A National Survey on Point of Care Ultrasonography Use Among Veterans Affairs Clinicians in Home Care and Skilled Nursing Facilities.

INTRODUCTION: Older adults who are homebound and those in skilled nursing facilities (SNFs) often have limited access to point of care imaging to inform clinical decision making. Point-of-care ultrasonography (POCUS) can help span this gap by augmenting the physical examination to aid in diagnosis and triaging. Although training in POCUS for medical trainees is becoming more common and may focus on settings such as the emergency department, intensive care unit, and inpatient care, little is known about POCUS training among practicing clinicians who work outside of these settings. We conducted a national needs assessment survey around experience with POCUS focused on practicing clinicians in the sub-acute, long-term, and home-based care settings in the Veterans Affairs (VA) health system. METHODS: An electronic survey was developed and sent out to clinicians via Listservs for the VA long-term and sub-acute care facilities [Community Living Centers (CLCs)], Home Based Primary Care outpatient teams, and Hospital in Home teams to assess current attitudes, previous training, and skills related to POCUS. RESULTS: Eighty-eight participants responded to the survey, for an overall response rate of 29% based on the number of emails on each Listserv, representing CLC, home-based primary care, and hospital in home. Sixty percent of clinicians reported no experience with POCUS, and 76% reported that POCUS and POCUS training would be useful to their practice. More than 50% cited lack of training and lack of equipment as 2 significant barriers to POCUS use. DISCUSSION: This national needs assessment survey of VA clinicians reveals important opportunities for training in POCUS for clinicians working with older adults who are receiving home care homebound or living in SNFs.

A comprehensive update on genetic inheritance, epigenetic factors, associated pathology, and recent therapeutic intervention by gene therapy in schizophrenia.

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors. The molecular and neural pathways linked to the regulation of schizophrenia have been extensively studied. Over 180 Schizophrenic risk loci have now been recognized due to several genome-wide association studies (GWAS). It has been observed that multiple transcription factors (TF) binding-disrupting single nucleotide polymorphisms (SNPs) have been related to gene expression responsible for the disease in cerebral complexes. Copy number variation, SNP defects, and epigenetic changes in chromosomes may cause overexpression or underexpression of certain genes responsible for the disease. Nowadays, gene therapy is being implemented for its treatment as several of these genetic defects have been identified. Scientists are trying to use viral vectors, miRNA, siRNA, and CRISPR technology. In addition, nanotechnology is also being applied to target such genes. The primary aim of such targeting was to either delete or silence such hyperactive genes or induce certain genes that inhibit the expression of these genes. There are challenges in delivering the gene/DNA to the site of action in the brain, and scientists are working to resolve the same. The present article describes the basics regarding the disease, its causes and factors responsible, and the gene therapy solutions available to treat this disease.

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient's overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patients were characterized through morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics to delineate cancer cell lineage from other rare cells originating in the TME. We show that we can detect epithelial circulating tumor cells (EPI.CTC), CTCs undergoing epithelial-to-mesenchymal transition (EMT.CTC) and circulating endothelial cells (CECs) using a universal rare event detection platform (HDSCA). Longitudinal analysis of an index patient finds that CTCs are present at the time of disease progression, while CECs are predominately present at the time of stable disease. In a small cohort of prostate and breast cancer patients, we find high inter-patient and temporal intra-patient variability in the expression of tissue specific markers such as ER, HER2, AR, PSA and PSMA and EpCAM. Our study stresses the importance of the multi-omic characterization of circulating rare cells in patients with breast and prostate carcinomas, specifically highlighting overlapping and cell type defining proteo-genomic characteristics of CTCs and CECs.

Hypothyroidism in Head and Neck Squamous Cell Carcinoma Patients Receiving Radiotherapy With or Without Immune Checkpoint Inhibitors.

OBJECTIVES/HYPOTHESIS: Hypothyroidism is a relatively common complication of head and neck squamous cell carcinoma (HNSCC) treatment. The objective of this study was to determine whether the addition of programmed death ligand-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibition (anti-PD-1/PD-L1 therapy) to standard treatment increases the risk of hypothyroidism in HNSCC. STUDY DESIGN: Retrospective Cohort. METHODS: This is a retrospective, single institutional cohort study. Patients who received radiotherapy (RT) for HNSCC were identified in the electronic medical record. Patient factors collected include age, sex, body mass index (BMI), smoking status, alcohol use, Charlson comorbidity index, and HNSCC treatment records. The rate of hypothyroidism for patients with HNSCC receiving RT (+/- chemotherapy and surgery) (RT group, n = 101) was compared to that of HNSCC patients receiving RT (+/- chemotherapy and surgery) + anti-PD-1/PD-L1 therapy, either concurrently or after RT (RT + anti-PD-1/PD-L1 group, n = 38). RESULTS: There was no significant difference in the rate of clinical or subclinical hypothyroidism between the two groups. Multinomial logistic regression found no significant difference in hypothyroidism based on age, sex, or BMI. CONCLUSIONS: The addition of anti-PD-1/PD-L1 therapy to standard HNSCC treatment does not significantly increase the risk of developing hypothyroidism. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2413-E2419, 2021.