Selinexor (KPT-330), an Oral Selective Inhibitor of Nuclear Export (SINE) Compound, in Combination with FOLFOX in Patients with Metastatic Colorectal Cancer (mCRC) - Final Results of the Phase I Trial SENTINEL.

Background: Selinexor is an oral Selective Inhibitor of Nuclear Export compound that specifically blocks Chromosomal Region Maintenance protein 1.

Objective: To evaluate the safety and tolerability of escalating doses of selinexor plus 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) in metastatic colorectal cancer (mCRC) patients.

Methods: In this multicenter phase I trial, mCRC patients, eligible for oxaliplatin-based treatment, were enrolled to receive oral selinexor on days 1, 3, and 8 plus mFOLFOX6 every two weeks.

HIV Mother-to-Child Transmission in Cameroon: EID Positivity Yields and Key Risk Factors by Health Service Points After Usage of POC EID Systems.

Background: Most HIV-exposed infants access early infant diagnosis (EID) through the prevention of mother-to-child transmission (PMTCT) service points. However, there are limited data on HIV positivity in non-PMTCT health care settings (pediatric wards, emergency departments, outpatient departments, tuberculosis clinics, etc.).

Pressure Injuries in the Pediatric Population: Analysis of the 2008-2018 International Pressure Ulcer Prevalence Survey Data.

Pediatric pressure injuries continue to be a worldwide healthcare problem. Studying pediatric pressure injury point prevalence may provide more insight into the problem and drive prevention strategies for at-risk pediatric patients, a truly vulnerable population. This article reports 10 years of longitudinal pediatric pressure injury prevalence data and demographics from around the world.

Efficacy and safety of dasotraline in adults with binge-eating disorder: a randomized, placebo-controlled, fixed-dose clinical trial.

Objective: The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED).

Methods: Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12.

A Machine-Learning Approach to Identify a Prognostic Cytokine Signature That Is Associated With Nivolumab Clearance in Patients With Advanced Melanoma.

Lower clearance of immune checkpoint inhibitors is a predictor of improved overall survival (OS) in patients with advanced cancer. We investigated a novel approach using machine learning to identify a baseline composite cytokine signature via clearance, which, in turn, could be associated with OS in advanced melanoma. Peripheral nivolumab clearance and cytokine data from patients treated with nivolumab in two phase III studies (n = 468 (pooled)) and another phase III study (n = 158) were used for machine-learning model development and validation, respectively.

Quality and quantity of visceral fat tissue are associated with insulin resistance and survival outcomes after chemotherapy in patients with breast cancer.

Purpose: Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism.

Methods: Cohort 1 included 106 women with breast cancer who were undergoing surgery.

How Clinical Trial Data Sharing Platforms Can Advance the Study of Biomarkers.

Although data sharing platforms host diverse data types the features of these platforms are well-suited to facilitating biomarker research. Given the current state of biomarker discovery, an innovative paradigm to accelerate biomarker discovery is to utilize platforms such as Vivli to leverage researchers' abilities to integrate certain classes of biomarkers.

Risk score system for late aortic events in patients with uncomplicated type B aortic dissection.

Objective: Several risk factors for late aortic events in patients with uncomplicated type B aortic dissection (UTBAD) have been reported; however, they remain controversial. We developed and validated a new risk prediction score system for late aortic events in patients with UTBAD.

Methods: We reviewed 187 consecutive patients diagnosed with UTBAD from 2004 to 2017 at 2 centers (derivation cohort) and 219 consecutive patients diagnosed with UTBAD from 2012 to 2016 in 4 other centers (validation cohort).

Author Correction: Development of new method to enrich human iPSC-derived renal progenitors using cell surface markers.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial.

Introduction: Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring.

Objective: We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF).

Methods: Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access).

Stereotactic Radiosurgery for Patients with 10 or More Brain Metastases.

The JLGK0901 study showed the non-inferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for 5-10 as compared to 2-4 brain metastases (BM) in terms of overall survival and most secondary endpoints [Lancet Oncol 2014;15:387-395]. A trend for patients with 5-10 tumors to undergo SRS alone has since become apparent. The next step is to reappraise whether results of SRS treatment alone for tumor numbers ≥10 differ from those for 2-9 tumors.

A Phase I/II Open-Label Study of Nivolumab in Previously Treated Advanced or Recurrent Nasopharyngeal Carcinoma and Other Solid Tumors.

Lessons Learned: Nivolumab treatment at doses of 3 mg/kg once every 2 weeks (Q2W), 240 mg Q2W, and 360 mg once every 3 weeks was well tolerated in the Chinese population, with no new safety signals identified.Comparison of intensive pharmacokinetic profiles of nivolumab at 3 mg/kg Q2W in Chinese versus global populations revealed no ethnic differences of nivolumab treatment.Nivolumab shows promising preliminary antitumor activity in nasopharyngeal carcinoma.

Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study (PRIME-V study).

A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study was conducted to evaluate the efficacy of treatment with ipragliflozin (sodium-dependent glucose transporter-2 inhibitor) versus metformin for visceral fat reduction and glycaemic control among Japanese patients with type 2 diabetes treated with sitagliptin, HbA1c levels of 7%-10%, and body mass index (BMI) ≥ 22 kg/m . Patients were randomly assigned (1:1) to receive ipragliflozin 50 mg or metformin 1000-1500 mg daily. The primary outcome was change in visceral fat area as measured by computed tomography after 24 weeks of therapy.

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia.

Pegfilgrastim is indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy. Here, safety and efficacy of MYL-1401H, a proposed pegfilgrastim biosimilar, were investigated as prophylaxis for chemotherapy-induced neutropenia. This was a phase 3, multicenter, randomized, double-blind, parallel-group equivalence trial of MYL-1401H vs European Union-sourced reference pegfilgrastim.

The Basic Science Behind Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction: A Systematic Scoping Review of Pre-Clinical Studies.

Introduction: Despite recent promising clinical results, the underlying mechanism of action of low-intensity extracorporeal shockwave therapy (Li-ESWT) for erectile dysfunction (ED) is mostly unclear and currently under investigation.

Aim: To systematically identify and evaluate evidence regarding the basic science behind Li-ESWT for ED, discuss and propose a putative mechanism of action, address the limitations, and imply insights for further investigation in the field.

Methods: Using Cochrane's methodologic recommendations on scoping studies and systematic reviews, we conducted a systematic scoping review of the literature on experimental research regarding Li-ESWT for ED and other pathologic conditions.

Vulnerable combinations of functional dopaminergic polymorphisms to late-onset treatment resistant schizophrenia.

Background: A significant portion of patients with schizophrenia who respond to initial antipsychotic treatment acquire treatment resistance. One of the possible pathogeneses of treatment-resistant schizophrenia (TRS) is antipsychotic-induced dopamine supersensitivity psychosis (Ai-DSP). Patients with this disease progression might share some genetic vulnerabilities, and thus determining individuals with higher risks of developing Ai-DSP could contribute to preventing iatrogenic development of TRS.

Displacement of the hyoid bone by muscle paralysis and lung volume increase: the effects of obesity and obstructive sleep apnea.

Study Objectives: Animal studies suggest a pivotal role of the hyoid bone in obstructive sleep apnea (OSA). We aimed to explore the role of the hyoid bone in humans by testing the hypotheses that muscle paralysis and lung volume (LV) changes displace the hyoid bone position particularly in people with obesity and/or OSA.

Methods: Fifty patients undergoing general anesthesia participated in this study (20 participants with nonobese, non-OSA; 8 people with nonobese OSA; and 22 people with obese OSA).

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study.

Background: Combination treatment with immune checkpoint inhibitors and antiangiogenic drugs has shown encouraging preliminary antitumor activity across various tumor types including advanced or metastatic renal cell carcinoma (aRCC). The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab in combination with antiangiogenic tyrosine kinase inhibitors or ipilimumab. Long-term outcomes from this study for the combination of nivolumab plus sunitinib or pazopanib in aRCC are presented.

Proposal of new clinical diagnostic criteria for POEMS syndrome.

Objective: To propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls.

Methods: This retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment. Thirty patients with chronic inflammatory demyelinating polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30 with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal plasma cell proliferation controls) were also included.

Pilot, Randomized, Blinded, Placebo-Controlled Trial Investigating the Correlation Between Acid Control and Heartburn Relief with 14 Days of Esomeprazole Treatment.

Introduction: Reflux symptoms are frequently associated with esophageal acid exposure. However, other potential causes unrelated to acid secretion are possible, and the relationship between acid control and symptomatic improvement remains unclear. This study investigated the correlation between individual intragastric pH control and heartburn relief among subjects with frequent heartburn who are likely to self-treat with over-the-counter (OTC) medications.

Comparison of meniscal extrusion and osteophyte formation at the intercondylar notch as a predictive biomarker for incidence of knee osteoarthritis-Data from the Osteoarthritis Initiative.

Background: Medial meniscal extrusion (ME) is a biomarker to predict later development of knee osteoarthritis (KOA). On the other hand, we have reported osteophyte formation at the posterior condylar notch of the femur served as a biomarker for the same purpose. The purpose of this study is to compare capacity of the two biomarkers in predicting KOA development.