Multicenter, single-arm, phase II study (CAP) of radiotherapy plus liposomal irinotecan followed by camrelizumab and anti-angiogenic treatment in advanced solid tumors.

Introduction: Combination therapeutic mode is likely to be the key to enhance the efficacy of immunotherapy in a wider range of cancer patients. Herein, we conducted an open-label, single-arm, multicenter, phase II clinical trial that enrolled patients with advanced solid tumors who had progressed after standard treatments.

Methods: Radiotherapy of 24 Gy/3 fractions/3-10 days was given to the targeted lesions.

Predicting heart failure onset in the general population using a novel data-mining artificial intelligence method.

We aimed to identify combinations of clinical factors that predict heart failure (HF) onset using a novel limitless-arity multiple-testing procedure (LAMP). We also determined if increases in numbers of predictive combinations of factors increases the probability of developing HF. We recruited people without HF who received health check-ups in 2010, who were followed annually for 4 years.

First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.

Background: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

Methods: This was a multicenter phase 1 study.

Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.

Background: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted.

Methods: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months.

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.

Background: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs.

Methods: We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included.

Urinary catheterization prior to PCI worsens clinical outcomes in patients with acute myocardial infarction.

Background: Indwelling urethral catheters (IUCs) are used to measure urine volume, keep patients on bed rest, or keep the groin area clean in patients with acute myocardial infarction (AMI). However, the association between IUC use and in-hospital urinary-related complications is unknown.

Methods: This was a single-center retrospective analysis of 303 patients admitted to our hospital in 2018-2020 who had AMI without cardiogenic shock.

Comparison of dynamic changes in the peripheral CD8 T cells function and differentiation in ESCC patients treated with radiotherapy combined with anti-PD-1 antibody or concurrent chemoradiotherapy.

Objective: The systematic immune status of cancer patients undergoing immunotherapy is little known. We prospectively identified the function and differentiation traits of peripheral CD8 T cells based on our phase 1b clinical trial (NCT03222440) of radiotherapy combined with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and compared it with concurrent chemoradiotherapy (CCRT).

Methods: 19 and 18 patients were included in the cohort of radiotherapy plus camrelizumab and cohort of CCRT treatment.

SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy.

Introduction: Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old.

Efficacy and safety of camrelizumab plus apatinib in previously treated patients with advanced non-small cell lung cancer harboring or genetic aberration.

Background: Camrelizumab plus apatinib shows encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced non-small cell lung cancer (NSCLC); however, clinical benefits from this combination regimen in NSCLC patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) have not been reported. We assessed the efficacy and safety of this combined regimen in pretreated patients with advanced NSCLC and defined EGFR/ALK status (EGFR+/ALK+) in a phase 1b/2 trial.

Methods: Previously treated patients with advanced EGFR+/ALK+ NSCLC were enrolled and given camrelizumab 200 mg intravenously every 2 weeks plus apatinib at the recommended dose of 250 mg orally once daily.

Feasibility of Nitroglycerin Patch as a Pretreatment for the Distal Radial Approach: Study Protocol for a Randomized Controlled Trial (DRANG Study).

Background: The distal radial approach (DRA) is a novel catheter cannulation technique to access the distal radial artery for coronary angiography (CAG). It is associated with less occurrence of puncture site occlusion than the conventional transradial approach. However, cannulation failure occasionally occurs due to difficulty in puncturing the smaller distal radial artery.

Efficacy and safety of camrelizumab plus apatinib as second-line treatment for advanced squamous non-small cell lung cancer.

Background: Limited data are available for the combination regimen of anti-programmed cell death protein 1 (PD-1) inhibitor and anti-angiogenic agents as second-line therapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC), especially in patients with squamous NSCLC. This study assessed the efficacy and safety of camrelizumab plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) as second-line treatment in patients with advanced squamous NSCLC.

Methods: In the Cohort 3 from a phase II dose-expansion trial, patients with advanced non-central squamous NSCLC who were immunotherapy naïve and had failed prior first-line platinum-based chemotherapy received 200 mg of camrelizumab intravenously every 2 weeks plus oral apatinib at the recommended dose of 250 mg once daily.

Daily self-monitoring of blood pressure decreases systolic and diastolic blood pressure in hypertensive participants.

Hypertension is a major risk factor for cardiovascular diseases, and behavior modification has been shown to improve blood pressure (BP). We investigated whether daily self-monitoring of systemic BP and other factors related to cardiovascular events decreased BP in hypertensive participants. In this prospective, randomized, open, blinded-endpoint trial, we assigned 161 participants with hypertension to monitor their BP daily (BP-measurement group) or, in addition to BP, monitor their body fat, sleeping time, and daily step count (multiple-measurement group) or no self-monitoring (control group) for 2 months.

Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study.

Background: Combination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial.

Methods: Eligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily).

Review of Clinical Equipoise: Examples from Oncology Trials.

Background: The current standards that govern clinical research have been shaped over the years through many historical, social, and political events. The third principle of the Belmont Report, Justice, guides the scientific community toward the equal distribution of benefits and risks in research involving human subjects. Clinical equipoise is the status of genuine uncertainty by the investigator about the superiority of one treatment arm over the other.

α1-Adrenergic receptor mediates adipose-derived stem cell sheet-induced protection against chronic heart failure after myocardial infarction in rats.

Cell-based therapy using adipose-derived stem cells (ADSCs) has emerged as a novel therapeutic approach to treat heart failure after myocardial infarction (MI). The purpose of this study was to determine whether inhibition of α1-adrenergic receptors (α1-ARs) in ADSCs attenuates ADSC sheet-induced improvements in cardiac functions and inhibition of remodeling after MI. ADSCs were isolated from fat tissues of Lewis rats.

ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis.

Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin-proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated.

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study.

Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.

Objectives: Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models.

Costs of implementing community-based intervention for HIV testing in sub-Saharan Africa: a systematic review.

Background: Community-based interventions (CBIs) are interventions aimed at improving the well-being of people in a community. CBIs for HIV testing seek to increase the availability of testing services to populations that have been identified as at high risk by reaching them in homes, schools, or community centers. However, evidence for a detailed cost analysis of these community-based interventions in sub-Saharan Africa (SSA) is limited.

Study Protocol for a Multicenter, Open-Label, Single-Arm Study of Tranilast for Cardiomyopathy of Muscular Dystrophy.

Duchenne (DMD) and other forms of muscular dystrophy (MD) are collectively rare and affect approx imately 20 per 100,000 people. The on-going development of exon skipping and other novel therapies for DMD is expected to lead to improvements in motor function prognosis. However, improvements in motor dysfunction with these novel therapies are associated with the risk of increase in cardiac burden.

ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAF-mutant melanoma, they are ineffective in non-BRAF mutant cells. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAF- and NRAS-mutant melanomas.