A topic modeling approach reveals the dynamic T cell composition of peripheral blood during cancer immunotherapy.

We present TopicFlow, a computational framework for flow cytometry data analysis of patient blood samples for the identification of functional and dynamic topics in circulating T cell population. This framework applies a Latent Dirichlet Allocation (LDA) model, adapting the concept of topic modeling in text mining to flow cytometry. To demonstrate the utility of our method, we conducted an analysis of ∼17 million T cells collected from 138 peripheral blood samples in 51 patients with melanoma undergoing treatment with immune checkpoint inhibitors (ICIs).

Integration of peripheral blood- and tissue-based biomarkers of response to immune checkpoint blockade in urothelial carcinoma.

As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue-based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty-five pretreatment and 12 paired on-treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab. Whole tissue sections were stained with a 12-plex mIF panel, including CD8, PD-1/CD279, PD-L1/CD274, CD68, CD3, CD4, FoxP3, TCF1/7, Ki67, LAG-3, MHC-II/HLA-DR, and pancytokeratin+SOX10 to identify over three million cells.

Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma.

CD8 T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8 T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8 T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1 Ki67 effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8 T cells.

LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade.

Immune checkpoint blocking antibodies are a cornerstone in cancer treatment; however, they benefit only a subset of patients and biomarkers to guide immune checkpoint blockade (ICB) treatment choices are lacking. We designed this study to identify blood-based correlates of clinical outcome in ICB-treated patients. We performed immune profiling of 188 ICB-treated patients with melanoma using multiparametric flow cytometry to characterize immune cells in pretreatment peripheral blood.

Neuromuscular and Clinical Recovery in Thoracic Surgical Patients Reversed With Neostigmine or Sugammadex.

Background: Patients undergoing thoracoscopic procedures may be at high-risk for incomplete neuromuscular recovery and associated complications. The aim of this clinical investigation was to assess the incidence of postoperative residual neuromuscular blockade in adult thoracic surgical patients administered neostigmine or sugammadex when optimal dosing and reversal strategies for these agents were used. The effect of choice of reversal agent on hypoxemic events and signs and symptoms of muscle weakness were also determined.

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery.

Background: Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. The aim of this secondary analysis of two previous trials was to follow up with patients who had received a single intraoperative dose of either methadone or traditional opioids for complex spine or cardiac surgical procedures.

Methods: Preplanned analyses of long-term outcomes were conducted for spinal surgery patients randomized to receive 0.

Comparison of the TOFscan and the TOF-Watch SX during Recovery of Neuromuscular Function.

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Quantitative neuromuscular monitoring is required to ensure neuromuscular function has recovered completely at the time of tracheal extubation. The TOFscan (Drager Technologies, Canada) is a new three-dimensional acceleromyography device that measures movement of the thumb in multiple planes. The aim of this observational investigation was to assess the agreement between nonnormalized and normalized train-of-four values obtained with the TOF-Watch SX (Organon, Ireland) and those obtained with the TOFscan during recovery from neuromuscular blockade.

Impact of an Activity-Based Program on Health, Quality of Life, and Occupational Performance of Women Diagnosed With Cancer.

Objective: We evaluated the impact of a 1-wk activity program on the health, quality of life (QOL), and occupational performance of community-living women diagnosed with cancer.

Method: A one-group pretest-posttest repeated-measures design was used. Participants completed a functional health measure (36-Item Short Form Health Survey [SF-36]), a QOL measure (World Health Organization Quality of Life-Brief version [WHOQOL-BREF]), and an occupational performance and satisfaction measure (Canadian Occupational Performance Measure [COPM]) before and 6 wk after program completion.

Neostigmine Administration after Spontaneous Recovery to a Train-of-Four Ratio of 0.9 to 1.0: A Randomized Controlled Trial of the Effect on Neuromuscular and Clinical Recovery.

Background: When a muscle relaxant is administered to facilitate intubation, the benefits of anticholinesterase reversal must be balanced with potential risks. The aim of this double-blinded, randomized noninferiority trial was to evaluate the effect of neostigmine administration on neuromuscular function when given to patients after spontaneous recovery to a train-of-four ratio of 0.9 or greater.