Ferritin heavy chain supports stability and function of the regulatory T cell lineage.

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten-eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation.

IL-7 Receptor Drives Early T Lineage Progenitor Expansion.

IL-7 and IL-7R are essential for T lymphocyte differentiation by driving proliferation and survival of specific developmental stages. Although early T lineage progenitors (ETPs), the most immature thymocyte population known, have a history of IL-7R expression, it is unclear whether IL-7R is required at this stage. In this study, we show that mice lacking IL-7 or IL-7R have a marked loss of ETPs that results mostly from a cell-autonomous defect in proliferation and survival, although no changes were detected in Bcl2 protein levels. Furthermore, a fraction of ETPs responded to IL-7 stimulation ex vivo by phosphorylating Stat5, and IL-7R was enriched in the most immature Flt3+Ccr9+ ETPs. Consistently, IL-7 promoted the expansion of Flt3+ but not Flt3- ETPs on OP9-DLL4 cocultures, without affecting differentiation at either stage. Taken together, our data show that IL-7/IL-7R is necessary following thymus seeding by promoting proliferation and survival of the most immature thymocytes.

Cell competition in hematopoietic cells: Quality control in homeostasis and its role in leukemia.

Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. In the thymus, cell competition was addressed in thymus transplantation experiments, and found to be a homeostatic process that contributes to thymus turnover. Cell competition in the thymus depends on the capacity of T lymphocyte precursors to respond to interleukin 7 (IL-7). Failed cell competition permitted thymocyte self-renewal and autonomous thymopoiesis for several weeks, that culminated with leukemia onset. Beyond the work addressing cell competition in these cells, we discuss current hypotheses and observations that could be explained by cell competition. These include the clonal dynamics of hematopoietic stem cells in the ageing organism and initiation of leukemia.

Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iNKT) differentiation in mice.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the endogenous locus by CRISPR/Cas9 and tested the requirement of Ppic in hematopoiesis. Several immune cell lineages covering BM progenitors, lymphocyte precursors, as well as mature cells at the periphery were analyzed. While most lineages were unaffected, invariant NKT (iNKT) cells were reduced in percentage and absolute cell numbers in the Ppic-deficient thymus. This affected the most mature stages in the thymus, S2 and S3, and the phenotype was maintained at the periphery. Additionally, immature transitional T1 and T2 B lymphocytes were increased in the Ppic-deficient spleen, but the phenotype was lost in mature B lymphocytes. In sum, our data show that Ppic is dispensable for myeloid cells, platelets, erythrocytes, αß, and γδ T lymphocytes in vivo in the steady state, while being involved in B- and iNKT cell differentiation.

The mediating role of life satisfaction in the relationship between depression, anxiety, stress and burnout among Portuguese nurses during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic had a large consequence on healthcare systems, increasing the risks of psychological issues in health professionals. Nurses, in particular, have been exposed to multiple psychosocial stressors and struggled with intensive work, insufficiency of resources and uncertainty in the face of an unknown disease. Life satisfaction might protect nurses from the consequences of chronic stress. The aim of this study was to explore the mediating role of satisfaction with life in the relationship between depression, stress, anxiety and burnout (personal, work-related, and client-related). METHODS: A cross-sectional, descriptive, correlational study design was performed, using an online questionnaire distributed via social networks. A total of 379 nurses completed the survey, comprising standardized measures of satisfaction with life, resilience (Resilience Scale), depression, anxiety, stress (Depression Anxiety Stress Scales), and burnout (Copenhagen Burnout Inventory Scale). A hierarchical regression model was estimated for each burnout dimension. RESULTS: Participants showed high levels of work, personal and client-related burnout, 57.3%, 57%, and 35.1%, respectively. More than 70% of the respondents had a normal level of depressive symptoms, 66.8% presented normal level of anxiety and 33.5% of the respondents reported mild, moderate, severe or extremely severe symptoms of stress. The results revealed that life satisfaction partially mediated the association between stress and personal burnout, depression and work-related burnout, and the association between anxiety and client-related burnout in nurses. CONCLUSIONS: The COVID-19 pandemic brought added difficulties for nurses' work conditions, whereby it became necessary to develop adaptative measures that reduce stressors in work environment and promote nurses' life satisfaction.

T Cell Acute Lymphoblastic Leukemia as a Consequence of Thymus Autonomy.

Thymus autonomy is the capacity of the thymus to maintain T lymphocyte development and export independently of bone marrow contribution. Prolonging thymus autonomy was shown to be permissive to the development of T cell acute lymphoblastic leukemia (T-ALL), similar to the human disease. In this study, performing thymus transplantation experiments in mice, we report that thymus autonomy can occur in several experimental conditions, and all are permissive to T-ALL. We show that wild type thymi maintain their function of T lymphocyte production upon transplantation into recipients with several genotypes (and corresponding phenotypic differences), i.e., Rag2 - / - γc - / -, γc - / -, Rag2 - / - IL-7rα - / -, and IL-7rα - / - We found that the cellularity of the thymus grafts is influenced exclusively by the genotype of the host, i.e., IL-7rα-/- versus γc -/- Nonetheless, the difference in cellularity detected in thymus autonomy bore no impact on onset, incidence, immunophenotype, or pathologic condition of T-ALL. In all tested conditions, T-ALL reached an incidence of 80%, demonstrating that thymus autonomy bears a high risk of leukemia. We also analyzed the microbiota composition of the recipients and their genetic background, but none of the differences found influenced the development of T-ALL. Taken together, our data support that IL-7 drives cellular turnover non-cell autonomously, which is required for prevention of T-ALL. We found no influence for T-ALL in the specific combination of the genotypic mutations tested (including the developmental block caused by Rag deficiency), in microbiota composition, or minor differences in the genetic background of the strains.

The Teaching of Ethics and the Moral Competence of Medical and Nursing Students.

In a time marked by the development of innovative treatments in healthcare and the need for health professionals to deal with resulting ethical dilemmas in clinical practice, this study was developed to determine the influence of the bioethics teaching on the moral competence of medical and nursing students. The authors conduct a longitudinal study using the Moral Competence Test extended version before and after attending the ethics curricular unit, in three nursing schools and three medical schools of Portugal. In this questionnaire the participant is confronted with three ethical dilemmas (related to theft, euthanasia and the torture of a terrorist) and asked to evaluate arguments for and against the attitude of the main character (Worker, doctor and judge). For both nursing and medical students, C-score was lower after the attendance of the ethics curricular units, with a statistically significant decrease in the total score (from 21 to 19.5 on average; p = 0.046) for nursing students and a decrease not statistically significant for medical students (from 23.2 to 22 on average; p = 0.358). A multivariate analysis did not find any association between this decrease and gender, course, or age. The phenomenon of moral segmentation was observed, with better performance in the worker and judge dilemma, than in the doctor dilemma. These results highlight the need to reflect on the curricular strategies that can be implemented for health professionals to better develop moral competence and decision-making, allowing for the provision of humanized health care.

Seasonal differences in seminal plasma proteins from two bovine breeds adapted to a subtropical climate.

This study was designed to evaluate the seasonal expression of seminal plasma proteins from two bovine breeds adapted to a subtropical climate and their associations with post-thawing sperm and environmental characteristics. Semen samples were obtained three times in summer and three times in winter from four Crioulo Lageano and four Angus bulls. Seminal plasma was obtained by centrifugation, and the other portion of the semen was cryopreserved. Seminal plasma proteins were identified by 2D-nanoUPLC-MSE. Post-thawing assessments of sperm kinetics, morphology and membrane integrity were performed. Environmental data such as air temperature, air humidity and black globe temperature (BGT) were recorded, and the temperature-humidity index (THI) was calculated in summer and winter. Results showed that the climate varied significantly between seasons. Although no statistical differences were observed in semen quality between breeds, the protein profiles varied within and between seasons. We suggest that the most critical proteins in summer affecting sperm characteristics were TIMP-2, DNase, Clusterin, CFAH and GPx6. TIMP-2 and DNase showed a higher abundance in Crioulo Lageano in comparison with Angus, while Clusterin, CFAH and GPx6 presented a lower abundance. To the best of our knowledge, this is the first report of a recently evolved type of glutathione peroxidase, GPx6, in seminal plasma of bovines. In winter, five proteins were considered to be more critical: BSP1, BSP3, CCL2, Sulfhydryl oxidase and TIMP-2. BSP1 and TIMP-2 showed a lower abundance while BSP3, CCL2 and Sulfhydryl oxidase presented a higher abundance in this season in Crioulo Lageano in comparison with Angus.

RESUMO: Este estudo foi desenvolvido para avaliar a expressão sazonal de proteínas plasmáticas seminais de duas raças bovinas adaptadas ao clima subtropical e suas associações com espermatozóides pós-descongelamento e características ambientais. Amostras de sêmen foram obtidas três vezes no verão e três no inverno de quatro touros Crioulo Lageano e quatro Angus. O plasma seminal foi obtido por centrifugação e outra porção do sêmen foi criopreservada. As proteínas plasmáticas seminais foram identificadas por 2D-nanoUPLC-MSE. Foram realizadas avaliações pós-descongelamento da cinética espermática, morfologia e integridade da membrana. Dados ambientais como temperatura do ar, umidade do ar e temperatura do globo negro (BGT) foram registrados, e o índice temperatura-umidade (THI) foi calculado no verão e no inverno. Os resultados mostraram que o clima variou significativamente entre as estações. Embora não tenham sido observadas diferenças estatísticas na qualidade do sêmen entre as raças, os perfis proteicos variaram dentro e entre as estações. Sugerimos que as proteínas mais críticas no verão que afetam as características espermáticas foram TIMP-2, DNase, Clusterin, CFAH e GPx6. TIMP-2 e DNase apresentaram maior abundância em Crioulo Lageano em comparação com Angus, enquanto Clusterin, CFAH e GPx6 apresentaram menor abundância. Até onde sabemos, este é o primeiro relato de um tipo recentemente desenvolvido de glutationa peroxidase, GPx6, no plasma seminal de bovinos. No inverno, cinco proteínas foram consideradas mais críticas: BSP1, BSP3, CCL2, sulfidril oxidase e TIMP-2. BSP1 e TIMP-2 apresentaram menor abundância, enquanto BSP3, CCL2 e Sulfidril oxidase apresentaram maior abundância nesta temporada em Crioulo Lageano em comparação com Angus.

Cell competition is a tumour suppressor mechanism in the thymus.

Cell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between 'young' bone-marrow-derived and 'old' thymus-resident progenitors that, although genetically identical, execute differential gene expression programs. Disruption of cell competition leads to progenitor self-renewal, upregulation of Hmga1, transformation, and T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in pathology, genomic lesions, leukaemia-associated transcripts, and activating mutations in Notch1. Hence, cell competition is a tumour suppressor mechanism in the thymus. Failure to select fit progenitors through cell competition may explain leukaemia in X-linked severe combined immune deficiency patients who showed thymus-autonomous T-cell development after therapy with gene-corrected autologous progenitors.

Burnout among Portuguese healthcare workers during the COVID-19 pandemic.

BACKGROUND: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. METHODS: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. RESULTS: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. CONCLUSIONS: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.

Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients.

BACKGROUND: Endocrine therapy reduces breast cancer mortality by 40%, but resistance remains a major clinical problem. In this study, we sought to investigate the impact of aromatase inhibitor (AI) therapy on gene expression and identify gene modules representing key biological pathways that relate to early AI therapy resistance. METHODS: Global gene expression was measured on pairs of core-cut biopsies taken at baseline and at surgery from 254 patients with ER-positive primary breast cancer randomised to receive 2-week presurgical AI (n = 198) or no presurgical treatment (control n = 56) from the POETIC trial. Data from the AI group was adjusted to eliminate artefactual process-related changes identified in the control group. The response was assessed by changes in the proliferation marker, Ki67. RESULTS: High baseline ESR1 expression associated with better AI response in HER2+ tumours but not HER2- tumours. In HER2- tumours, baseline expression of 48 genes associated with poor antiproliferative response (p < 0.005) including PERP and YWHAQ, the two most significant, and the transcription co-regulators (SAP130, HDAC4, and NCOA7) which were among the top 16 most significant. Baseline gene signature scores measuring cell proliferation, growth factor signalling (ERBB2-GS, RET/GDNF-GS, and IGF-1-GS), and immune activity (STAT1-GS) were significantly higher in poor AI responders. Two weeks of AI caused downregulation of genes involved in cell proliferation and ER signalling, as expected. Signature scores of E2F activation and TP53 dysfunction after 2-week AI were associated with poor AI response in both HER2- and HER2+ patients. CONCLUSIONS: There is a high degree of heterogeneity in adaptive mechanisms after as little as 2-week AI therapy; however, all appear to converge on cell cycle regulation. Our data support the evaluation of whether an E2F signatures after short-term exposure to AI may identify those patients most likely to benefit from the early addition of CDK4/6 inhibitors. TRIAL REGISTRATION: ISRCTN, ISRCTN63882543, registered on 18 December 2007.

Effects of transcutaneous electrical nerve stimulation on the salivary flow of patients with hyposalivation induced by radiotherapy in the head and neck region-A randomised clinical trial.

Hyposalivation is a frequent complication after treatment with radiotherapy. To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) on the hyposalivation assessed through stimulated salivary flow (SSF). In this clinical trial, 68 patients (with hyposalivation) were randomly assigned to control (n = 31) or TENS (n = 37) group. Participants in control group received habitual care, while those in TENS group received 8 sessions (20 minutes each) delivered twice a week for four weeks. The electrodes were attached over the skin covering the salivary glands. The electric pulse was adjusted at a frequency of 50 Hz, pulse width of 250 µs and as intense as tolerated. SSF was evaluated through sialometry. Self-perception of salivary flow (SPSF) and quality of life (QL) was evaluated prior to, during and at 1, 3 and 6 months after treatment. Although no changes were observed in the control group for SSF at any timepoints, TENS group showed a progressive increase in SSF from the third session until the end of the treatment. Significant improvements were also found in SPSF, especially when the SSF reached values ≥0.7 mL/minute. The most expressive results were evident at 6 months after treatment so that SSF, SPSF and QL remained significantly higher (F = 9.5, P = 0.0001; H = 143.77, P < 0.0001; χ2  = 9.162, P = 0.02, respectively). TENS was effective at improving hyposalivation. The benefits on SSF, SPSF and QL give base to a promising therapeutic strategy for patients with hyposalivation after radiotherapy treating head and neck cancer.

Foxn1 Protein Expression in the Developing, Aging, and Regenerating Thymus.

The forkhead box N1 (Foxn1) protein is the key regulator of thymic epithelial cell (TEC) development, yet how Foxn1 functions remains largely unknown. All mature TECs arise from Foxn1-expressing progenitors/immature TECs and it is widely assumed that TECs as a whole are defined by Foxn1 expression. However, data on the Foxn1 protein are virtually lacking. In this study, we developed novel tools to visualize Foxn1 protein expression at single-cell resolution. We generated Foxn1 knock-in mice expressing a C-terminal hemagglutinin-tagged Foxn1 protein, and a cytometry-grade monoclonal anti-Foxn1 Ab. We evaluated Foxn1 expression patterns in TEC subsets and its dynamics during normal thymus development, aging, injury, and regeneration. Upon challenges, upregulation of Foxn1 was a common feature of thymus regeneration, but the timing of Foxn1 expression changed and the responding TEC subsets depended on the type of treatment. Whereas dexamethasone and recombinant human fibroblast growth factor 7 promoted expansion of Foxn1(+)Ly51(+)CD80(-) TECs, castration led to expansion of Foxn1(+)Ly51(-)CD80(+) TECs. Collectively, Foxn1 expression is highly heterogeneous in the normal thymus, with large fractions of Foxn1(low) or Foxn1(-) TECs accumulating with age. Furthermore, Foxn1 expression is responsive to perturbations.

Electrical Stimulation for Treatment of Dysphagia Post Head Neck Cancer: A Systematic Review and Meta-Analysis.

Introduction Dysphagia induced by radiotherapy in the head and neck region comprises a challenging scenario and sometimes difficult rehabilitation due to the severity of the adverse effects. Some resources such as electrical stimulation have emerged as an alternative to complement the therapeutic process, but there is still no consensus on its use. Objective The purpose of the present study was to evaluate, through a meta-analysis, the effect of electrical stimulation on the rehabilitation of dysphagia generated after head and neck cancer treatment. Data Synthesis Four randomized controlled trials with a total of 146 participants were included. The age of the participants was 58.37 ± 1.8 years old and there was a predominance of males. The time to start the intervention ranged from 50.96 ± 40.12 months after cancer treatment. The intervention showed great heterogeneity regarding the positioning of the electrodes, parameters, duration of the stimulus, number of sessions, and intensity. No difference was identified in the following aspects: oral transit time, hyoid elevation, penetration and/or aspiration after electrostimulation. The quality of the evidence ranged from very low to moderate and high risk of bias. Conclusion In this meta-analysis, we found weak evidence for small and moderate swallowing benefits in patients after radiotherapy for head and neck cancer in short-term clinical trials.

Matrix metalloproteinases and epidermal wound repair.

Epidermal wound healing is a complex and highly coordinated process where several different cell types and molecules, such as growth factors and extracellular matrix (ECM) components, play an important role. Among the many proteins that are essential for the restoration of tissue integrity is the metalloproteinase (MMP) family. MMPs can act on ECM and non-ECM components affecting degradation and modulation of the ECM, growth-factor activation and cell-cell and cell-matrix signalling. MMPs are secreted by different cell types such as keratinocytes, fibroblasts and inflammatory cells at different stages and locations during wound healing, thereby regulating this process in a very coordinated and controlled way. In this article, we review the role of MMPs and their inhibitors (TIMPs), as well as the disintegrin and metalloproteinase with the thrombospondin motifs (ADAMs) family, in epithelial wound repair.

Influence of excessive daytime sleepiness on the treatment adherence of obstructive sleep apnea.

OBJECTIVES: To compare positive airway pressure (PAP) adherence between patients with or without excessive daytime sleepiness (EDS) in mild, moderate and severe obstructive sleep apnea (OSA). METHODS: Patients ≥18 years diagnosed with OSA in 2018 and 2019, without previous history of PAP usage and with adherence registration in the first medical consultation after treatment initiation, were included. EDS was defined as a score of ≥10 on the Epworth Scale. Patients were divided into two groups according to the adherence to PAP: "Adherent" if using the device for ≥4 h for ≥70% of the nights and "Nonadherent" otherwise. Simple and multiple logistic regression models for adherence were determined. RESULTS: 321 patients were included, most male (64.2%), with mean age 56.56 years. Most patients had severe OSA (n = 159; 49.5%), and median AHI was 29.3/h [16.8; 47.5]. Being older or having a severe OSA resulted in an increased adherence (OR = 1.020, CI95% = [1.002; 1.039] and OR = 2.299, CI95% = [1.273; 4.191], respectively). In patients without EDS a statistically significant difference was found in adherence between those with severe OSA and both mild and moderate OSA categories (OR = 0.285, p = 0.023 and OR = 0.387, p = 0.026, respectively), with patients with severe OSA being adherent. There was no statistical difference in adherence between patients with or without EDS (OR 1.083; p = 0.876), nor in the different degrees of severity in those with EDS. CONCLUSION: In our study there were no differences in PAP therapy adherence between patients with or without excessive daytime sleepiness. Older age and higher OSA severity resulted in higher adherence rates.

Preventive measures for the progression of dysphagia in patients with cancer of head and neck subjected to radiotherapy: a systematic review with meta-analysis. / Medidas de prevenção da progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia: uma revisão sistemática com meta-análise.

PURPOSE: To identify the effects of prophylactic, non-pharmacological measures on the progression of dysphagia in patients with head and neck cancer undergoing radiotherapy. RESEARCH STRATEGIES: The search was performed in Medline (via PubMed), Scopus, and Embase databases, as well as in the gray literature. SELECTION CRITERIA: Randomized clinical trials were included, with adult patients (≥ 18 years old) and diagnosed with head and neck cancer, treated with radiotherapy (with or without surgery and chemotherapy), and submitted to non-pharmacological protocols for the prevention of dysphagia. DATA ANALYSIS: The risk of bias was assessed using the PEDRO scale and the overall quality of evidence was assessed using the GRADE instrument. RESULTS: Four studies were considered eligible, and of these, two were included in the meta-analysis. The result favored the intervention group, with a mean difference of 1.27 [95% CI: 0.74 to 1.80]. There was low heterogeneity and the mean score for risk of bias was 7.5 out of 11 points. The lack of detail in the care with selection, performance, detection, attrition, and reporting biases contributed to the judgment of the quality of the evidence, considered low. CONCLUSION: Prophylactic measures to contain dysphagia can promote important benefits on the oral intake of patients with head and neck cancer when compared to those who did not undergo such a therapeutic measure during radiotherapy.

OBJETIVO: Identificar os efeitos de medidas profiláticas, não farmacológicas, sobre a progressão da disfagia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia. ESTRATÉGIA DE PESQUISA: A busca foi realizada nas bases de dados Medline (via PubMed), Scopus e Embase, assim como na literatura cinzenta. CRITÉRIOS DE SELEçÃO: Foram incluídos ensaios clínicos randomizados, com pacientes adultos (≥ 18 anos) e diagnóstico de câncer de cabeça e pescoço, tratados com radioterapia (associada ou não à cirurgia e quimioterapia) submetidos a protocolos não farmacológicos de prevenção da disfagia. ANÁLISE DOS DADOS: O risco de viés foi avaliado por meio da escala PEDRO e a qualidade global da evidência foi avaliada de acordo com o instrumento GRADE. RESULTADOS: Foram considerados elegíveis 4 estudos, e desses, dois foram incluídos na metanálise. O resultado favoreceu o grupo intervenção, com diferença média de 1,27 [IC 95%: 0,74 à 1,80]. Houve baixa heterogeneidade e a pontuação média para risco de viés foi de 7,5 de um total de 11 pontos. A falta de detalhamento nos cuidados com os vieses de seleção, performance, detecção, atrito e de relato contribuíram para o julgamento da qualidade da evidência, considerada baixa. CONCLUSÃO: Medidas profiláticas de contenção da disfagia podem promover importantes benefícios sobre a ingesta oral dos pacientes com câncer de cabeça e pescoço, quando comparados aqueles que não realizaram tal medida terapêutica ao longo da radioterapia.

A cross-sectional study in critically ill patients affected by COVID-19 in an intensive care unit: would Acinetobacter baumannii resistant to carbapenems be the biggest villain?

AIM: to describe cases of infection of Acinetobacter baumannii (A. baumannii) in critically ill patients affected by COVID-19, admitted to an intensive care unit (ICU), using dexamethasone. METHODOLOGY: cross-sectional study conducted on patients admitted to the intensive care unit COVID-19 survey among hospitalized patients from November 2020 to March 2021. SETTING: large hospital, reference for caring for patients with COVID-19 in Bahia (Brazil). PATIENTS: a convenience sample of 22 patients admitted to the COVID ICU signed the consent form agreeing to participate in the study. Three patients were excluded for having decided to participate without signing the form. RESULTS: of the 22 patients listed, 45 % (10) had blood infection or mechanical ventilation-associated pneumonia by A. baumannii in blood cultures and/or tracheal aspirate secretion. We observed that there is a moderate correlation between the length of stay and infection by A. baumannii (Spearman's ρ; 0.592; p-value<0.005) and a strong correlation between the number of days on mechanical ventilation and infection by these bacteria (Spearman's ρ; 0.740; p-value<0.001). This percentage is higher than the value of 0.62 % of infection by A. baumannii in this ICU in the same period of the year before COVID-19 (p-value<0.0001). CONCLUSIONS: hospitals that receive patients with COVID-19 may be vulnerable to outbreaks of multi-drug resistant organisms, such as A. baumannii . It is worth reflecting on the care and operational practices in handling these patients, especially in isolation and restriction measures for those from other nosocomial areas.

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.