Development of a predictive score to discriminate community acquired pneumonia with underlying lung cancer: A retrospective case - control study.

BACKGROUND: A pneumonic infiltrate might hide an occult lung cancer (LC). This awareness depends on each clinician personal experience, turning definitive LC diagnosis challenging and possibly delayed. In this study we aimed to develop a clinical score to better identify those cases. MATERIALS AND METHODS: We conducted a retrospective case-control study, including previously undiagnosed LC patients admitted in our institution, with a presumptive suspicious of community acquired pneumonia (CAP). Cases were compared with random CAP inpatient controls, using a matched 2:1 ratio. Demographic, clinical, and laboratorial variables were assessed for a possible association with the presence of a CAP with underlying LC (CAP-uLC). RESULTS: Among 535 hospitalized LC patients, 43 cases had a presentation compatible with CAP and were compared with 86 CAP controls. A scoring system was built using 6 independent variables, which positively correlated with CAP-uLC: smoking history (OR: 8.3 [1.9-36.2]; p = 0.005); absence of fever (6.5 [2.0-21.5]; p = 0.002); sputum with blood (5.9 [1.2-29.9]; p = 0.033); platelet count ≥ 232x103/µL (5.8 [1.6-20.6]; p = 0.006); putative alternative diagnosis than CAP (4.6 [1.5-14.7]; p = 0.009); and duration of symptoms ≥ 10 days (3.7 [1.1-13.0]; p = 0.037). Our score presented an AUC of 0.910 (95 % CI, 0.852-0.967; p < 0.001), a sensitivity of 88.1 % and specificity of 84.7 %, in predicting the risk of presenting a CAP-uLC, when set to a cutoff of 18. CONCLUSION: We propose a novel risk score aimed to aid clinicians identifying patients with CAP-uLC in the acute setting, possibly prompting early LC diagnosis.

The knowledge of primary health care professionals regarding mental health: diagnosis by mhGAP.

OBJECTIVE: To analyze knowledge about priority topics in mental health care of strategic actors who work in regions where the Health Care Planning (PAS) methodology is used. METHODS: This is a quantitative, descriptive, cross-sectional, and observational study carried out with professionals from six health regions, distributed in three Brazilian states (Goiás, Rondônia and Maranhão) and linked to the project "Saúde mental na APS" (Mental health in PHC) of the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (Proadi-SUS - Institutional Development Support Program of the Brazilian Unified Health System). The sample was made up of professionals who participated in the intervention guide multiplier training stage for mental, neurological and alcohol and other drug use disorders in the primary health care network, from July to September 2022. Data collection was through a self-administered instrument, in electronic format, consisting of a block with socioeconomic items and a structured questionnaire to assess participants' knowledge about priority topics in mental health. Descriptive analyses and comparison of proportions were conducted to analyze the data. RESULTS: A total of 354 health professionals participated in the study. Regarding the percentage of correct answers in the questionnaire on priority topics in mental health, the highest medians were identified in the "Depression" module. On the other hand, the content referring to the modules "Essential care and practices" and "Other important complaints" presented the lowest values. Furthermore, some participant characteristics were found to be associated with the percentage of correct answers in the questionnaire modules. CONCLUSIONS: The findings reveal opportunities for improvement, mainly in knowledge related to communication skills and the approach to emotional and physical distress without diagnostic criteria for a specific disease, offering support for planning actions aimed at intensifying the consideration of these themes during the operational stages of PAS.

Brazilian Scale for Evaluation of Mental Health Care Needs: Additional Evidence.

OBJECTIVE: To investigate validity evidence of the Brazilian Scale for Evaluation of Mental Health Care Needs (CuidaSM). METHODS: This is a psychometric study, which seeks additional evidence of internal structure. Data collection was carried out in 11 Primary Health Care (PHC) services , which implement the Health Care Planning (HCP) methodology, distributed across the five Brazilian regions. The preliminary version of CuidaSM, containing a block self-referred by the user and another block evaluated by PHC professionals, was applied to users aged 18 or over who attended the PHC services for consultation with a higher education professional. The techniques of confirmatory factor analysis and network analysis were used to investigate validity evidence. For the primary data of the confirmatory factor analysis, the factorial loads and the item's predictive power (R2) were used. Six model adjustment indices were adopted and reliability was measured by three indicators using Bayesian estimation. RESULTS: A total of 879 users participated in the study. By confirmatory factor analysis, factorial loads ranged from 0.43 to 0.99 and R2 from 0.19 to 0.98. Both the primary indicators and the model adequacy indices were established at satisfactory and consistent levels. The network analysis showed that the items were appropriately associated with their peers, respecting the established dimensions, which again indicates the sustainability and stability of the proposed model. CONCLUSIONS: The study findings confirm a consistent and reliable model of the instrument, through a combination of techniques. Considering the importance of using solid instruments in clinical practice, CuidaSM is a promising tool for population-based management and network care organization, aligned with HCP proposals.

Trust matters: The Addressing Vaccine Hesitancy in Europe Study.

This article presents the design of a seven-country study focusing on childhood vaccines, Addressing Vaccine Hesitancy in Europe (VAX-TRUST), developed during the COVID-19 pandemic. The study consists of (a) situation analysis of vaccine hesitancy (examination of individual, socio-demographic and macro-level factors of vaccine hesitancy and analysis of media coverage on vaccines and vaccination and (b) participant observation and in-depth interviews of healthcare professionals and vaccine-hesitant parents. These analyses were used to design interventions aimed at increasing awareness on the complexity of vaccine hesitancy among healthcare professionals involved in discussing childhood vaccines with parents. We present the selection of countries and regions, the conceptual basis of the study, details of the data collection and the process of designing and evaluating the interventions, as well as the potential impact of the study. Laying out our research design serves as an example of how to translate complex public health issues into social scientific study and methods.

A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

Touching the cornerstone: An illustrative example of the effects of stigma and discrimination on vaccine-hesitant parents.

Objectives: The concept of vaccine hesitancy encompasses multiple views on the subject. However, there has been an increasing polarization of the discourse on vaccine hesitancy leading to the stigmatization of those parents who expressed doubts or concerns regarding vaccination practices. The present study aimed to explore the drivers and consequences of polarized discourses on vaccination in the Portuguese context. This paper is part of a broader study which aims to gain a deeper understanding about the phenomenon of vaccine hesitancy at the European level. Study design: A qualitative research design was used. Methods: The sample was comprised of thirty-one Portuguese vaccine hesitant parents who were interviewed. A thematic analysis of the transcribed interviews was performed which allowed us to identify key themes. Results: The results showed that the labelling of vaccine-hesitant parents as 'anti-vaxxers' along with social media play a crucial role in promoting the polarization of vaccine-related attitudes. The stigmatization of vaccine hesitant parents has a disruptive impact on their social network leading them to search for online platforms where they can exchange vaccines-related information without being discriminated. Conclusions: The stigma and discrimination experienced by vaccine-hesitant parents stimulated that hesitancy becomes more entrenched. Therefore, pluralism should be used to tailor vaccination promotion campaigns to different targets, promoting its reach and efficacy.

Recruiting a Hard-to-Reach, Hidden and Vulnerable Population: The Methodological and Practical Pitfalls of Researching Vaccine-Hesitant Parents.

While recruitment is an essential aspect of any research project, its challenges are rarely acknowledged. We intend to address this gap by discussing the challenges to the participation of vaccine-hesitant parents defined here as a hard-to-reach, hidden and vulnerable population drawing on extensive empirical qualitative evidence from seven European countries. The difficulties in reaching vaccine-hesitant parents were very much related to issues concerning trust, as there appears to be a growing distrust in experts, which is extended to the work developed by researchers and their funding bodies. These difficulties have been accentuated by the public debate around COVID-19 vaccination, as it seems to have increased parents' hesitancy to participate. Findings from recruiting 167 vaccine-hesitant parents in seven European countries suggest that reflexive and sensible recruitment approaches should be developed.

A New Era in Salivary Gland Carcinoma Treatment: A Case Report.

Salivary gland cancers are rare and heterogenous malignancies which makes it hard to standardize treatments with good evidence levels. The localized disease approach is well established, with surgery to the primary site and adjuvant radiation therapy in patients with high-risk features. Treatment of advanced disease should be multidisciplinary. Local approaches, which include radiation therapy, surgery, and thermoablation, among others, have the potential to achieve durable disease control with low toxicity. Chemotherapy has shown disappointing results, so systemic treatment should be guided by actionable genetic alterations, which in salivary gland cancers rely on the histologic type. When directed molecular tests are not useful, a multigene panel should be performed. This case is a good example of how to integrate all these possible tretaments in clinical practice, including molecular testing and target treatment.

Distribution and Clinical Significance of HPV16 Variants in Head and Neck Squamous Cell Carcinomas: Data from a Portuguese Cohort and Systematic Review.

INTRODUCTION: Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aimed to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical pathological characteristics and patient survival. METHODS: We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis. Targeted next-generation sequencing was used to obtain whole-genome sequences, and variants were established based on phylogenetic classification. RESULTS: 74% of samples clustered in lineage A, 5.7% in lineage B, 2.9% in lineage C, and 17.1% in lineage D. Comparative genome analysis revealed 243 single nucleotide variations. Of these, one hundred were previously reported, according to our systematic review. No significant associations with clinical pathological variables or patient survival were observed. The E6 amino acid variations E31G, L83V, and D25E and E7 N29S, associated with cervical cancer, were not observed, except for N29S in a single patient. CONCLUSION: These results provide a comprehensive genomic map of HPV16 in HSNCC, highlighting tissue-specific characteristics which will help design tailored therapies for cancer patients.

Prevalence Rate of Thalassemia Carriers among Individuals with Microcytosis or Hypochromia in Portugal.

INTRODUCTION: Microcytosis and hypochromia result from deficient hemoglobin synthesis in red blood cells and are easily detected in a complete blood count test. These conditions are mainly due to iron nutritional deficiency, but may also result from some genetic diseases, such as thalassemia. The aim of this study was to determine the contribution of ß- and α-thalassemia to these abnormal hematological phenotypes in a representative sample of adult individuals living in Portugal who participated in the first Portuguese National Health Examination Survey (INSEF). MATERIAL AND METHODS: Among the 4808 INSEF participants, 204 had microcytosis, hypochromia or both. The corresponding 204 DNAs were screened for changes in the ß-globin gene by next-generation sequencing and Sanger sequencing. In addition, α-thalassemia deletions within the α-globin cluster were investigated by Gap-PCR and multiplex ligation-dependent probe amplification. RESULTS: In this selected subgroup of INSEF participants, 54 had α-thalassemia (26%), predominantly caused by the -α3.7kb deletion, and 22 were ß-thalassemia carriers (11%) mainly due to point mutations in the ß-globin gene previously known in Portugal. CONCLUSION: Thalassemia trait is a frequent cause of microcytosis or hypochromia in Portugal since this genetic condition was found in 37% of the investigated cases.

Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in Portugal.

Chemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.

The knowledge of primary health care professionals regarding mental health: diagnosis by mhGAP / Conhecimento de profissionais da atenção primária em saúde mental: diagnóstico pelo mhGAP

ABSTRACT OBJECTIVE To analyze knowledge about priority topics in mental health care of strategic actors who work in regions where the Health Care Planning (PAS) methodology is used. METHODS This is a quantitative, descriptive, cross-sectional, and observational study carried out with professionals from six health regions, distributed in three Brazilian states (Goiás, Rondônia and Maranhão) and linked to the project "Saúde mental na APS" (Mental health in PHC) of the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (Proadi-SUS - Institutional Development Support Program of the Brazilian Unified Health System). The sample was made up of professionals who participated in the intervention guide multiplier training stage for mental, neurological and alcohol and other drug use disorders in the primary health care network, from July to September 2022. Data collection was through a self-administered instrument, in electronic format, consisting of a block with socioeconomic items and a structured questionnaire to assess participants' knowledge about priority topics in mental health. Descriptive analyses and comparison of proportions were conducted to analyze the data. RESULTS A total of 354 health professionals participated in the study. Regarding the percentage of correct answers in the questionnaire on priority topics in mental health, the highest medians were identified in the "Depression" module. On the other hand, the content referring to the modules "Essential care and practices" and "Other important complaints" presented the lowest values. Furthermore, some participant characteristics were found to be associated with the percentage of correct answers in the questionnaire modules. CONCLUSIONS The findings reveal opportunities for improvement, mainly in knowledge related to communication skills and the approach to emotional and physical distress without diagnostic criteria for a specific disease, offering support for planning actions aimed at intensifying the consideration of these themes during the operational stages of PAS.

RESUMO OBJETIVO Analisar o conhecimento sobre temas prioritários do cuidado em saúde mental de atores estratégicos que atuam em regiões nas quais se utiliza a metodologia da Planificação da Atenção à Saúde (PAS). MÉTODOS Trata-se de um estudo quantitativo, descritivo, transversal e observacional realizado com profissionais de seis regiões de saúde, distribuídas em três estados brasileiros (Goiás, Rondônia e Maranhão) e vinculadas ao projeto "Saúde mental na APS" do Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (Proadi-SUS). A amostra foi composta por profissionais que participaram da etapa de formação de multiplicadores do manual de intervenções para transtornos mentais, neurológicos e por uso de álcool e outras drogas na rede de atenção básica à saúde, no período de julho a setembro de 2022. A coleta de dados foi realizada a partir de um instrumento autoaplicável, em formato eletrônico, composto por um bloco com itens socioeconômicos e um questionário estruturado para avaliação do conhecimento dos participantes acerca de temas prioritários em saúde mental. Para análise dos dados, foram empreendidas análises descritivas e comparação de proporções. RESULTADOS Participaram do estudo 354 profissionais de saúde. Em relação ao percentual de acerto no questionário sobre temas prioritários em saúde mental, as medianas mais altas foram identificadas no módulo de "Depressão". Em contrapartida, o conteúdo referente aos módulos "Cuidados e práticas essenciais" e "Outras queixas importantes" apresentaram os valores mais baixos. Além disso, identificou-se que algumas características dos participantes apresentaram associações com o percentual de acertos nos módulos do questionário. CONCLUSÕES Os achados revelam oportunidades de melhoria, principalmente no conhecimento relacionado às habilidades de comunicação e a abordagem ao sofrimento emocional e físico sem critérios diagnósticos para uma doença específica, oferecendo subsídios para o planejamento de ações que visem a intensificação do olhar destas temáticas durante as etapas operacionais da PAS.

Brazilian Scale for Evaluation of Mental Health Care Needs: Additional Evidence / Escala de Avaliação da Necessidade de Cuidado em Saúde Mental: evidências adicionais

ABSTRACT OBJECTIVE To investigate validity evidence of the Brazilian Scale for Evaluation of Mental Health Care Needs (CuidaSM). METHODS This is a psychometric study, which seeks additional evidence of internal structure. Data collection was carried out in 11 Primary Health Care (PHC) services , which implement the Health Care Planning (HCP) methodology, distributed across the five Brazilian regions. The preliminary version of CuidaSM, containing a block self-referred by the user and another block evaluated by PHC professionals, was applied to users aged 18 or over who attended the PHC services for consultation with a higher education professional. The techniques of confirmatory factor analysis and network analysis were used to investigate validity evidence. For the primary data of the confirmatory factor analysis, the factorial loads and the item's predictive power (R2) were used. Six model adjustment indices were adopted and reliability was measured by three indicators using Bayesian estimation. RESULTS A total of 879 users participated in the study. By confirmatory factor analysis, factorial loads ranged from 0.43 to 0.99 and R2 from 0.19 to 0.98. Both the primary indicators and the model adequacy indices were established at satisfactory and consistent levels. The network analysis showed that the items were appropriately associated with their peers, respecting the established dimensions, which again indicates the sustainability and stability of the proposed model. CONCLUSIONS The study findings confirm a consistent and reliable model of the instrument, through a combination of techniques. Considering the importance of using solid instruments in clinical practice, CuidaSM is a promising tool for population-based management and network care organization, aligned with HCP proposals.

RESUMO OBJETIVO Investigar evidências de validade da Escala de Avaliação da Necessidade de Cuidado em Saúde Mental (CuidaSM). MÉTODOS Trata-se de um estudo de natureza psicométrica, que busca evidências adicionais de estrutura interna. A coleta de dados foi realizada em 11 unidades básicas de saúde (UBS), que executam a metodologia da Planificação da Atenção à Saúde (PAS), distribuídas nas cinco regiões brasileiras. A versão preliminar da CuidaSM, contendo um bloco autorreferido pelo usuário e outro avaliado por profissionais da atenção primária à saúde (APS), foi aplicada em usuários com 18 anos ou mais que compareceram às UBS para consulta com profissional de nível superior. As técnicas de análise fatorial confirmatória e network analysis foram utilizadas para investigação das evidências de validade. Para os dados primários da análise fatorial confirmatória, utilizou-se as cargas fatoriais e o poder preditivo do item (R2). Foram adotados seis índices de ajustamento do modelo e a confiabilidade foi aferida por três indicadores por meio de bayesian estimation. RESULTADOS Participaram do estudo 879 usuários. Pela análise fatorial confirmatória, as cargas fatoriais variaram de 0,43 a 0,99 e R2 de 0,19 a 0,98. Tanto os indicadores primários como os índices de adequação do modelo estabeleceram-se em níveis satisfatórios e consistentes. A network analysis apontou que os itens se associaram de forma adequada a seus pares, respeitando as dimensões estabelecidas, o que indica, novamente, a sustentabilidade e estabilidade do modelo proposto. CONCLUSÕES Os achados do estudo confirmam um modelo consistente e confiável do instrumento, por meio da combinação de técnicas. Considerando a relevância do uso de instrumentos sólidos na prática clínica, a CuidaSM se apresenta como uma ferramenta promissora para a gestão de base populacional e organização do cuidado em rede, alinhada às propostas da PAS.

Characterization of the Human Papillomavirus 16 Oncogenes in K14HPV16 Mice: Sublineage A1 Drives Multi-Organ Carcinogenesis.

The study of human papillomavirus (HPV)-induced carcinogenesis uses multiple in vivo mouse models, one of which relies on the cytokeratin 14 gene promoter to drive the expression of all HPV early oncogenes. This study aimed to determine the HPV16 variant and sublineage present in the K14HPV16 mouse model. This information can be considered of great importance to further enhance this K14HPV16 model as an essential research tool and optimize its use for basic and translational studies. Our study evaluated HPV DNA from 17 samples isolated from 4 animals, both wild-type (n = 2) and HPV16-transgenic mice (n = 2). Total DNA was extracted from tissues and the detection of HPV16 was performed using a qPCR multiplex. HPV16-positive samples were subsequently whole-genome sequenced by next-generation sequencing techniques. The phylogenetic positioning clearly shows K14HPV16 samples clustering together in the sub-lineage A1 (NC001526.4). A comparative genome analysis of K14HPV16 samples revealed three mutations to the human papillomaviruses type 16 sublineage A1 representative strain. Knowledge of the HPV 16 variant is fundamental, and these findings will allow the rational use of this animal model to explore the role of the A1 sublineage in HPV-driven cancer.

Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer.

BACKGROUND: Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors. AIM: To assess blood ratios' (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients. METHODS: This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable. RESULTS: This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time (r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT (P = 0.022) and mortality (P = 0.013), with high PLR patients having a 2.2-times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5-times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR, and high LMR patients had a 1.4-times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR (P = 0.015) and partial/complete TRG (P < 0.001). Patients without TSR and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death. CONCLUSION: Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying.

Parallel Propagation of Toxoplasma gondii In Vivo, In Vitro and in Alternate Model: Towards Less Dependence on the Mice Model.

Toxoplasma gondii is an obligate intracellular protozoan. In pregnant women, it can lead to severe birth defects or intrauterine death of the fetus. Most of what is currently know on cell biology of T. gondii comes from studies relying on the RH strain propagated in mice. According to the recommendations concerning the animal welfare, we assayed in vitro/in vivo procedures to replace, or at least reduce, the demanding animal model for strain propagation. We evaluated the genetic and phenotypic stability of the RH strain throughout its parallel continuous propagation in mice, in human foreskin fibroblasts (HFF) and in an alternate fashion of these two procedures. We also assessed the virulence impact on the RH strain after different periods of its long-term propagation strictly in cells. The RH strain completely lost its virulence after long-term passage in HFF. Nevertheless, we obtained a successful outcome with the alternate passaging of the parasite in HFF and in mice as this approach enabled T. gondii to maintain the evaluated phenotypic properties, mainly its virulence potential. Also, no genetic changes were observed in genes known to be highly polymorphic or involved in pathoadaptation. In conclusion, the alternate model seems to be a feasible method for T. gondii propagation and maintenance, strongly impacting the number of sacrificed mice.

Clostridium difficile Severity and Outcome at a North of Portugal Healthcare Facility.

INTRODUCTION: Clostridium difficile infection has been increasingly reported, with a significant healthcare burden and important morbimortality. This study aimed to characterize and describe the severity and outcomes of this event at a Portuguese hospital. MATERIAL AND METHODS: We conducted a retrospective analysis, by clinical record review, of all confirmed cases diagnosed in a hospital in the North of Portugal, between January 2013 and December 2018. We included those who were non-pregnant and at least 18 years old. RESULTS: Fifty-seven cases occurred, mostly in females and aged patients; 33.3% were healthcare facility-outset, while 31.6% were community-associated. Regarding severity, 43.9% had non-severe, while 29.8% severe and 21.0% fulminant presentations, the latter with the need of admission. Exposure to antibiotics occurred in 68.4%, while to proton-pump inhibitors in 57.9%. Risk factors for severe disease were female gender, chronic renal disease, and high neutrophil-lymphocyte ratio. Moreover, renal disease and a higher ratio were associated with fulminant disease. Thirty-day all-cause mortality was found in 15.8% while 90-day in 28.1%. Risk factors for 30-day mortality were renal disease, higher Charlson score, and higher neutrophil-lymphocyte ratio. Risk factors for 90-day mortality were advanced age, previous antibiotic exposure, higher Charlson score, and higher neutrophil-lymphocyte ratio. CONCLUSION: Data concerning Clostridium difficile infection severity and prognosis in Portugal is scarce, and future studies should focus on this important topic.

Introdução: A infeção por Clostridium difficile tem aumentado, com importante morbimortalidade e impacto nos sistemas de saúde. Este estudo procurou caracterizar e descrever a severidade e prognóstico desta infeção, na nossa instituição. Material e Métodos: Realizou-se uma análise retrospetiva dos casos confirmados ocorridos entre janeiro de 2013 e dezembro de 2018, num hospital do Norte de Portugal. Recorreu-se à análise de processo clínico e foram incluídos doentes sem gravidez em curso e com pelo menos 18 anos. Resultados: Verificaram-se 57 casos, a maioria em mulheres e idosos, sendo que 33,3% tiveram origem em instituições de saúde e 31,6% na comunidade. Nesta amostra, 43,9% tiveram doença não severa, 29,8% severa e 21,0% fulminante, estes com necessidade de internamento. A toma prévia de antibióticos ocorreu em 68,4%, e de inibidores da bomba de protões em 57,9%. O sexo feminino relacionou-se com doença severa, enquanto que a doença renal crónica e um elevado rácio neutrófilos-linfócitos se relacionaram com doença severa e fulminante. A mortalidade aos 30 dias verificou-se em 15,8% e associou-se a doença renal e elevação do score de Charlson e do rácio neutrófilos-linfócitos. A mortalidade aos 90 dias ocorreu em 28,1%, associada a idade avançada, toma de antibióticos e elevação do score e do rácio. Conclusão: Em Portugal, são escassos os dados sobre a severidade e prognóstico desta infeção, pelo que são necessários mais estudos nacionais.

ATENA-A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation.

Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator. Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use. Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models. Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo. Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia.

We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb-thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width. Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.