Enhancing care for people living with HIV: current and future monitoring approaches
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
Authors: Maggiolo, Franco; Bandera, Alessandra; Bonora, Stefano; Borderi, Marco; Calcagno, Andrea; Cattelan, Annamaria; Cingolani, Antonella; Gianotti, Nicola; Lichtner, Miriam; Lo Caputo, Sergio; Madeddu, Giordano; Maggi, Paolo; Marchetti, Giulia Carla; Maserati, Renato; Nozza, Silvia; Rusconi, Stefano; Zazzi, Maurizio; Di Biagio, Antonio
Abstract
Introduction Antiretroviral therapy (ART) is the most significant advance in the medical management of HIV-1 infection. Given the fact that HIV cannot be eradicated from the body, ART has to be indefinitely maintained. New approaches need to be defined for monitoring HIV-infected individuals (PLWHIV), including clinical, virologic, immunological parameters and also ways to collect individual points of view and quality of life. Areas covered We discuss which tests may be used to improve the management of PLWHIV and respond to a comprehensive health demand. Expert opinion Viral load and CD4 counts are well-validated outcome measures and we still need them, but they do not completely depict the health status of PLWHIV. We need to better understand and to apply to clinical practice what happens in sanctuaries, what is the role of HIV DNA, what is the meaning of low-level viremia. Most of these questions do not yet have a definitive response. Further, we need to understand how to modify these variables in order to improve outcomes. Similar points may be raised for immunological measures and for tests exploring the tolerability of drugs. The goal must be the evolution from a viro/immunologic-based to a comprehensive quality-of-health-based evaluation of PLWHIV.
Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Authors: Jiang, Ai-Min; Ren, Meng-Di; Liu, Na; Gao, Huan; Wang, Jing-Jing; Zheng, Xiao-Qiang; Fu, Xiao; Liang, Xuan; Ruan, Zhi-Ping; Tian, Tao; Yao, Yu
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TPS3, TTN, and FATI were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.