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Cancer Cell Jan 2024Over the last decade, the composition of the gut microbiota has been found to correlate with the outcomes of cancer patients treated with immunotherapy. Accumulating... (Review)
Review
Over the last decade, the composition of the gut microbiota has been found to correlate with the outcomes of cancer patients treated with immunotherapy. Accumulating evidence points to the various mechanisms by which intestinal bacteria act on distal tumors and how to harness this complex ecosystem to circumvent primary resistance to immune checkpoint inhibitors. Here, we review the state of the microbiota field in the context of melanoma, the recent breakthroughs in defining microbial modes of action, and how to modulate the microbiota to enhance response to cancer immunotherapy. The host-microbe interaction may be deciphered by the use of "omics" technologies, and will guide patient stratification and the development of microbiota-centered interventions. Efforts needed to advance the field and current gaps of knowledge are also discussed.
Topics: Humans; Melanoma; Microbiota; Gastrointestinal Microbiome; Neoplasms; Immunotherapy; Host Microbial Interactions
PubMed: 38157864
DOI: 10.1016/j.ccell.2023.12.003 -
CMAJ : Canadian Medical Association... Nov 2023
Topics: Humans; Nuclear Family; Spouses; Patients; Delirium
PubMed: 37984931
DOI: 10.1503/cmaj.230833-f -
Kidney360 Jul 2023Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients...
KEY POINTS
Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.
BACKGROUND
Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.
METHODS
We conducted a genome-wide association study in 1369 participants in the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI Study; a multiethnic population of hospitalized participants with and without AKI matched on demographics, comorbidities, and kidney function before hospitalization. We then completed functional annotation of top-performing variants for AKI using single-cell RNA sequencing data from kidney biopsies in 12 patients with AKI and 18 healthy living donors from the Kidney Precision Medicine Project.
RESULTS
No genome-wide significant associations with AKI risk were found in Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (). The top two variants with the strongest association with AKI mapped to the gene and gene locus, rs17538288 (odds ratio, 1.55; 95% confidence interval, 1.32 to 182; ) and rs7546189 (odds ratio, 1.53; 95% confidence interval, 1.30 to 1.81; ). In comparison with kidney tissue from healthy living donors, kidney biopsies in patients with AKI showed differential expression in proximal tubular epithelial cells (adjusted = 3.910) and thick ascending limb of the loop of Henle (adjusted = 8.710) and differential gene expression in thick ascending limb of the loop of Henle (adjusted = 4.910).
CONCLUSIONS
AKI is a heterogeneous clinical syndrome with various underlying risk factors, etiologies, and pathophysiology that may limit the identification of genetic variants. Although no variants reached genome-wide significance, we report two variants in the intergenic region between and , suggesting this region as a novel risk for AKI susceptibility.
Topics: Humans; Genome-Wide Association Study; Acute Kidney Injury
PubMed: 37273234
DOI: 10.34067/KID.0000000000000175 -
Ultraschall in Der Medizin (Stuttgart,... Dec 2023The CME review is intended to explain and discuss the clinical value of lung ultrasound but also to enable a pragmatically oriented approach by analyzing the clinical...
The CME review is intended to explain and discuss the clinical value of lung ultrasound but also to enable a pragmatically oriented approach by analyzing the clinical aspect. This includes knowledge of the pre-test probability, the acuteness of the disease, the current clinical situation, detection and/or characterization, initial diagnosis or follow up assessment and the peculiarities of exclusion diagnosis. Diseases of the pleura and lungs are described using these criteria with their direct and indirect sonographic signs and the specific clinical significance of ultrasound findings. The importance and criteria of conventional B-mode, color Doppler ultrasound with or without spectral analysis of the Doppler signal and contrast-enhanced ultrasound are discussed as well.
Topics: Humans; Lung; Ultrasonography; Pleura; Ultrasonography, Doppler, Color; Thorax
PubMed: 37054729
DOI: 10.1055/a-2010-7282 -
Science Translational Medicine Jul 2023T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly...
T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.
Topics: Humans; Mice; Animals; T-Lymphocytes; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Receptors, Antigen, T-Cell
PubMed: 37494469
DOI: 10.1126/scitranslmed.abq0476 -
Frontiers in Immunology 2023The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies... (Review)
Review
The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies using chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. The great success in the context of hematologic malignancies has made especially CAR T cell therapy a promising approach capable of achieving long-lasting remission. However, the causalities involved in mediating resistance to treatment or relapse are still barely investigated. Research on T cell exhaustion and dysfunction has drawn attention to host-derived factors that define both the immune and tumor microenvironment (TME) crucially influencing efficacy and toxicity of cellular immunotherapy. The microbiome, as one of the most complex host factors, has become a central topic of investigations due to its ability to impact on health and disease. Recent findings support the hypothesis that commensal bacteria and particularly microbiota-derived metabolites educate and modulate host immunity and TME, thereby contributing to the response to cancer immunotherapy. Hence, the composition of microbial strains as well as their soluble messengers are considered to have predictive value regarding CAR T cell efficacy and toxicity. The diversity of mechanisms underlying both beneficial and detrimental effects of microbiota comprise various epigenetic, metabolic and signaling-related pathways that have the potential to be exploited for the improvement of CAR T cell function. In this review, we will discuss the recent findings in the field of microbiome-cancer interaction, especially with respect to new trajectories that commensal factors can offer to advance cellular immunotherapy.
Topics: Humans; T-Lymphocytes; Neoplasm Recurrence, Local; Receptors, Chimeric Antigen; Immunotherapy; Microbiota; Tumor Microenvironment
PubMed: 37799719
DOI: 10.3389/fimmu.2023.1269015 -
Communications Biology Nov 2023Spouses may affect each other's sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for...
Spouses may affect each other's sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r = 0.11; 95% CI = 0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r = -0.11; -0.12, -0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r = 0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r = 0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (-0.15; -0.26, -0.04) and snoring (-0.15; -0.27, -0.04). Findings support the notion that an individual's sleep may impact that of their partner, promoting opportunities for sleep interventions at the family-level.
Topics: Humans; Chronotype; Circadian Rhythm; Sleep; Sleep Duration; Spouses; Male; Female; Mendelian Randomization Analysis
PubMed: 37957254
DOI: 10.1038/s42003-023-05521-7 -
Ultraschall in Der Medizin (Stuttgart,... Oct 2023Ultrasonography of intracranial arteries is a non-invasive and highly efficient method for the diagnosis and follow-up of patients with cerebrovascular diseases, also in... (Review)
Review
Ultrasonography of intracranial arteries is a non-invasive and highly efficient method for the diagnosis and follow-up of patients with cerebrovascular diseases, also in the bedside setting of the critically ill. For reliable assessment and interpretation of sonographic findings, the technique requires - apart from dedicated anatomic and pathophysiological knowledge of cerebral arteries and their hemodynamics - the comprehension of alternative imaging modalities such as CT or MR angiography. This article reviews the transcranial color-coded duplex sonographic (TCCS) examination technique including the transcranial Doppler sonography (TCD) for a standardized ultrasound assessment of the intracranial arteries and typical pathological cases. As a complementary tool, transorbital ultrasound for the assessment of the optic nerve sheath diameter and adjacent structures is also described in this article.
Topics: Humans; Cerebrovascular Disorders; Ultrasonography, Doppler, Transcranial; Ultrasonography, Doppler, Duplex; Cerebrovascular Circulation; Arteries; Brain; Ultrasonography, Doppler, Color
PubMed: 37832531
DOI: 10.1055/a-2103-4981 -
Kidney360 Jan 2024Sex differences in AKI continue to be identified. Generally, women are protected from AKI when compared to men. Much of the protection exhibited in women is diminished... (Review)
Review
Sex differences in AKI continue to be identified. Generally, women are protected from AKI when compared to men. Much of the protection exhibited in women is diminished after menopause. These sex and age effects have also been noted in animal models of AKI. Gonadal hormones, as modifiers of incidence, severity, and progression of AKI, have been offered as likely contributors to this sex and age effect. In animal models of AKI, estrogen and testosterone seem to modulate susceptibility. Questions remain however regarding cellular and molecular changes that are initiated by modulation of these hormones because both estrogen and testosterone have effects across cell types that play a role in AKI. Although findings have largely been informed by studies in males, molecular pathways that are involved in the initiation and progression of AKI may be modulated by gonadal hormones. Compounding the hormone-receptor effects are developmental effects of sex chromosomal complement and epigenetic influences that may confer sex-based baseline differences in gene and protein expression, and gene dosage effects of X inactivation and escape on molecular pathways. Elucidation of sex-based protection may afford a more complete view of AKI and potential therapeutic interventions. Furthermore, the effect on susceptibility to AKI in transgender patients, who receive life-altering and essential gender-affirming hormone therapy, requires greater attention. In this review, several potential contributors to the sex differences observed in humans and animal models are discussed.
Topics: Animals; Humans; Male; Female; Sex Characteristics; Sex Factors; Acute Kidney Injury; Testosterone; Estrogens
PubMed: 37990360
DOI: 10.34067/KID.0000000000000321 -
Revista Brasileira de Enfermagem 2023to assess the burden of spouse and non-spouse caregivers of older adults with stroke-induced-dependency after discharge from a university hospital's Specialized Care...
OBJECTIVE
to assess the burden of spouse and non-spouse caregivers of older adults with stroke-induced-dependency after discharge from a university hospital's Specialized Care Stroke Unit in southern Brazil.
METHODS
a longitudinal survey. The sample consisted of 48 consenting caregivers, among which 20 were spouse caregivers. Data were collected between May 2016 and July 2018. One week after discharge, caregivers completed a sociodemographic profile, the Functional Independence Measure, and the Caregiver Burden Scale. Burden was also measured two months after discharge. Data were analyzed using Multivariate Analyses of Variance.
RESULTS
regarding time 1, non-spouse caregivers experienced greater burden with respect to social isolation (p = .01). Along with a persistently greater sense of isolation (p=.04), non-spouse caregivers felt far greater general strain (p =.01).
CONCLUSION
statistically significant differences in burden over time highlight the importance of assessing caregiver burden after discharge and the need for a formal support program.
Topics: Humans; Aged; Caregivers; Spouses; Longitudinal Studies; Stroke; Emotions
PubMed: 38055489
DOI: 10.1590/0034-7167-2023-0052