Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Bakground & aims Although discrimination of the model for end stage liver disease (MELD) is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discrimination and calibration performance of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intra-hepatic portosystemic shunt (TIPS); classic MELD-Mayo; MELD-UNOS, used by United Network for Organ Sharing (UNOS). Recalibration and model updating were also explored. Methods 776 patients submitted to elective TIPS (TIPS cohort), and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results Major patient characteristics in TIPS/non-TIPS cohorts were: viral etiology 402/188, alcoholic 185/130, NASH 65/33; mean follow-up± SD 25±9/19±21months; 3-6-12 month mortality were respectively, 57-102-142/31-47-99. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post-hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used for a MELD updating. Conclusions In this validation study the MELD performance was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for a MELD updating are proposed. Lay summary While discrimination performance of the Model for End Stage Liver Disease (MELD) is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in two independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis and propose a validated model recalibration. Candidate variables for a MELD updating are proposed

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate

Prenatal diagnosis of hemoglobinopathies: from fetoscopy to coelocentesis

Prenatal diagnosis of hemoglobinopathies involves the study of fetal material from blood, amniocytes, trophoblast coelomatic cells and fetal DNA in maternal circulation. Its first application dates back to the 70s and it involves globin chain synthesis analysis on fetal blood. In the 1980s molecular analysis was introduced as well as amniocentesis and chorionic villi sampling under high-resolution ultrasound imaging. The application of direct sequencing and polymerase chain reactionbased methodologies improved the DNA analysis procedures and reduced the sampling age for invasive prenatal diagnosis from 18 to 16- 11 weeks allowing fetal genotyping within the first trimester of pregnancy. In the last years, fetal material obtained at 7-8 weeks of gestation by coelocentesis and isolation of fetal cells has provided new platforms on which to develop diagnostic capabilities while non-invasive technologies using fetal DNA in maternal circulation are starting to develop

AISF position paper on HCV in immunocompromised patients

This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era