scholarly journals Human KIT+ myeloid cells facilitate visceral metastasis by melanoma

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Chun I. Yu ◽  
Jan Martinek ◽  
Te-Chia Wu ◽  
Kyung In Kim ◽  
Joshy George ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Progenitor Cell ◽  
Myeloid Cells ◽  
Cell Subset ◽  
Metastatic Tumor ◽  
Gene Signature ◽  
Therapeutic Interventions ◽  
Rna Seq ◽  
Visceral Metastasis ◽  
Improve Patient

Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Here, we show using humanized mice that colonization of distant visceral organs with melanoma is dependent upon a human CD33+CD11b+CD117+ progenitor cell subset comprising <4% of the human CD45+ leukocytes. Metastatic tumor-infiltrating CD33+ cells from patients and humanized (h)NSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNA-seq analysis identified a gene signature of a KIT/CD117–expressing CD33+ subset that correlated with decreased overall survival in a TCGA melanoma cohort. Thus, human CD33+CD11b+CD117+ myeloid cells represent a novel candidate biomarker as well as a therapeutic target for metastatic melanoma.

scholarly journals Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq

2019 ◽  
Author(s):  
Santiago J. Carmona ◽  
Imran Siddiqui ◽  
Mariia Bilous ◽  
Werner Held ◽  
David Gfeller
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Gene Signature ◽  
Therapeutic Interventions ◽  
Effector Memory ◽  
Rna Seq ◽  
Repertoire Sequencing ◽  
Definition Of ◽  
Transcriptomic Level ◽  
Meta Analyses

ABSTRACTRecent studies have proposed that tumor-specific tumor-infiltrating CD8+ T lymphocytes (CD8 TIL) can be classified into two main groups: “exhausted” TILs, characterized by high expression of the inhibitory receptors PD-1 and TIM-3 and lack of transcription factor 1 (Tcf1); and “memory-like” TILs, with self-renewal capacity and co-expressing Tcf1 and PD-1. However, a comprehensive definition of the heterogeneity existing within both tumor-specific and total CD8 TILs has yet to be clearly established.To investigate this heterogeneity at the transcriptomic level, we performed paired single-cell RNA and TCR sequencing of CD8 T cells infiltrating B16 murine melanoma tumors, including cells of known tumor specificity. Unsupervised clustering and gene signature analysis revealed four distinct CD8 TIL states - exhausted, memory-like, naïve and effector memory-like (EM-like) - and predicted novel markers, including Ly6C for the EM-like cells, that were validated by flow cytometry. Tumor-specific PMEL T cells were predominantly found within the exhausted and memory-like states but also within the EM-like state. Further, TCR repertoire sequencing revealed a large clonal expansion of exhausted, memory-like and EM-like cells with partial clonal relatedness between them. Finally, meta-analyses of public bulk and single-cell RNA-seq data suggested that anti-PD-1 treatment induces expansion of EM-like cells.Our reference map of the transcriptomic landscape of murine CD8 TILs will help interpreting future bulk and single-cell transcriptomic studies and may guide the analysis of CD8 TIL subpopulations in response to therapeutic interventions.

scholarly journals Anticancer Activity of "Ziziphus jujuba" - A Review

2021 ◽  
pp. 261-269
Author(s):  
U. Vidhya Rekha ◽  
S. Bhuminathan ◽  
P. Ravi Shankar
Keyword(s):  
Drug Resistance ◽  
Patient Outcomes ◽  
Therapeutic Interventions ◽  
Anticancer Efficacy ◽  
Wide Range ◽  
History Of ◽  
Ziziphus Jujuba ◽  
Review Study ◽  
Improve Patient ◽  
Anti Inflammation

Ziziphus jujuba Mill. (Z. jujube) is a conventional plant that has a long history of usage in nutrients and the therapeutic interventions of a wide range of ailments. It grows mainly in South and East Asia, and also in Australia and Europe. Mounting data supports the health advantages of Z. jujuba, including anticancer, anti-inflammation, anti-obesity, antioxidant, and hepato- and gastrointestinal protective characteristics. Chemotherapy, particularly with cis-diamminedichloroplatinium (CDDP, cisplatin) and its derivatives, is commonly used to treat cancer. Although it is an effective therapy for human tumors, drug resistance impedes successful treatment. A better knowledge of the processes and develop strategies to address chemoresistance can improve patient outcomes dramatically. Numerous researchers have recently focused their attention on the increasing occurrence of numerous types of malignancies worldwide. The anticancer efficacy of Z. jujuba was discussed in this review study.

Combined Approaches to the Skull Base for Intracranial Extension of Tumors via Perineural Spread can Improve Patient Outcomes

2016 ◽  
Vol 77 (S 01) ◽  
Author(s):  
Sheri Palejwala ◽  
Jonnae Barry ◽  
Crystal Rodriguez ◽  
Chandni Parikh ◽  
Stephen Goldstein ◽  
...  
Keyword(s):  
Skull Base ◽  
Patient Outcomes ◽  
Intracranial Extension ◽  
Perineural Spread ◽  
Improve Patient

Microporous Polysaccharide Hemosphere Absorbable Hemostat (AristaAH®) in Re-Operative Cardiac Surgical Procedures

2012 ◽  
Vol 9 (2) ◽  
pp. 96-98
Author(s):  
Brian A Bruckner ◽  
Matthias Loebe
Keyword(s):  
Patient Outcomes ◽  
Surgical Procedures ◽  
Systematic Approach ◽  
Surgical Intervention ◽  
Transfusion Requirement ◽  
Cardiac Surgical Procedures ◽  
Platelet Inhibitors ◽  
Hemostatic Agents ◽  
Surgical Field ◽  
Improve Patient

Patients undergoing re-operative cardiac surgical procedures present a great challenge with regard to obtaining hemostasis in the surgical field. Adhesions are ever-present and these patients are often on oral anti-coagulants and platelet inhibitors. As part of a well-planned surgical intervention, a systematic approach to hemostasis should be employed to decrease blood transfusion requirement and improve patient outcomes. Topical hemostatic agents can be a great help to the surgeon in achieving surgical field hemostasis and are increasingly being employed. Our approach, to these difficult patients, includes the systematic and planned use of AristaAH, which is a novel hemostatic agent whose use has proven safe and efficacious in our patient population.

scholarly journals How to improve emergency care to adults discharged within 24 hours? Acute Care planning in Emergency departments (The ACE study): a protocol of a participatory design study

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e041743
Author(s):  
Christina Østervang ◽  
Annmarie Touborg Lassen ◽  
Charlotte Myhre Jensen ◽  
Elisabeth Coyne ◽  
Karin Brochstedt Dieperink
Keyword(s):  
Patient Outcomes ◽  
Participatory Design ◽  
Hospital Admissions ◽  
Phase 1 ◽  
Family Needs ◽  
Focus Group Interviews ◽  
Phase 3 ◽  
Ace Study ◽  
Group Interviews ◽  
Improve Patient

IntroductionThe development of acute symptoms or changes in diseases led to feelings of fear and vulnerability and the need for health professional support. Therefore, the care provided in the acute medical and surgical areas of the emergency department (ED) is highly important as it influences the confidence of patients and families in managing everyday life after discharge. There is an increase in short-episode (<24 hours) hospital admissions, related to demographic changes and a focus on outpatient care. Clear discharge information and inclusion in treatment decisions increase the patient’s and family’s ability to understand and manage health needs after discharge, reduces the risk of readmission. This study aims to identify the needs for ED care and develop a solution to improve outcomes of patients discharged within 24 hours of admission.Methods and analysisThe study comprises the three phases of a participatory design (PD). Phase 1 aims to understand and identify patient and family needs when discharged within 24 hours of admission. A qualitative observational study will be conducted in two different EDs, followed by 20 joint interviews with patients and their families. Four focus group interviews with healthcare professionals will provide understanding of the short pathways. Findings from phase 1 will inform phase 2, which aims to develop a solution to improve patient outcomes. Three workshops gathering relevant stakeholders are arranged in the design plus development of a solution with specific outcomes. The solution will be implemented and tested in phase 3. Here we report the study protocol of phase 1 and 2.Ethics and disseminationThe study is registered with the Danish Data Protection Agency (19/22672). Approval of the project has been granted by the Regional Committees on Health Research Ethics for Southern Denmark (S-20192000–111). Findings will be published in suitable international journals and disseminated through conferences.

67 The Evolution of A Frailty Service

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
C Abbott ◽  
K Bishop ◽  
F Hill ◽  
C Finlow ◽  
R Maraj
Keyword(s):  
Cost Effectiveness ◽  
Patient Outcomes ◽  
Local Population ◽  
Management Team ◽  
Pdsa Cycle ◽  
North Wales ◽  
Number Of Patients ◽  
Constant State ◽  
Clinical Resource ◽  
Improve Patient

Abstract Introduction In September 2017 our frailty service was started within our medium sized DGH in North Wales. Working with our management team we secured a significant clinical resource including: We describe how resources, setting and staffing develop over a 2 year period in order to create a service which meets the needs of the local population. Method The service has been in a constant state of development since it has been in operation, utilising a PDSA model with regular meetings of clinical and managerial staff to analyse performance. Results With each new PDSA cycle the amount of patients reviewed has increased. With the move to AMU we increased the monthly number of patients reviewed from 29 to 172 patients reviewed, 97 of which were discharged directly from the unit. Conclusion Using QI methodology our Frailty Service has improved dramatically since its inception. We will continue to analyse how we work to improve patient outcomes and cost effectiveness.

scholarly journals Cochlear Implant Research and Development in the Twenty-first Century: A Critical Update

2021 ◽  
Vol 22 (5) ◽  
pp. 481-508
Author(s):  
Robert P. Carlyon ◽  
Tobias Goehring
Keyword(s):  
Research And Development ◽  
Patient Outcomes ◽  
Speech Processing ◽  
Turn Of The Century ◽  
First Century ◽  
Directional Microphones ◽  
Wide Range ◽  
The Subject ◽  
Processing Algorithms ◽  
Improve Patient

AbstractCochlear implants (CIs) are the world’s most successful sensory prosthesis and have been the subject of intense research and development in recent decades. We critically review the progress in CI research, and its success in improving patient outcomes, from the turn of the century to the present day. The review focuses on the processing, stimulation, and audiological methods that have been used to try to improve speech perception by human CI listeners, and on fundamental new insights in the response of the auditory system to electrical stimulation. The introduction of directional microphones and of new noise reduction and pre-processing algorithms has produced robust and sometimes substantial improvements. Novel speech-processing algorithms, the use of current-focusing methods, and individualised (patient-by-patient) deactivation of subsets of electrodes have produced more modest improvements. We argue that incremental advances have and will continue to be made, that collectively these may substantially improve patient outcomes, but that the modest size of each individual advance will require greater attention to experimental design and power. We also briefly discuss the potential and limitations of promising technologies that are currently being developed in animal models, and suggest strategies for researchers to collectively maximise the potential of CIs to improve hearing in a wide range of listening situations.

scholarly journals Integration of tumor inflammation, cell proliferation, and traditional biomarkers improves prediction of immunotherapy resistance and response

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarabjot Pabla ◽  
R. J. Seager ◽  
Erik Van Roey ◽  
Shuang Gao ◽  
Carrie Hoefer ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Cell Activation ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Host Immune Response ◽  
Gene Signature ◽  
B Cell Activation ◽  
Rna Seq ◽  
Multiple Tumor

Abstract Background Contemporary to the rapidly evolving landscape of cancer immunotherapy is the equally changing understanding of immune tumor microenvironments (TMEs) which is crucial to the success of these therapies. Their reliance on a robust host immune response necessitates clinical grade measurements of immune TMEs at diagnosis. In this study, we describe a stable tumor immunogenic profile describing immune TMEs in multiple tumor types with ability to predict clinical benefit from immune checkpoint inhibitors (ICIs). Methods A tumor immunogenic signature (TIGS) was derived from targeted RNA-sequencing (RNA-seq) and gene expression analysis of 1323 clinical solid tumor cases spanning 35 histologies using unsupervised analysis. TIGS correlation with ICI response and survival was assessed in a retrospective cohort of NSCLC, melanoma and RCC tumor blocks, alone and combined with TMB, PD-L1 IHC and cell proliferation biomarkers. Results Unsupervised clustering of RNA-seq profiles uncovered a 161 gene signature where T cell and B cell activation, IFNg, chemokine, cytokine and interleukin pathways are over-represented. Mean expression of these genes produced three distinct TIGS score categories: strong (n = 384/1323; 29.02%), moderate (n = 354/1323; 26.76%), and weak (n = 585/1323; 44.22%). Strong TIGS tumors presented an improved ICI response rate of 37% (30/81); with highest response rate advantage occurring in NSCLC (ORR = 36.6%; 16/44; p = 0.051). Similarly, overall survival for strong TIGS tumors trended upward (median = 25 months; p = 0.19). Integrating the TIGS score categories with neoplastic influence quantified via cell proliferation showed highly proliferative and strong TIGS tumors correlate with significantly higher ICI ORR than poorly proliferative and weak TIGS tumors [14.28%; p = 0.0006]. Importantly, we noted that strong TIGS and highly [median = not achieved; p = 0.025] or moderately [median = 16.2 months; p = 0.025] proliferative tumors had significantly better survival compared to weak TIGS, highly proliferative tumors [median = 7.03 months]. Importantly, TIGS discriminates subpopulations of potential ICI responders that were considered negative for response by TMB and PD-L1. Conclusions TIGS is a comprehensive and informative measurement of immune TME that effectively characterizes host immune response to ICIs in multiple tumors. The results indicate that when combined with PD-L1, TMB and cell proliferation, TIGS provides greater context of both immune and neoplastic influences on the TME for implementation into clinical practice.

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