Predictors of in-hospital mortality in elderly patients with bacteraemia admitted to an Internal Medicine ward

BACKGROUND: Infectious diseases are a common cause of increased morbidity and mortality in elderly patients. Bacteraemia in the elderly is a difficult diagnosis and a therapeutic challenge due to age-related vicissitudes and to their comorbidities. The main purpose of the study was to assess independent risk factors for in-hospital mortality among the elderly with bacteraemia admitted to an Internal Medicine Ward. METHODS: Overall, a cohort of 135 patients, 65 years of age and older, with bacteraemia were retrospectively studied. Data related to demographic information, comorbidities, clinical parameters on admission, source and type of infection, microorganism isolated in the blood culture, laboratory data and empirical antibiotic treatment was recorded from each patient. Multivariate logistic regression was performed to identify independent predictors of all-cause in-hospital mortality. RESULTS: Of these 135 patients, 45.9% were women. The most common infections in this group of patients were urinary tract infections (46.7%). The main microorganisms isolated in the blood cultures were Escherichia coli (14.9%), Methicillin-resistant Staphylococcus aureus (MRSA) (12.0%), non-MRSA (11.4%), Klebsiella pneumoniae (9.1%) and Enterococcus faecalis (8.0%). The in-hospital mortality was 22.2%. Independent prognostic factors associated with in-hospital mortality were age ≥ 85 years, chronic renal disease, bacteraemia of unknown focus and cognitive impairment at admission (OR, 2.812 [95% CI, 1.039-7.611; p = 0.042]; OR, 6.179 [95% CI, 1.840-20.748; p = 0.003]; OR, 8.673 [95% CI, 1.557-48.311; p = 0.014] and OR, 3.621 [95% CI, 1.226-10.695; p = 0.020], respectively). By multivariate analysis appropriate antibiotic therapy was not associated with lower odds of mortality. CONCLUSION: Bacteraemia in the elderly has a high mortality rate. There are no set of signs or clinical features that can predict bacteraemia in the elderly. However, older age (≥ 85 years), chronic renal disease, bacteraemia of unknown focus and severe cognitive impairment adversely affects the outcome of elderly patients with bacteraemia admitted to an Internal Medicine ward

Clinical and molecular characterisation of metastatic papillary thyroid cancer according to radioiodine therapy outcomes

Funding Information: This study was funded by iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344; UID/Multi/00462; UIDB/04462/2020), a program co-funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência e do Ensino Superior, Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo (SPEDM), and Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). J.S.-P. was supported by iNOVA4Health – UIDB/04462/2020. M.P. was granted by Liga Portuguesa Contra o Cancro, Núcleo Regional do Sul (LPCC-NRS). R.R. was granted with a PhD scholarship by iNOVA4Health Research Unit - UIDP/04462/2020; UI/BD/154256/2022. C.P. was granted with a PhD scholarship by FCT – 2020.07120.BD. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Purpose: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. Methods: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. Results: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients’ primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). Conclusions: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.publishersversionepub_ahead_of_prin

SPRY4 as a Potential Mediator of the Anti-Tumoral Role of Macrophages in Anaplastic Thyroid Cancer Cells

Funding Information: This work was funded by MERCK in collaboration with Grupo de Estudos da Tiroide (GET) from Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo (SPEDM) (MERCK/GET/SPEDM/2017), by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associated Laboratory LS4FUTURE (LA/P/0087/2020), by Associação de Endocrinologia Oncológica (AEO/2017), and by Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG/2017). Marta Pojo was granted by Liga Portuguesa Contra o Cancro—Núcleo Regional do Sul (LPCC-NRS/2017). Carolina Pires was granted with a Ph.D. scholarship by FCT—2020.07120.BD. Ricardo Rodrigues was granted with a Ph.D. scholarship by iNOVA4Health Research Unit—UIDP/04462/2020; UI/BD/154256/2022. Publisher Copyright: © 2023 by the authors.Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p < 0.01; p < 0.01), contrasting with a decrease in C3948 (p < 0.001; p < 0.05), with mild effects in T238 migration (p < 0.01) and C643 invasion (p < 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p < 0.05) and C3948 (p < 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α; p < 0.05) in C3948–macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture. SPRY4 silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness. SPRY4 is a possible modulator of macrophage–ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes.publishersversionpublishe

The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner.

A variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored the function of BOK in a mutant KrasG12D-driven murine model of lung cancer. Using KrasG12D/+ Bok-/- mice, we observed an overall tumor-promoting function of BOK in vivo. Specifically, loss of BOK reduced proliferation both in cell lines in vitro as well as in KrasG12D-driven tumor lesions in vivo. During tumor development in vivo, loss of BOK resulted in a lower tumor burden, with fewer, smaller, and less advanced tumors. Using KrasG12D/+ Tp53Δ/Δ Bok-/- mice, we identified that this phenotype was entirely dependent on the presence of functional p53. Furthermore, analysis of a human dataset of untreated early-stage lung tumors did not identify any common deletion of the BOK locus, independently of the TP53 status or the histopathological classification. Taken together our data indicate that BOK supports tumor progression in Kras-driven lung cancer

Diagnóstico del funcionamiento del Programa de Administración de la Caja de Seguro Social y alternativas para mejorar su eficiencia

Objetivo general: Elaborar una propuesta que contribuya a mejorar la eficiencia administrativa, funcional, económica y financiera del Programa de Administración de la Caja de Seguro Social. Objetivos específicos 1. Identificar los procesos que hacen ineficiente el Programa de Administración de la Caja de Seguro Social. 2. Analizar indicadores económicos y bases biométricas 3. Proponer cambios estructurales, funcionales y modificaciones a la Ley Orgánica que permitan el equilibrio financiero y la eficiencia administrativa de la Institución

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL’HIV open-label, factorial randomised controlled trial

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL’HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$–421 per year [95$ –2620.4 [95% CI –2864.3 to –2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. Trial registration: ClinicalTrials.gov NCT03160105

Diagnóstico del funcionamiento del Programa de Administración de la Caja de Seguro Social y alternativas para mejorar su eficiencia

Objetivo General: Elaborar una propuesta que contribuya a mejorar la eficiencia administrativa, funcional, económica y financiera del Programa de Administración de la Caja de Seguro Social. Objetivos Específicos 1. Identificar los procesos que hacen ineficiente el Programa de Administración de la Caja de Seguro Social. 2. Analizar indicadores económicos y bases biométricas 3. Proponer cambios estructurales, funcionales y modificaciones a la Ley Orgánica que permitan el equilibrio financiero y la eficiencia administrativa de la Institución

Role of the HIV-1 Reservoir to Maintain Viral Suppression in a Simplified Strategy for the Long-Term Management of HIV-1 Infection (The SIMPL’HIV Trial).

HIV-1 reservoir size and dynamics are promising parameters to ensure the safe prescription of simplified maintenance antiretroviral therapy in chronically HIV-1 infected patients. In the SIMPL’HIV trial, HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained at baseline and week 48 to investigate changes over time and evidence of a predictive relationship to maintain HIV-1 RNA <20 copies/ml. Measurements were available for 175 patients, with no differences observed between treatment strategies. Findings showed that baseline HIV-1 DNA was lower in those with durable HIV-1 RNA <20 copies/ml compared with patients with incomplete viral suppression over 48 weeks

Review of multiple hazards in volcanic islands to enable the management of long-term risks: the cases of Ischia and Vulcano, Italy

The management of long-term volcanic risks represents a challenge that requires a close cooperation between science and decision-making. This is particularly crucial in volcanic islands, which are characterized by multiple hazards concentrated in a relatively small environment, often associated with a large seasonality of exposure due to tourism. The scientific challenges are mainly the quantification and the characterization of the interactions among the multiple hazardous phenomena that may occur during the different “states of thevolcano” (quiescence, unrest, eruption) and the definition of robust methods to forecast the transition between these states. For these topics, the emerging scientific knowledge is often rather limited and uncertain and, also in case it was well constrained, difficult to communicate to decision makers due to its intrinsic complexity. On the other side, the challenge for decision making is to assimilate this uncertain knowledgeand translate it into actions. Here, we discuss the experience gained in two working groups (WGs) in charge of reviewing the state of knowledge about volcanic hazards for the Italian volcanic islands of Ischia and Vulcano to build the scientific ground for subsequent decision making. These WGs, formed within the agreement between INGV and the Italian Civil Protection Department, involved about 20 researchers from INGV and Universities, as well as representatives of the Italian Civil Protection, to facilitate the reciprocal understanding and to address the work toward useful results for decision making. The WGs reviewed all the potential volcanic hazards for Ischia and Vulcano based on literature, results of previous projects, as well as ad hoc audits of other experts on specific topics, and organized a workshop to present the results and receive feedbacks from the extended scientific community