebenfalls nicht mehr zu beobachten. Ein Patient dekompensierte sechs Monate nach Explantation und wurde daraufhin mit einem externen monoventrikul?ren System unterstützt. Die nachfolgende Transplantation verlief erfolgreich. Ein weiterer Patient starb unmittelbar nach Explantation an der Folge einer an?sthesiologischen Komplikation. Die mittlere Nachbeobachtungsdauer bei elf Patienten nach Explantation betr?gt (Stand 31. 5. 1997) 12,6±9,77 Monate (drei bis 26 Monate). Kumulativ konnten 139 Patientenmonate nachbeobachtet werden. Schlu?folgerung  Bei ausgew?hlten Patienten mit terminaler idiopathischer dilatativer Kardiomyopathie kann durch eine tempor?re mechanische Herzunterstützung eine weitgehende Normalisierung der Herzfunktion erreicht werden. Die pr?operative myokardiale Fibrose ist ein Jahr nach Explantation nicht mehr nachweisbar. Die A-β₁-AAK verschwinden in der Phase der mechanischen Entlastung des Herzens und treten nach Explantation des Systems nicht mehr auf. “Weaning” von der mechanischen Herzunterstützung kann eine Alternative zur Herztransplantation darstellen.      

Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study

OBJECTIVETo investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.RESEARCH DESIGN AND METHODSA comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.RESULTSThe rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]).CONCLUSIONSThe substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.     

Enhancing Social Initiations Using Naturalistic Behavioral Intervention: Outcomes from a Randomized Controlled Trial for Children with Autism

Deficits in social skills are common in children with Autism Spectrum Disorder (ASD), and there is an urgent need for effective social skills interventions, especially for improving interactions with typically developing peers. This study examined the effects of a naturalistic behavioral social skills intervention in improving social initiations to peers through a randomized controlled trial. Analyses of multimethod, multi-informant measures indicated that children in the active group (SIMI) demonstrated greater improvement in the types of initiations which were systematically prompted and reinforced during treatment (i.e., behavior regulation). Generalization to joint attention and social interaction initiation types, as well as collateral gains in broader social functioning on clinician- and parent-rated standardized measures were also observed.

     

Texture Analysis of Three-Dimensional MRI Images May Differentiate Borderline and Malignant Epithelial Ovarian Tumors

ObjectiveTo explore the value of magnetic resonance imaging (MRI)-based whole tumor texture analysis in differentiating borderline epithelial ovarian tumors (BEOTs) from FIGO stage I/II malignant epithelial ovarian tumors (MEOTs).Materials and MethodsA total of 88 patients with histopathologically confirmed ovarian epithelial tumors after surgical resection, including 30 BEOT and 58 MEOT patients, were divided into a training group (n = 62) and a test group (n = 26). The clinical and conventional MRI features were retrospectively reviewed. The texture features of tumors, based on T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging, were extracted using MaZda software and the three top weighted texture features were selected by using the Random Forest algorithm. A non-texture logistic regression model in the training group was built to include those clinical and conventional MRI variables with p value < 0.10. Subsequently, a combined model integrating non-texture information and texture features was built for the training group. The model, evaluated using patients in the training group, was then applied to patients in the test group. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the models.ResultsThe combined model showed superior performance in categorizing BEOTs and MEOTs (sensitivity, 92.5%; specificity, 86.4%; accuracy, 90.3%; area under the ROC curve [AUC], 0.962) than the non-texture model (sensitivity, 78.3%; specificity, 84.6%; accuracy, 82.3%; AUC, 0.818). The AUCs were statistically different (p value = 0.038). In the test group, the AUCs, sensitivity, specificity, and accuracy were 0.840, 73.3%, 90.1%, and 80.8% when the non-texture model was used and 0.896, 75.0%, 94.0%, and 88.5% when the combined model was used.ConclusionMRI-based texture features combined with clinical and conventional MRI features may assist in differentitating between BEOT and FIGO stage I/II MEOT patients.     

Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of “precursor escape”?

Journal of Molecular Medicine - Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from...