RESUMO
EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Humanos , Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/patologia , Linfócitos T Citotóxicos/metabolismo , Tolerância Imunológica , Microambiente TumoralRESUMO
BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
Assuntos
Diabetes Mellitus Tipo 2 , Glomerulonefrite , Nefropatias , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Nefropatias/complicações , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/complicações , Proteinúria/etiologia , Proteinúria/complicações , Albumina Sérica , Sódio , Glucose , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.
Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/efeitos adversos , Infliximab/efeitos adversos , Psoríase/tratamento farmacológico , Psoríase/patologia , Fatores Imunológicos/uso terapêutico , Necrose/induzido quimicamenteRESUMO
BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.
Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/efeitos adversos , Infliximab/efeitos adversos , Psoríase/tratamento farmacológico , Psoríase/patologia , Fatores Imunológicos/uso terapêutico , Necrose/induzido quimicamenteRESUMO
OBJECTIVE: To assess the efficiency of Dyevert™ Power XT compared to the standard clinical practice when used for percutaneous coronary interventions (PCI). METHODS: A Markov model was developed to estimate, over 3-month cycles and a lifetime time horizon, the cumulative costs and health outcomes (life years gained [LYG] and quality-adjusted life years [QALY]) in a hypothetical cohort of 1,000 patients with chronic kidney disease (CKD) 3b-4 and an average age of 72 years. The incidence of contrast-induced acute kidney injury for these patients is 18.89% in routine practice and 7.78% with Dyevert. QALYs were estimated by applying utilities by health state. Transitions between states and utilities were obtained from the literature. Overall all-cause and state-specific mortality were considered. The total cost (2,022) estimated with the National Health System perspective included cost of the procedure and of CKD management. The parameters were validated by a panel of experts. A discount rate (3% per year) was applied to costs and outcomes. RESULTS: The use of Dyevert yielded more health benefits (34.60 LYG and 5.69 QALYs) compared to the current standard practice (33.11 LYG and 5.38 QALYs). Lifetime cost accumulated at the end of the simulation resulted 30,211/patient with Dyevert and 33,895/patient with current standard clinical practice. CONCLUSIONS: The use of Dyevert™ Power XT resulted dominant option, due to its higher effectiveness and lower cost as compared to standard clinical practice and, therefore, a preferred option in patients with CKD stages 3b-4 undergoing PCI in Spain.
Assuntos
Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Humanos , Idoso , Análise de Custo-Efetividade , Espanha/epidemiologia , Análise Custo-Benefício , Resultado do Tratamento , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
PURPOSE: Onflex™ mesh has replaced Polysoft™ patch on the market, without being clinically evaluated thus far in the transinguinal preperitoneal (TIPP) technique. METHODS: All consecutive TIPP registered in our registry during the overlap period of availability of both meshes were included and studied with the chronic postoperative inguinal pain (CPIP) as primary endpoint, assessed with a verbal rating scale (VRS), and included in a patient-related outcome measurement (PROM) phone questionnaire. RESULTS: A total of 181 Onflex cases vs 182 Polysoft cases were studied with a 2-year follow-up rate of 92% vs 88%. The overall rate of pain or discomfort was not statistically different in the 2 studied subgroups (16.5% vs 17.6%; p = 0.71), while moderate or severe pain were significantly more frequent in the Polysoft subgroup (5.5% vs 11.6%; p = 0.01). These symptoms did not interfere with the patient daily life in 16% vs 16.5% of cases, and they were self-assessed as more bothersome than the hernia in only 0.5% vs 0.5% of cases, suggesting an overestimation of the pain by the VRS. Patients assessed the result of their hernia repair as excellent or good in 97.8% vs 96.7% and medium or bad in 2.2% vs 3.3% (p = 0.53). The cumulative recurrence rate was 0% vs 2.2%. Two reoperations (one for early and one for late recurrence) were reported in the Polysoft subgroup (1%), none related to the non-absorbable memory ring. CONCLUSIONS: These results suggest that TIPP with Onflex provides results at least similar than those with Polysoft.
Assuntos
Dor Crônica , Hérnia Inguinal , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Seguimentos , Virilha/cirurgia , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Humanos , Dor Pós-Operatória/epidemiologia , Recidiva , Sistema de Registros , Telas Cirúrgicas/efeitos adversosRESUMO
The advent of stem cell-derived retinal organoids has brought forth unprecedented opportunities for developmental and physiological studies, while presenting new therapeutic promise for retinal degenerative diseases. From a translational perspective, organoid systems provide exciting new prospects for drug discovery, offering the possibility to perform compound screening in a three-dimensional (3D) human tissue context that resembles the native histoarchitecture and to some extent recapitulates cellular interactions. However, inherent variability issues and a general lack of robust quantitative technologies for analyzing organoids on a large scale pose severe limitations for their use in translational applications. To address this need, we have developed a screening platform that enables accurate quantification of fluorescent reporters in complex human iPSC-derived retinal organoids. This platform incorporates a fluorescence microplate reader that allows xyz-dimensional detection and fine-tuned wavelength selection. We have established optimal parameters for fluorescent reporter signal detection, devised methods to compensate for organoid size variability, evaluated performance and sensitivity parameters, and validated this technology for functional applications.
Assuntos
Técnicas Genéticas , Células-Tronco Pluripotentes Induzidas/citologia , Organoides/fisiologia , Retina/fisiologia , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Corantes Fluorescentes , Genes Reporter , Humanos , Microscopia de Fluorescência , Estresse Oxidativo , Transplante de Células-Tronco , Transgenes , Pesquisa Translacional BiomédicaRESUMO
The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naïve pluripotent states has a wide impact in human developmental biology. However, hPSCs are unstable in classical naïve mouse embryonic stem cell (ESC) WNT and MEK/ERK signal inhibition (2i) culture. We show that a broad repertoire of conventional hESC and transgene-independent human induced pluripotent stem cell (hiPSC) lines could be reverted to stable human preimplantation inner cell mass (ICM)-like naïve states with only WNT, MEK/ERK, and tankyrase inhibition (LIF-3i). LIF-3i-reverted hPSCs retained normal karyotypes and genomic imprints, and attained defining mouse ESC-like functional features, including high clonal self-renewal, independence from MEK/ERK signaling, dependence on JAK/STAT3 and BMP4 signaling, and naïve-specific transcriptional and epigenetic configurations. Tankyrase inhibition promoted a stable acquisition of a human preimplantation ICM-like ground state via modulation of WNT signaling, and was most efficacious in efficiently reprogrammed conventional hiPSCs. Importantly, naïve reversion of a broad repertoire of conventional hiPSCs reduced lineage-primed gene expression and significantly improved their multilineage differentiation capacities. Stable naïve hPSCs with reduced genetic variability and improved functional pluripotency will have great utility in regenerative medicine and human disease modeling.
Assuntos
Diferenciação Celular/fisiologia , Autorrenovação Celular/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Tanquirases/antagonistas & inibidores , Via de Sinalização Wnt/fisiologia , Animais , Proteína Morfogenética Óssea 4/metabolismo , Células Cultivadas , Reprogramação Celular/fisiologia , Camadas Germinativas/embriologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Humanos , Janus Quinases/metabolismo , Fator Inibidor de Leucemia/metabolismo , Camundongos , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Psoriasis is a very prevalent systemic chronic inflammatory disease. Major cardiovascular events are the main cause of mortality in these patients which suggests an association between psoriasis and traditional cardiovascular risk factors. OBJECTIVE: To identify classic cardiovascular risk factors and metabolic syndrome (MS) in patients with psoriasis, their possible association with its severity and compare it with the non-psoriatic population. METHODS: This is an observational and cross-sectional population study in Lleida (Spain) from a joint hospital/primary care database. RESULTS: The database comprised 398 701 individuals. There were 6868 cases registered as psoriasis (1.7%), and 499 of them (7.3%) were classified as moderate-severe psoriasis. Patients with psoriasis had a higher prevalence of traditional cardiovascular risk factors than non-psoriatic population: diabetes mellitus 2 (13.9% vs 7.4%, OR 2.01), dyslipidaemia (28.8% vs 17.4%, OR 1.92), arterial hypertension (31.2% vs 19.0%, OR 1.93), obesity (33.7% vs 28.1%, OR 1.30), altered fasting basal glycaemia (21.4% vs 15.1%, OR 1.54), low cholesterol HDL (38.1% vs 32.3%, OR 1.29), hypertriglyceridaemia (45.7% vs 35.2%, OR 1.55) and high waist circumference (75.7% vs 72.3%, OR 1.19). MS was more prevalent in psoriatic patients (28.3% vs 15.1%, OR 2.21), and cardiovascular risk factors were similar between psoriasis severity groups. Psoriatic patients had a higher prevalence of ischaemic heart disease (3.3% vs 1.8%, OR 1.87) and vascular cerebral accidents (1.8% vs 1.2%, OR 1.55). A model for MS showed a significant nonlinear relationship with age and sex and significant differences between patients with and without psoriasis. CONCLUSION: We found statistically significant differences in relation to the prevalence of cardiovascular risk factors, MS and major cardiovascular events in psoriatic patients. However, differences were not seen between psoriasis severity groups. Our work reinforces the need for a multidisciplinary approach and close monitoring of cardiovascular risk factors in these patients to prevent a cardiovascular event.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Psoríase/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Hipertrigliceridemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Prevalência , Psoríase/sangue , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Circunferência da Cintura , Adulto JovemRESUMO
BACKGROUND: Children with multimorbid asthma and rhinitis show IgE polysensitization to several allergen sources. This association remains poorly studied in adolescents and adults using defined allergen molecules. We investigated IgE sensitization patterns towards a broad panel of aeroallergen components in adults and adolescents with a focus on individuals with asthma and rhinitis multimorbidity. METHODS: IgE reactivity to 64 micro-arrayed aeroallergen molecules was determined with the MeDALL-chip in samples from the French EGEA study (n = 840, age = 40.7 ± 17.1) and the Swedish population-based birth cohort BAMSE (n = 786, age = 16 ± 0.26). The age- and sex-adjusted associations between the number of IgE-reactive allergen molecules (≥0.3 ISU) and the asthma-rhinitis phenotypes were assessed using a negative binomial model. RESULTS: Groups representing 4 phenotypes were identified: no asthma-no rhinitis (A-R-; 30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A-R+; 15% and 24%) and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE-reactive aeroallergen molecules significantly differed between phenotypes (median in A-R-, A+R-, A-R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3 and 5 in BAMSE). As compared to A-R- subjects, the adjusted ratio of the mean number of IgE-reactive molecules was higher in A+R+ than in A+R- or A-R+ (10.0, 5.4 and 5.0 in EGEA and 7.2, 0.7 and 4.8 in BAMSE). CONCLUSION: The A+R+ phenotype combined the sensitization pattern of both the A-R+ and A+R- phenotypes. This multimorbid polysensitized phenotype seems to be generalizable to various ages and allergenic environments and may be associated with specific mechanisms.
Assuntos
Asma/epidemiologia , Asma/imunologia , Imunoglobulina E/imunologia , Rinite/epidemiologia , Rinite/imunologia , Adolescente , Adulto , Alérgenos , Comorbidade , Reações Cruzadas/imunologia , Feminino , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Vigilância em Saúde Pública , Suécia/epidemiologia , Adulto JovemRESUMO
In a cross-sectional study carried out in El Salvador between February 2016 and July 2017, self-sampling and human papillomavirus (HPV) testing was found to be highly acceptable among 2019 women who had not attended a cervical cancer screening in at least 3â¯years. Within this population, HPV positivity rates differed according to age, marital status, number of children, and lifetime sexual partners. The proportion of women who tested HPV positive or who were diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) was similar to the general population of the area. Among the reasons for failing to participate in previous screening programs, non-attending women described logistic concerns, but also erroneous beliefs regarding HPV and cervical cancer, misconceptions regarding the screening procedure, discomfort with male providers, and confidentiality fears. The aim of this study was to identify opportunities and challenges that emerged from the use of self-sampling and HPV testing as part of a public cervical cancer control effort in a low-resource setting.
Assuntos
Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Manejo de Espécimes/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Estudos Transversais , Detecção Precoce de Câncer/métodos , El Salvador , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , População Rural , Esfregaço Vaginal/métodosRESUMO
Few studies to date have examined the effect of the high temperatures attained during wildfire events on the pigments present in forest foliage. Here, we seek to analyse the main photosynthetic pigments in the leaves of the oak, cork oak and eucalyptus following a wildfire. We also subject leaves of these last two species to a range of contact temperatures (100-500 °C) in the laboratory using a muffle furnace. The samples were left in the muffle for two hours at 100, 150, 200, 250, 300, 350, 400 and 500 °C, in line with other soil study models (Úbeda et al., 2009; Düdaite et al., 2013). At temperatures above 250 °C, chromatography fails to detect any pigments. A minimal increase in temperature degrades chlorophyll, the process being more rapid in eucalyptus than in cork oak, while it increases pheophytin concentrations.
Assuntos
Eucalyptus , Incêndios , Fotossíntese , Quercus , FlorestasRESUMO
BACKGROUND: Accurate preoperative lymphoscintigraphy is vital to performing sentinel lymph node biopsy (SLNB) for cutaneous malignancies. Potential advantages of single-photon emission computed tomography with integrated computed tomography (SPECT/CT) include the ability to readily identify aberrant drainage patterns as well as provide the surgeon with three-dimensional anatomic landmarks not seen on conventional planar lymphoscintigraphy (PLS). METHODS: Patients with cutaneous malignancies who underwent SLNB with preoperative imaging using both SPECT/CT and PLS from 2011 to 2014 were identified. RESULTS: Both SPECT/CT and PLS were obtained in 351 patients (median age, 69 years; range, 5-94 years) with cutaneous malignancies (melanoma = 300, Merkel cell carcinoma = 33, squamous cell carcinoma = 8, other = 10) after intradermal injection of 99mtechnetium sulfur colloid (median dose 300 µCi). A mean of 4.3 hot spots were identified on SPECT/CT compared to 3.0 on PLS (p < 0.001). One hundred fifty-three patients (43.6 %) had identical findings between SPECT/CT and PLS, while 172 (49 %) had additional hot spots identified on SPECT/CT compared to only 24 (6.8 %) additional on PLS. SPECT/CT demonstrated additional nodal basins in 103 patients (29.4 %), compared to only 11 patients (3.1 %) with additional basins on PLS. CONCLUSIONS: SPECT/CT is a useful adjunct that can help with sentinel node localization in challenging cases. It identified additional hot spots not seen on PLS in almost 50 % of patients. Because PLS identified hot spots not seen on SPECT/CT in 6.8 % of patients, we recommend using both modalities jointly. Long-term follow-up will be required to validate the clinical significance of the additional hot spots identified by SPECT/CT.
Assuntos
Linfocintigrafia/métodos , Linfonodo Sentinela/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/diagnóstico por imagem , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Masculino , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Sarcoma/cirurgia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adulto JovemRESUMO
Introduction: The complex chronic disease requires a model of care based found on multidisciplinary teams. The aim of this study was to analyse the development of nursing leadership in managing the complex chronic patient (CCP) and to identify how the resources for the attention and follow up of these patients are managed. Method: A qualitative descriptive approach was followed through participant observation, in-depth interview to 7 health professionals (5 nurses, a doctor, and a social worker) and a discussion group with 9 Primary Health Care nurses from a intentional sample. Discourse analysis was undertaken following Conde approach: fixing discurse positions, creating and analyzing symbolic configuratons, analyzing and interpreting semantic configurations and drawing up the discourse. Results: From discourse analysis two main dimensions emerged on the nursing leadership and management: a) nursing as the leader of care: the need of nursing leadership and of improvement in the coordination structures were recognized, and b) nursing as resources manager in the CCP care related to social and health risks and resources coordination. Conclusions: Our findings enhance the case management and the home delivery care as foundations to be effective handle of CCP, where nursing has a privileged role.
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Doença Crônica/enfermagem , Continuidade da Assistência ao Paciente , Humanos , Liderança , Papel do Profissional de EnfermagemRESUMO
Peptide conjugates incorporating the N-based ligands (Me2)PyTACN or (S,S')-BPBP at the N- or the C-terminus of the cell-penetrating peptide were synthesized (PyTACN-BP16 (), BP16-PyTACN (), BPBP-BP16 (), and BP16-BPBP ()). Metal binding peptides bearing at the N-terminus the ligand, an additional Lys and a ß-Ala were also prepared (PyTACN-ßAK-BP16 () and BPBP-ßAK-BP16 ()). Moreover, taking into account the clathrin-dependent endocytic mechanism of , the enzymatic cleavable tetrapeptide Gly-Phe-Leu-Gly was incorporated between the ligand and the N- or C-terminus of (BPBP-GFLG-BP16 () and BP16-GLFG-BPBP ()). Analysis of the cytotoxicity of all the peptide conjugates showed that: (i) the position of the ligand influenced the IC50 values, (ii) the incorporation of the ßAla-Lys dipeptide rendered non active sequences, (iii) peptide conjugates derived from the (S,S')-BPBP ligand were more active than those bearing (Me2)PyTACN, and (iv) the introduction of the cleavable tetrapeptide significantly enhanced the activity of the BPBP conjugates (IC50 of 4.3 to 11.7 µM ( and ) compared to 26.0 to >50 µM (, and )). The most active peptide was BPBP-GFLG-BP16 () (IC50 of 4.3 to 5.0 µM). This high activity was attributed to its high internalization in MCF-7 cells, as shown by flow cytometry, and to the subsequent release of the ligand by the intracellular cleavage of the enzyme-labile spacer, as observed in cathepsin B enzymatic assays. Therefore, these results pave the way for the design of novel peptide conjugates to be used in pro-oxidant anticancer therapies.
Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Sistemas de Liberação de Medicamentos , Compostos Organometálicos/farmacologia , Aminopiridinas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-AtividadeRESUMO
AIM: Aim of the present study was to evaluate the usefulness of 11C-choline PET/CT for detecting lymphatic or haematogenous spread and for planning radiotherapy in patients with medium-to-high risk prostate cancer. METHODS: We have included 61 consecutive patients recently diagnosed with cancer prostate by biopsy. All patients were classified as medium-to-high risk: Gleason: 7-9; PSA: 6.3-30.4 ng/mL; stage T2c (N.=20) or stage T3 (N.=41). Image acquisition began 5 min after intravenous injection of 11C-choline (656+119 MBq), starting at the pelvis and continuing craniocaudally. Images were interpreted visually to evaluate uptake by the prostate gland. Lymph nodes with 11C-choline uptake were considered invaded, regardless of their size. Bone lesions were considered positive when they showed greater focal uptake than the surrounding bone. In patients with evidence of lymph-node invasion or bone metastases (15 patients), disease was classified as locoregional, oligometastatic, or multimetastatic. RESULTS: All patients had prostate gland uptake (20 focal, 8 bifocal, and 33 multifocal). Extraprostatic disease was present in 15 patients (24.6%), as follows: 9 (60%) in a single location: in an infradiaphragmatic lymph node (N.=6), in a supradiaphragmatic lymph node (N.=1), and in bone (M1) (N.=2). Six (40%) as multifocal invasion: with both infra- and supradiaphragmatic lymph node involvement (N.=2); with infradiaphragmatic lymph node involvement and M1 bone metastases (N.=3); and infra- and supradiaphragmatic lymph node involvement plus M1 bone metastases (N.=1). Disease was classified as locoregional (N.=6), oligometastatic (N.=5), and multimetastatic (N.=4). The 11 (73.3%) patients with locoregional and oligometastatic disease were selected to undergo intensity-modulated radiation therapy with dose escalation based on the PET findings. CONCLUSION: Our results suggest that 11C-choline PET/CT is a useful one-stop diagnostic procedure for evaluating patients with medium/high risk prostate cancer scheduled for radical treatment. 11C-choline PET/CT can reliably rule out lymph node involvement and remote metastases, allowing to select candidates for radiotherapy and to plan their treatment.
Assuntos
Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos/química , Planejamento da Radioterapia Assistida por Computador , Idoso , Biópsia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Radioisótopos de Carbono/química , Colina/química , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Diagnostic imaging is essential to assess the lame patient; lesions of the elbow joint have traditionally been evaluated radiographically, however computed tomography (CT) has been suggested as a useful technique to diagnose various elbow pathologies. The primary objective of this study was to determine the sensitivity and specificity of CT to assess medial coronoid disease (MCD), using arthroscopy as gold standard. The secondary objective was to ascertain the radiographic sensitivity and specificity for MCD compared with CT. METHODS: For this study 180 elbow joints were assessed, of which 141 had been examined with radiography, CT and arthroscopy; and 39 joints, had radiographic and CT assessment. Sensitivity and specificity were calculated for CT and radiographic findings using available statistical software. RESULTS: Sensitivity and specificity of CT using arthroscopy as gold standard resulted in high values for sensitivity (100 %) and specificity (93 %) for the assessment of MCD. For the radiographic evaluation, a sensitivity of 98 % and specificity of 64 - 69 % using CT as the technique of reference, were found. DISCUSSION: These results suggest that in case of doubt during radiographic assessment, CT could be used as a non-invasive technique to assess the presence of MCD. CONCLUSION: Based on the high sensitivity and specificity obtained in this study it has been considered that CT, rather than arthroscopy, is the preferred noninvasive technique to assess MCD lesions of the canine elbow joint.
Assuntos
Doenças do Cão/diagnóstico , Artropatias/veterinária , Coxeadura Animal/diagnóstico , Ulna/patologia , Animais , Artrografia/veterinária , Artroscopia/veterinária , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Membro Anterior/diagnóstico por imagem , Membro Anterior/patologia , Artropatias/diagnóstico , Artropatias/diagnóstico por imagem , Articulações/patologia , Coxeadura Animal/diagnóstico por imagem , Masculino , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/veterinária , Ulna/diagnóstico por imagemRESUMO
BACKGROUND/RATIONALE: Many interpersonal labor disputes stem from the lack of communication skills and the relational problems in the interactions between health professionals. AIMS/METHODS: A qualitative study was conducted in a Spanish hospital in order to get to know how the communicative interaction between hospital nurses is like in relation to the nurses' interpersonal interaction and communication skills developed in their working relationships. Twenty-one hospital nurses between 29 and 55 years old, working in different wards, were interviewed. Open-ended interview discourses were transcribed verbatim and analyzed using qualitative content analysis. RESULTS: The following four key themes were analyzed: communication and sender; communication and awareness of who has the problem; non-verbal communication; communication and recipient. CONCLUSION: The results of this study highlight the need to broaden nurses' relational-communication skills in order to increase job satisfaction.