Lancet Respir Med. 2020 Dec;8(12):e90-e91
Authors: Saketkoo LA, Alexanderson H, Lammi MR, LeSage D, Jensen K, Scholand MB, Volkmann ER, Russell AM
PMID: 33271133 [PubMed - as supplied by publisher]
J Appl Physiol (1985). 2020 Dec 03;:
Authors: Venturelli M, Amann M, Trinity JD, Ives SJ, Richardson RS
Abstract
The effect of a spinal cord injury (SCI) on vascular function has been clouded by both the physiological and mathematical bias of assessing vasodilation in arteries with differing diameters both above and below the lesion and when comparing with healthy, non-disabled controls (CTRL). Thus, we measured vascular function, with flow mediated vasodilation (FMD), in 10 SCI and 10 CTRL with all arteries matched for diameter (≈0.5cm): brachial (BA, arm, functional-limb in both groups) and popliteal artery (PA, leg, disused-limb in SCI, functional-limb in CTRL). PA %FMD was significantly attenuated in SCI (5.6±0.6%) compared to CTRL (8.4±1.3%), with no difference in the BA (SCI: 8.6±0.9%; CTRL: 8.7±0.7%). However, unlike the arm, where muscle mass was preserved, the legs of the SCI were significantly smaller than CTRL (~70%). Thus, reactive hyperemia (RH), which is heavily dependent upon the volume of muscle occluded, in the PA was attenuated in the SCI (144±22ml) compared to CTRL (258±16ml), but not different in the BA. Consequently, shear rate was significantly diminished in the PA of the SCI, such that %FMD/shear rate (vascular responsiveness) was actually greater in the SCI (1.5±0.1%・s-1) than CTRL (1.2±0.1%・s-1). Of note, this was significantly greater than both their own BA (0.9±0.1%・s-1) and that of the CTRL (0.9±0.1%・s-1). Therefore, examining vessels of similar size, this study reveals normal vascular function above the lesion and vascular dysfunction below the lesion. However, below the lesion there was, actually, evidence of increased vascular responsiveness in this population.
PMID: 33270514 [PubMed - as supplied by publisher]
Pediatr Pulmonol. 2020 Dec 03;:
Authors: Gatcliffe C, Rao A, Brigger M, Dimmock D, Hansen C, Montgomery J, Schlaberg R, Coufal NG, Farnaes L
Abstract
OBJECTIVES: To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. We hypothesize that using a metagenomics platform will aid in the identification of microbes not found on standard culture.
STUDY DESIGN AND METHODS: Twenty-four children referred to an aerodigestive clinic were enrolled in a prospective, single-site, cross-sectional cohort study. At the time of clinical evaluation under anesthesia, two samples were obtained: an upper airway sample and a sample from bronchoalveolar lavage (BAL). Samples were sent for routine culture and analyzed using Explify® Respiratory, a CLIA Laboratory Developed Test (LDT) which identifies respiratory commensals and pathogens through RNA and DNA sequencing. Since RNA was sequenced in the course of the metagenomic analysis to identify organisms (RNA viruses and bacteria), the sequencing approach also captured host derived mRNA during sample analysis. This incidentally obtained host transcriptomic data were analyzed to evaluate the host immune response. The results of these studies were correlated with the clinical presentation of the research subjects.
RESULTS: In ten patients, organisms primarily associated with oral flora were identified in the BAL. Standard culture was negative in three patients where clinical metagenomics led to a result with potential clinical significance. Transcriptomic data correlated with the presence or absence of dysphagia as identified on prior videofluoroscopic evaluation of swallowing.
CONCLUSIONS: Clinical metagenomics allows for simultaneous analysis of the microbiota and the host immune response from BAL samples. As the technologies in this field continue to advance, such testing may improve the diagnostic evaluation of patients with suspected chronic aspiration. This article is protected by copyright. All rights reserved.
PMID: 33270378 [PubMed - as supplied by publisher]
J Immunother Cancer. 2020 Dec;8(2):
Authors: Hu-Lieskovan S, Bhaumik S, Dhodapkar K, Grivel JJB, Gupta S, Hanks BA, Janetzki S, Kleen TO, Koguchi Y, Lund AW, Maccalli C, Mahnke YD, Novosiadly RD, Selvan SR, Sims T, Zhao Y, Maecker HT
Abstract
Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.
PMID: 33268350 [PubMed - in process]
