Evaluation of hepatic fibrosis in patients with chronic hepatitis B virus by non-invasive methods: Aspartate-to-platelet ratio index, Fibrosis-4, fibrotest and fibroscan

Background: The process of hepatic fibrosis is common to the various etiologies of chronic liver disease such as viral hepatitis B. Objective: To evaluate hepatic fibrosis by non-invasive markers such as Aspartate-to-Platelet Ratio Index (APRI), fibrosis-4 (FIB-4), fibrotest and fibroscan. Patients and Method: This was a descriptive study during a period of 32 months. Included in our study were the records of outpatients, chronic carriers of hepatitis B virus without viral co-infection C, D or HIV, followed in the Gastroenterology unit of the Campus Teaching Hospital of Lome-Togo. Results: We retained 222 patients. Among the patients, 148 patients (66.67%) were classified in Phase 3 (inactive carrying). Only 10 patients (4.50%) had a APRI score indicating a fibrosis stage ≥ F4 (presence of cirrhosis). A FIB-4 score indicating the presence of cirrhosis was found in 12 patients (5.40%). The most represented stage at fibrotest was the F0 stage (45.45%). Cirrhosis was noted in 6.06% of cases at fibroscan. Patients with APRI score ≤ 2 (96.23%) had a FIB-4 score ≤ 3.25, (p = 0.0088). Conclusion: The evaluation of hepatic fibrosis during chronic hepatopathies is essential for patients care because it influences therapeutic decisions.

First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase 3 iLLUMINATE trial

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or

Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

A Smartphone Application as an Exploratory Endpoint in a Phase 3 Parkinson’s Disease Clinical Trial: A Pilot Study

<b><i>Background:</i></b> Smartphones can generate objective measures of Parkinson’s disease (PD) and supplement traditional in-person rating scales. However, smartphone use in clinical trials has been limited. <b><i>Objective:</i></b> This study aimed to determine the feasibility of introducing a smartphone research application into a PD clinical trial and to evaluate the resulting measures. <b><i>Methods:</i></b> A smartphone application was introduced part-way into a phase 3 randomized clinical trial of inosine. The application included finger tapping, gait, and cognition tests, and participants were asked to complete an assessment battery at home and in clinic alongside the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). <b><i>Results:</i></b> Of 236 eligible participants in the parent study, 88 (37%) consented to participate, and 59 (27 randomized to inosine and 32 to placebo) completed a baseline smartphone assessment. These 59 participants collectively completed 1,292 batteries of assessments. The proportion of participants who completed at least one smartphone assessment was 61% at 3, 54% at 6, and 35% at 12 months. Finger tapping speed correlated weakly with the part III motor portion (<i>r</i> = −0.16, left hand; <i>r</i> = −0.04, right hand) and total (<i>r</i> = −0.14) MDS-UPDRS. Gait speed correlated better with the same measures (<i>r</i> = −0.25, part III motor; <i>r</i> = −0.34, total). Over 6 months, finger tapping speed, gait speed, and memory scores did not differ between those randomized to active drug or placebo. <b><i>Conclusions:</i></b> Introducing a smartphone application midway into a phase 3 clinical trial was challenging. Measures of bradykinesia and gait speed correlated modestly with traditional outcomes and were consistent with the study’s overall findings, which found no benefit of the active drug.

Fine Mapping Analysis of the MHC Region to Identify Variants Associated With Chinese Vitiligo and SLE and Association Across These Diseases

The important role of MHC in the pathogenesis of vitiligo and SLE has been confirmed in various populations. To map the most significant MHC variants associated with the risk of vitiligo and SLE, we conducted fine mapping analysis using 1117 vitiligo cases, 1046 SLE cases and 1693 healthy control subjects in the Han-MHC reference panel and 1000 Genomes Project phase 3. rs113465897 (P=1.03×10-13, OR=1.64, 95%CI =1.44–1.87) and rs3129898 (P=4.21×10-17, OR=1.93, 95%CI=1.66–2.25) were identified as being most strongly associated with vitiligo and SLE, respectively. Stepwise conditional analysis revealed additional independent signals at rs3130969(p=1.48×10-7, OR=0.69, 95%CI=0.60–0.79), HLA-DPB1*03:01 (p=1.07×10-6, OR=1.94, 95%CI=1.49–2.53) being linked to vitiligo and HLA-DQB1*0301 (P=4.53×10-7, OR=0.62, 95%CI=0.52-0.75) to SLE. Considering that epidemiological studies have confirmed comorbidities of vitiligo and SLE, we used the GCTA tool to analyse the genetic correlation between these two diseases in the HLA region, the correlation coefficient was 0.79 (P=5.99×10-10, SE=0.07), confirming their similar genetic backgrounds. Our findings highlight the value of the MHC region in vitiligo and SLE and provide a new perspective for comorbidities among autoimmune diseases.