Pembrolizumab for recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus: a drug safety evaluation.

INTRODUCTION: The prognosis of advanced esophageal squamous cell carcinoma (ESCC) remains poor and few effective drugs are available. Cisplatin plus 5-FU (CF) has been the standard first-line treatment for advanced ESCC. However, in the KEYNOTE-181 trial, the clinical outcomes were better in patients with programmed death ligand 1 (PD-L1)-positive advanced ESCC who received pembrolizumab, an immune checkpoint inhibitor (ICI), than in those who received cytotoxic agents as second-line treatment. Moreover, the KEYNOTE-590 trial demonstrated the superiority of pembrolizumab plus CF over CF alone in terms of overall survival. Based on the results of KEYNOTE-590, pembrolizumab plus CF has become one of the standard treatments for advanced ESCC. However, the safety profile of ICI-containing therapy is different from that of conventional cytotoxic agents. AREAS COVERED: Safety of pembrolizumab-containing therapies in patients with advanced ESCC. EXPERT OPINION: Pembrolizumab-containing therapies are tolerable as first- and second-line treatments in patients with advanced ESCC. Although infrequent, immune-related adverse events may occur in patients on pembrolizumab-containing therapies. These events are potentially fatal and require treatment with steroids or immunosuppressive drugs. Regular physical and laboratory examinations, including measurement of hormone levels, are needed during and after pembrolizumab-containing therapies in clinical practice.

Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.

Endotracheal granulation after tracheostomy in acute respiratory distress syndrome from COVID-19.

Granulation tissue formation is one of the late complications of tracheostomy. It can cause stomal stenosis secondary to chondritis because of disproportionate excision of the anterior cartilage. Clinicians should carefully determine the incision point, which is typically located half way between the cricoid cartilage and the sternal notch.

[Polymer Gel Dosimetry for the High-Dose-Rate Brachytherapy Using Ir-192 Source].

High-dose-rate (HDR) brachytherapy is performed with the remote after-loading system (RALS) to transport an Ir-192 source directly to inside or near the tumor. Quality assurance (QA) of equipment should be performed at sufficient frequency to ensuring safety and quality of HDR brachytherapy treatment. Polymer gel dosimeters have been attracting attention in recent years as a QA tools of HDR brachytherapy, because they can measure the three-dimensional steep dose gradients around HDR sources. In this paper, we introduce our preliminary results using VIPET polymer gel dosimeters for Ir-192 HDR brachytherapy dosimetry.

Automatic estimation of position and orientation of an acoustic source by a microphone array network.

A method which automatically provides the position and orientation of a directional acoustic source in an enclosed environment is proposed. In this method, different combinations of the estimated parameters from the received signals and the microphone positions of each array are used as inputs to the artificial neural network (ANN). The estimated parameters are composed of time delay estimates (TDEs), source position estimates, distance estimates, and energy features. The outputs of the ANN are the source orientation (one out of four possible orientations shifted by 90 degrees and either the best array which is defined as the nearest to the source) or the source position in two dimensional/three dimensional (2D/3D) space. This paper studies the position and orientation estimation performances of the ANN for different input/output combinations (and different numbers of hidden units). The best combination of parameters (TDEs and microphone positions) yields 21.8% reduction in the average position error compared to the following baselines and a correct orientation ratio greater than 99%. Position localization baselines consist of a time delay of arrival based method with an average position error of 34.1 cm and the steered response power with phase transform method with an average position error of 29.8 cm in 3D space.

Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin.

Cellular uptake of sepiapterin resulted in an efficient accumulation of tetrahydrobiopterin. Tetrahydrobiopterin is much less permeable across the cell membrane than sepiapterin or dihydrobiopterin, the precursors of the tetrahydrobiopterin-salvage pathway. The uptake of sepiapterin by the cell was examined under metabolic arrest with N-acetylserotonin, an inhibitor of sepiapterin reductase. The release profile of previously accumulated sepiapterin was also analyzed. Two routes were clearly distinguishable, namely rapid and slow. Both were apparently bi-directional and equilibrating in type. Each route was connected to non-mixable pools somehow separated in the cell. The rapid process was too fast to analyze by the current methods of cell handling. The slower process was associated with conversion of sepiapterin to tetrahydrobiopterin in the absence of N-acetylserotonin, suggesting that this route opens into the cytosolic compartment where use of the salvage pathway was strongly driven by sepiapterin reductase and dihydrofolate reductase with a supply of NADPH which favors tetrahydrobiopterin accumulation. Consequently, sepiapterin was enforcedly taken up by the cell where it accumulated tetrahydrobiopterin in the cytosol in continuous manner.

Identification of ligands binding specifically to inflammatory intestinal mucosa using phage display.

1. Even though current treatments for inflammatory bowel disease are effective, adverse reactions remain a problem. With the intention of developing a new drug delivery system, we attempted to identify molecules that are selectively adsorbed to inflamed bowel. 2. The PhD-C7C phage display peptide library was used for biopanning against mouse isolated bowel, either untreated (control) or with inflammation caused by ischaemia-reperfusion injury. One hundred clones were selected from among those obtained by two biopanning procedures and the amino acid sequences of these clones were identified by determination of the base sequences. 3. Then, 20 clones were selected by an alignment process, after which the three clones with the highest affinity for inflammatory bowel were identified. One of these three clones had significantly higher affinity for inflammatory bowel than for normal bowel. 4. In conclusion, biopanning against isolated bowel samples identified an amino acid sequence (SQSHPRH) with a specific high affinity for inflammatory bowel.