TGF-ß blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.

HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of the anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirmed the latency reversal properties of in vivo TGF-ß blockade, decreased viral reservoirs and stimulated immune responses. Eight SIV-infected macaques on suppressive ART were treated with 4 2-week cycles of galunisertib. ART was discontinued 3 weeks after the last dose, and macaques euthanized 6 weeks after ART-interruption(ATI). One macaque did not rebound, while the remaining rebounded between week 2 and 6 post-ATI. Galunisertib led to viral reactivation as indicated by plasma viral load and immunoPET/CT with the 64Cu-DOTA-F(ab')2-p7D3-probe. Half to 1 Log decrease in cell-associated (CA-)SIV DNA was detected in lymph nodes, gut and PBMC, while intact pro-virus in PBMC decreased by 3-fold. No systemic increase in inflammatory cytokines was observed. High-dimensions cytometry, bulk and single-cell RNAseq revealed a shift toward an effector phenotype in T and NK cells. In summary, we demonstrated that galunisertib, a clinical stage TGFß inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity.

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference.

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.

Genotoxicity of Particles From Grinded Plastic Items in Caco-2 and HepG2 Cells.

Large plastic litters degrade in the environment to micro- and nanoplastics, which may then enter the food chain and lead to human exposure by ingestion. The present study explored ways to obtain nanoplastic particles from real-life food containers. The first set of experiments gave rise to polypropylene nanoplastic suspensions with a hydrodynamic particle size range between 100 and 600 nm, whereas the same grinding process of polyethylene terephthalate (PET) produced suspensions of particles with a primary size between 100 and 300 nm. The exposure did not cause cytotoxicity measured by the lactate dehydrogenase (LDH) and water soluble tetrazolium 1 (WST-1) assays in Caco-2 and HepG2 cells. Nanoplastics of transparent PET food containers produced a modest concentration-dependent increase in DNA strand breaks, measured by the alkaline comet assay [net induction of 0.28 lesions/106 bp at the highest concentration (95% CI: 0.04; 0.51 lesions/106 base pair)]. The exposure to nanoplastics from transparent polypropylene food containers was also positively associated with DNA strand breaks [i.e., net induction of 0.10 lesions/106 base pair (95% CI: -0.04; 0.23 lesions/106 base pair)] at the highest concentration. Nanoplastics from grinding of black colored PET food containers demonstrated no effect on HepG2 and Caco-2 cells in terms of cytotoxicity, reactive oxygen species production or changes in cell cycle distribution. The net induction of DNA strand breaks was 0.43 lesions/106 bp (95% CI: 0.09; 0.78 lesions/106 bp) at the highest concentration of nanoplastics from black PET food containers. Collectively, the results indicate that exposure to nanoplastics from real-life consumer products can cause genotoxicity in cell cultures.

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

Paediatric nursing management of renal replacement therapy: Intensive care nursing or dialysis nursing?

BACKGROUND: Children who develop Acute Kidney Injury may start renal replacement therapy (RRT) in Paediatric or Neonatal Intensive Care Units (hereafter PICU or NICU); RRT can be delivered either by paediatric dialysis nurses or by critical care nurses. In both case, nurses devoted to this task must have a high level of competence in providing care to children receiving haemodialytic treatment in a specific technological environment. AIM: The objective of this research was to investigate which models have been adopted to organize nursing care in RRT management in different Italian PICU and NICU, and to explore the training of ICU nurses on the management of RRT. METHODS: A multi-centre survey was conducted through an online questionnaire directed to the Italian PICU and NICU nurse coordinators. RESULTS: A total of 15 Intensive Care Units (12 PICU and 3 NICU) in 12 hospitals were involved. The mean nurse/patient ratio in these units is 1:3. In 72.7% of critical care units, dialysis treatment is delivered by critical care nurses belonging to the unit itself, while in 27.3% of units paediatric dialysis nurses are in charge of dialysis treatment in collaboration with critical care nurses. In 25% of surveyed units there is some structured form of collaboration between Paediatric Dialysis nurses and critical care nurses. However, 75% of units did not respond to this specific question. The different units adopt various forms of RRT training for nursing staff. CONCLUSION: The scenario resulting from this analysis showed how in our sample of Italian hospitals there is no standard practice for RRT nursing management. In addition, although various forms of training for nursing staff exist, a proper educational programme and/or a standardized specific training about RRT management for nursing staff is not in place in the surveyed hospitals. RELEVANCE TO CLINICAL PRACTICE: The lack of standardized protocols or guidelines for RRT delivery to critically ill children can compromise their safety. The structuring of these protocols and the production of best clinical practice guidelines would allow standardization of the nursing management of the RRT and of the corresponding training. This may help to provide the proper care and to guarantee the patients' safety.

Transition of care in pediatric oncohematology: a systematic literature review.

BACKGROUND: The transition of medical care from a pediatric to an adult environment is a psychological change, a new orientation that requires a self-redefinition of the individual, to understand that changes are taking place in his life. Up to 60 percent of pediatric patients who transition to adult services will experience one or more disease or treatment-related complication as they become adults. A nurse who knows how to recognize potential barriers at an early stage can play a pivotal role in the educational plan for the transition process. MATERIALS AND METHODS: A literature search was undertaken of PUBMED, CINAHL and The Cochrane Library, with specific inclusion and exclusion criteria, including articles published in the lasts ten years.This literature review has been performed according to the PRISMA statement. RESULTS: Using the keywords in different combination 38 articles were found in The Cochrane Library, 5877 in PUBMED, 274 in CINAHL. 88 articles were selected after the abstract screening. 31 after removing the duplicates and reading the full text. DISCUSSION: The main themes surrounding transition of care that emerged from the synthesis are the organization of care within common models of transition, innovative clinical approaches to transition, and the experience of patients and caregivers. The transition from pediatric to adult care of cancer or SCD survivors is an emerging topic in pediatric nursing. The organization of care is affected by the lack of clear and well-structured organizational models. Further research is needed to deepen the understanding of some aspects of the transition.

Transcatheter heart valve interventions: where are we? Where are we going?

Transcatheter heart valve interventions have transformed the outcomes of patients with valvular heart disease (VHD) who are unfavourable candidates for surgery. Technological advances have allowed extension of these interventions to younger or lower risk patients and those with other forms of VHD and may in the future permit earlier treatment of VHD in less symptomatic patients or those with moderate disease. The balance of risks and benefits is likely to differ between lower and higher risk patients, and more evidence is needed to evaluate the net benefit of transcatheter technology in these groups. As academic researchers, clinicians, industry, and patient stakeholders collaborate to research these broader indications for transcatheter valve interventions, it is essential to address (i) device durability and deliverability, (ii) specific anatomical needs (e.g. bicuspid aortic valves, aortic regurgitation, mitral and tricuspid valve disease), (iii) operator training, and (iv) the reinforced importance of the multidisciplinary Heart Team.

Rights of the Dying Child: The Nurses' Perception.

AIM: The Charter of the Rights of the Dying Child was formulated as a professional guide for caring the child in the final stages. The study examines the nurses' degree of agreement with the Charter's principles and their perception of the implementation of those principles in hospital. MATERIALS AND METHODS: A multicenter, cross-sectional study to observe the nurses' positions about the 10 rights outlined in the Charter, using an online questionnaire in 5 pediatric hospitals in northern Italy. RESULTS: A total of 119 nurses (44.9%) completed the questionnaire. The majority (range: 86.6-100%) expressed their agreement with the Charter's principles (Likert ≥4). Lower ratings were reported in Charter's principles implementation items (range: 42.9-89.1%). Being older and working in a smaller hospital lead the nurses to overlook the child's right to be informed and to be given the opportunity to make decisions about his/her own life and death (p = 0.02, p < 0.01). Postgraduate training induced greater awareness of the dying child (p = 0.01). CONCLUSIONS: This study highlights the value of the Charter of the Rights of the Dying Child as a reference guideline for nurses working in pediatric hospitals. Better training is important to improve the nurse's communication skills and the pediatric palliative care should be offered to all families that have a child with incurable disease mostly in the end of life.

A malignant cutaneous neuroendocrine tumor with features of Merkel cell carcinoma and differentiating neuroblastoma.

We report an unusual primary cutaneous neuroendocrine carcinoma that shows histologic and immunohistochemical features of ganglioneuroblastoma/differentiating neuroblastoma. The neoplasm is composed predominantly of small atypical neoplastic cells embedded in distinct clusters of immature and mature ganglion cells with associated neuropil. The neoplastic cells show strong perinuclear staining for cytokeratin 20 (CK20) with a dot-like pattern, supporting our contention that this is an unusual variant of Merkel cell carcinoma. To the best of our knowledge, ganglioneuroblastoma-like differentiation has not been previously described in Merkel cell carcinoma.