Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m² for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.     

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis

Journal of Medical Ultrasonics - Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced...     

Ethnic Differences for Public Health Knowledge,Health Advocacy Skills,and Health Information Seeking Among High School Students: Community Agents of Change

Although adult health advocacy programs have been examined in communities, little is known about integrated adolescent health advocacy programs in high schools. The purpose of this study was to examine the health advocacy program impact and ethnic differences among high school students. Using a cross-sectional study, high school students participating in the school-based program completed evaluation surveys. The program domains included upstream causes of health, community assets, and public health advocacy. Bivariate analyses were conducted to examine ethnic differences for public health knowledge, health advocacy skills, and health information seeking behaviors. Using thematic analysis, open-ended survey item responses were coded to identify themes for students’ perceptions of community health. Non-Hispanic (n?=?72) and Hispanic high school students (n?=?182) in ten classes reported owning smartphones (95%) and laptops (76%). Most students (72%) reported seeking online health information. Non-Hispanic students reported significantly higher health advocacy skills for speaking with the class about health issues, identifying community services, or creating health awareness at school than Hispanic students. Non-Hispanic students were more likely to seek health information from fathers and television than Hispanic students. Hispanic students were more likely to seek health information from hospital or clinic staff than non-Hispanic students. Emergent themes included health advocacy skills, community awareness, and individual and community health changes. High schools benefit from integrating health advocacy programs into the core curriculum. Adolescents gain important skills to improve their individual health and engage in changing community health.     

Scapulothoracic and scapholunate dissociation in the ipsilateral upper limb of a trauma victim

Scapulothoracic dissociation is a rare and complex injury pattern with varied presentation.Here we describe a case of a 32-year-old male who presented with scapulothoracic dissociation associated with brachial plexus injury,along with scapholunate dissociation.We also propose an injury mechanism that might link the two injury patterns,suggesting that the association might be more than by chance.The patient was managed according to established trauma care and resuscitation protocols followed by open reduction and internal fixation of the clavicle fracture,and fixation of scapholunate dissociation and had a successful outcome at follow-up.     

All in the Levels—Programmed Death‐Ligand 1 Expression as a Biomarker for Immune Checkpoint Inhibitor Response in Patients with Gastrointestinal Cancer

Immune checkpoint inhibitors (ICIs) benefit patients with rare subsets of gastrointestinal (GI) cancer. Significant interest exists to identify predictive biomarkers that may increase the applicability of ICI therapy for these patients. Programmed death ligand 1 (PD‐L1) is one such candidate; however, this biomarker has well‐chronicled limitations. Combined positive score (CPS) ≥1 is the minimum PD‐L1 expression threshold necessary for patients with gastric or gastroesophageal junction (GEJ) cancer to qualify for treatment with pembrolizumab; however, studies suggest that patients with higher CPS scores may derive greater benefit. We present the cases of two patients, both with low tumor mutational burden, microsatellite stable, and CPS ≥70 GI tumors (cholangiocarcinoma and GEJ cancer), who have achieved excellent tumor control with pembrolizumab. We postulate that, by testing for CPS in all patients with GI cancer and identifying a CPS threshold predictive of ICI response, PD‐L1 expression could identify the patiets with GI cancer, in tissue agnostic fashion, who could benefit from ICI therapy.     

Transcatheter aortic valve replacement and cardiac conduction

Introduction: Conduction abnormalities after transcatheter aortic valve replacement (TAVR) account for a high percentage of post-TAVR complications.

Areas covered: The etiology of conduction abnormalities is closely tied to cardiac anatomy (length of membranous septum, degree of calcification, location of left bundle within the membranous septum), baseline conduction abnormalities (preprocedure right bundle branch block), and procedural variables (type of valve, depth of implant). Management of new high-grade AV block and new left bundle branch block varies by institution in the absence of consensus guidelines.

Expert opinion: Authors describe the incidence, etiology, outcomes, and management of conduction abnormalities related to aortic stenosis and TAVR.