Performance of care for end‐of‐life cancer patients in Tuscany: The interplay between place of care, aggressive treatments, opioids, and place of death. A retrospective cohort study

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Association Between Alcohol Intake and Cardiac Remodeling

Background: Alcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial. Objectives: The authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up. Methods: Among the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes. Results: Among the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking. Conclusions: After 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.info:eu-repo/semantics/publishedVersio

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

Cytotoxic activity mediated by CD8+ T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of natural killer (NK) cell phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than age‐matched controls. The accumulation of circulating senescent NK cells (CD56dim CD57bright) correlated positively with skin lesion size in the same patients, suggesting that they, like circulating senescent CD8+ T cells, may contribute to the immunopathology of CL. However, this senescent population had lower cutaneous lymphocyte antigen expression and so had diminished skin‐homing potential compared with total or senescent CD8+ T cells. This was confirmed in CL skin lesions where we found a predominance of CD8+ T cells (both senescent and non‐senescent) that correlated with the severity of the disease. Although there was also a correlation between the proportions of senescent NK cells (CD56+ CD57+) in the skin and lesion size, this was less evident. Collectively our results demonstrate first‐hand that senescent cytotoxic cells may mediate skin pathology during human cutaneous leishmaniasis. However, as senescent cytotoxic CD8+ T cells predominate in the skin lesions, they may have a greater role than NK cells in mediating the non‐specific skin damage in CL

Comfort from the perspective of families of people hospitalized in the intensive care unit

This study aimed at understanding the meaning of comfort to the families of people in intensive care units. It consists of a qualitative study carried out in the intensive care unit of a hospital in Salvador-Bahia. Fourteen family members were interviewed. The authors utilized the theoretical principles of symbolic interactionism and the technique of qualitative data analysis. Results indicated that the categories Safety, Receptiveness, Information, Proximity, Social and Spiritual Support, Convenience and Integration expressed the meaning of comfort, which was comprised of reliability in terms of technical-scientific competence and a supportive and sensitive attitude of the team, chance of recovery, access to information and the opportunity to be close to the patient, support of people in their social life, spiritual sources and the environmental structure of the hospital, preservation of self-care and routine activities. It was concluded that the family is important as objects and subjects of the actions in healthcare and must be the focus in public health policies and programs in Brazil

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4^{+} and CD8^{+} T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1^{+}, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8^{+}CD45RA^{+}CD27^{-} T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis

Placenta microstructure and microcirculation imaging with diffusion MRI

PURPOSE: To assess which microstructural models best explain the diffusion-weighted MRI signal in the human placenta. METHODS: The placentas of nine healthy pregnant subjects were scanned with a multishell, multidirectional diffusion protocol at 3T. A range of multicompartment biophysical models were fit to the data, and ranked using the Bayesian information criterion. RESULTS: Anisotropic extensions to the intravoxel incoherent motion model, which consider the effect of coherent orientation in both microvascular structure and tissue microstructure, consistently had the lowest Bayesian information criterion values. Model parameter maps and model selection results were consistent with the physiology of the placenta and surrounding tissue. CONCLUSION: Anisotropic intravoxel incoherent motion models explain the placental diffusion signal better than apparent diffusion coefficient, intravoxel incoherent motion, and diffusion tensor models, in information theoretic terms, when using this protocol. Future work will aim to determine if model-derived parameters are sensitive to placental pathologies associated with disorders, such as fetal growth restriction and early-onset pre-eclampsia