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less then 0.05). No correlation was found between fat fraction and muscle strength. The fat fraction of thigh muscles did not correlate with scores from the clinical tests nor did it correlate with the 6MWT. During follow-up, the contractile CSA of the knee extensors increased by 2%. No other statistically significant change was observed. Quantitative MRI reflects muscle function in patients with LOPD, but larger long-term studies are needed to evaluate its utility in detecting changes over time.
Colon cancer is the third most common malignant tumor in the world. Although immunotherapy has been used in cancer treatment, there is still no first-line immunotherapy method for colon cancer. Therefore, it is essential to search for potential immunotherapy targets and molecular biomarkers for early diagnosis and prognosis.
In this study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) and immune-related genes from the ImmPort database. Then we filtered genes with prognostic value and constructed an immune-related signature. Patients were classified into low- and high-risk groups, and we exerted a series of analysis between the signature and clinical phenotypes. Additionally, we used protein-protein interaction networks, gene set enrichment analysis (GSEA) and single-sample gene-set enrichment analysis (ssGSEA) to explore the underlying mechanism of this signature. Furthermore, the accuracy of this signature was verified, using two data sets from Gene Expression Omnibus (GEO).
We ssues.
Ultraportable handheld ultrasound (HHU) devices are being rapidly adopted by emergency medicine (EM) physicians. Though knowledge of the breadth of their utility and functionality is still limited compared to cart-based systems, these machines are becoming more common due to ease-of-use, extreme affordability, and improving technology.
Images obtained with HHU are comparable to those obtained with traditional machines but create unique issues regarding billing and data management. HHU devices are increasingly used successfully to augment the education of practitioners-in-training, by emergency physicians in austere environments, and in the burgeoning fields of "tele-ultrasound" and augmented reality scanning.
This review seeks to describe the current state of use of HHU devices in the emergency department (ED) including device overview, institutional concerns, unique areas of use, recent literature since their adoption into clinical EM, and their future potential.
This review seeks to describe the current state of use of HHU devices in the emergency department (ED) including device overview, institutional concerns, unique areas of use, recent literature since their adoption into clinical EM, and their future potential.
To review the current prevalence, trends, perceptions, and effects of e-cigarette or vaping product use associated lung injury (EVALI) on e-cigarette use among US adolescents and young adults.
COVID-19 diagnosis was more likely among the current/ever dual cigarette and e-cigarettes users, as well as ever e-cigarette only users. Additionally, the EVALI outbreak may have influenced harm perceptions, as daily nicotine vaping declined significantly from 2019 to 2020, and more youth and young adults perceived vaping as harmful.
The prevalence of e-cigarette use, specifically flavored use, remains high among adolescents and young adults, which is concerning due to the short-term and unknown long-term effects of e-cigarettes and their association with future cigarette and other substance use.
The prevalence of e-cigarette use, specifically flavored use, remains high among adolescents and young adults, which is concerning due to the short-term and unknown long-term effects of e-cigarettes and their association with future cigarette and other substance use.
Patients from various countries may have unique patterns of using complementary and alternative medicine (CAM) and unique reasons for using it.
Our objective was to assess the use of CAM among patients from the Gulf region attending the Executive and International Health Program of the Department of General Internal Medicine at Mayo Clinic in Rochester, Minnesota.
This cross-sectional survey was administered to all patients who were from the Gulf region and were undergoing outpatient evaluation in the Executive and International Health Program. After their initial medical evaluation by a physician, the patients were invited to anonymously complete the modified International Complementary and Alternative Medicine Questionnaire.
The survey was completed by 69 patients (41 women, 27 men; mean age, 45.4 years). The most frequently seen providers for CAM treatments were physicians (71.0% of patients), spiritual healers (29.0%), and chiropractors (20.3%). CAM treatments most frequently received from a physiom the Gulf region should be aware of how the use of CAM may affect the care needs of these patients.Metastasis is the leading cause of cancer mortality. We have investigated the tumor microenvironment at all metastatic cascade steps (early-metastasic dissemination, synchronous metastasis, metachronous metastasis) to delineate the impact of tumor and immune parameters to this process. Tumors with and without signs of early metastasis invasion (venous-emboli, lymphatic-invasion, perineural-invasion, collectively, VELIPI) had similar levels of inflammatory and immunosuppressive molecules. Cancer mutations, gene expression levels or chromosomal instability did not significantly differ in primary tumors from patients with or without metastasis. In contrast, tumors without early metastasis invasion were highly infiltrated with Th1 and memory T cells and were associated with a good outcome. A cytotoxic immune signature, Immunoscore and increased lymphatic vessels at the invasive margin of tumors, protected against the generation of distant metastases. The metastatic landscape was highly heterogeneous, each of the metastases of a patient bearing diverse tumor-cell clones and diverse immune-microenvironments. The Immunoscore within a random metastasis significantly predicted major differences in patient's survival, and Immunoscore from the least immune-infiltrated metastasis was the most associated with patient long-term survival. We proposed an alternative theory of tumor evolution, where an immune selection model best-described tumor evolution in humans. Metachronous metastasis revealed that immunoedited tumor clones are eliminated, while the immune privileged clones progress underlines relationships between clonal seeding and immune surveillance and advances the understanding of cancer evolution. A strong intratumoral immune infiltrate and Immunoscore prevent the metastatic invasion at all its steps and it is associated with prolonged survival.Most monoclonal antibodies (MAbs), including immune checkpoint inhibitor MAbs, are delivered intravenously (i.v.) to patients. Recent clinical studies have demonstrated that some anti-PD1 MAbs may also be delivered subcutaneously (s.c.), with clinical outcomes similar of those obtained with i.v.-delivered agents. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGF-βRII or TGF-β "trap") fused to the heavy chain of an IgG1 antibody blocking programmed death ligand 1 (anti-PDL1), was designed to target two key immunosuppressive pathways in the tumor microenvironment (TME). Bintrafusp alfa is currently being administered i.v. in clinical studies. The studies reported here demonstrate that systemic or s.c. delivery of bintrafusp alfa, each administered at five different doses, induces similar anti-tumor effects in breast and colorectal carcinoma models. An interrogation of the TME for CD8+ and CD4+ T cells, regulatory T cells (Tregs), monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic (G) MDSCs showed similar levels and phenotype of each cell subset when bintrafusp alfa was given systemically or s.c. Subcutaneous administration of bintrafusp alfa also sequestered TGFβ in the periphery at similar levels seen with systemic delivery. To our knowledge, this is the most comprehensive preclinical evaluation of any checkpoint inhibitor MAb given s.c. vs systemically, and the first to demonstrate this phenomenon using a bifunctional agent. These studies provide preclinical rationale to explore s.c. FDI-6 inhibitor approaches for bintrafusp alfa in the clinic.As an adverse survival prognosticator, chemokine (C-X-C motif) ligand 13 (CXCL13) has been studied in several types of malignancies. The secretion and physiological roles of CXCL13 in follicular helper T cells (TFH) cells have been well described, while the clinical significance of CD8+ tumor-infiltrating lymphocytes (TILs)-associated CXCL13 remains unknown. This study aims to investigate the clinical significance of CXCL13+CD8+ T cells in survival and chemotherapeutic responsiveness prediction in gastric cancer. In this study, 440 patients enrolled from Zhongshan Hospital with tumor microarray (TMA) specimens were randomly divided into testing set (n = 220) and validation set (n = 220) for analysis. CXCL13+CD8+ T cells were detected by multicolor immunohistochemistry. Fresh tumor tissue samples from another 60 gastric cancer patients were collected to detect CXCL13+CD8+ T cells functional status by flow cytometry (FCM). We found that high intratumoral CXCL13+CD8+ T cells infiltration predicted poor overall survival and inferior chemotherapeutic responsiveness in gastric cancer. CXCL13+CD8+T cells were associated with immunoevasive contexture with increased regulatory T (Treg) cells and dysfunctional cytotoxic T lymphocytes (CTLs). Moreover, the combinational analysis of CXCL13+CD8+ T cells and CD8+ T cells infiltration stratified patients into distinct risk groups with different clinical outcomes and chemotherapeutic responsiveness. Conclusively, intratumoral CXCL13+CD8+ T cells infiltration could be an independent prognostic and predictive marker for gastric cancer patients. CXCL13+CD8+ T cells represented an exhausted CD8+ T cell subset, and might be a potential immunotherapeutic target in gastric cancer.Concurrent blockade of different checkpoint receptors, notably PD-1 and CTLA-4, elicits greater anti-tumor activity for some tumor types, and the combination of different checkpoint receptor inhibitors is an active area of clinical research. We have previously demonstrated that anti-tumor vaccination, by activating CD8 + T cells, increases the expression of PD-1, CTLA-4, LAG-3 and other inhibitory receptors, and the anti-tumor efficacy of vaccination can be increased with checkpoint blockade. In the current study, we sought to determine whether anti-tumor vaccination might be further improved with combined checkpoint blockade. Using an OVA-expressing mouse tumor model, we found that CD8 + T cells activated in the presence of professional antigen presenting cells (APC) expressed multiple checkpoint receptors; however, T cells activated without APCs expressed LAG-3 alone, suggesting that LAG-3 might be a preferred target in combination with vaccination. Using three different murine tumor models, and peptide or DNA vaccines targeting three tumor antigens, we assessed the effects of vaccines with blockade of PD-1 and/or LAG-3 on tumor growth.
