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Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.
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INTRODUCTION/BACKGROUND: Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2-negative (HER2-) breast cancer is the most common subtype, predominantly treated with endocrine therapy. The efficacy of CDK4/6 inhibitors combined with endocrine therapy in this context remains to be fully evaluated. MATERIALS (OR PATIENTS) AND METHODS: This study compared the effectiveness of CDK4/6 inhibitors (palbociclib and ribociclib) in combination with an aromatase inhibitor or fulvestrant against endocrine therapy alone in patients with HR+/HER2- advanced breast cancer. The main focus was on progression-free survival (PFS) and overall survival (OS). The study involved a population treated exclusively with endocrine therapy for bone involvement, examining median OS and PFS, and adjusting for variables like stage, visceral metastasis, age, and treatment line. RESULTS: The study found no significant OS difference between treatments with palbociclib, ribociclib, and endocrine therapy alone. However, ribociclib combined with letrozole significantly improved PFS over letrozole alone. Propensity score weighting indicated a potential 50 % reduction in death risk with ribociclib compared to palbociclib, though this was not confirmed by cox regression. CONCLUSION: CDK4/6 inhibitors, particularly ribociclib in combination with letrozole, show promise in improving outcomes for HR+/HER2- breast cancer patients. While palbociclib may not be superior to traditional endocrine therapy, the results underscore the need for further research. These findings could influence future treatment protocols, emphasizing the importance of personalized therapy in this patient group.
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Certain naturally occurring volatile organic compounds are able to mitigate food spoilage caused by microbial growth. Their considerable vapor pressure enables them to create an antimicrobial atmosphere within a package, and this property can be used for the development of active food-packaging technologies. The volatility of these molecules, however, makes their stabilization difficult and limits their effectiveness. Whilst much research is being undertaken on the use of natural antimicrobial volatiles for inhibiting microbial growth in food, less attention has been paid to the design of controlled-release mechanisms that permit the efficient application of these compounds. Most studies to date either spray the volatile directly onto the fresh product, immerse it in a solution containing the volatile, or embed the volatile in a paper disc to create a vapor in the headspace of a package. More sophisticated alternatives would be delivery systems for the sustained release of volatiles into the package headspace. Such systems are based on the encapsulation of a volatile in organic or inorganic matrices (cyclodextrins, electrospun non-wovens, polymer films, micelles, molecular frameworks, etc.). However, most of these devices lack an efficient triggering mechanism for the release of the volatile; most are activated by humidity. All of these techniques are revised in the present work, and the most recent and innovative methods for entrapping and releasing volatiles based on reversible covalent bonds are also discussed.
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Introduction: An increasing aggressiveness in cancer treatment at the end of life (EoL) has been reported in several, but not all, countries. This study aimed to see how aggressive cancer treatment is at the EoL in an oncology center. Methods: Retrospective study of patients 18 years or older with a solid cancer diagnosis who died in 2017. The focus was systemic anticancer therapy (SACT), excluding hormonotherapy. Results: In 2017, 2024 patients with solid tumors died. Of those patients, 1262 (62%) were male, and the median age was 69 (range 19-97) years. The most frequent primary cancer was lung cancer, followed by colorectal and stomach cancers, and 740 (37%) patients had metastatic disease. The median interval between SACT and death was 61 days. Of the patients undergoing SACT, 216 (27%) did it in the last month of life, 174 (22%) between 8 and 30 days from death, and 42 (5%) in the last week. On multivariable analysis, head and neck, colorectal, breast, and melanoma primaries; age group (older than 65 years); and metastatic disease had statistical significance associated with SACT. Of these variables, only metastatic disease is more likely to undergo SACT. Conclusion: This study confirms the relatively frequent aggressiveness in cancer treatment at the EoL. Taking into consideration previously published data, it can be tentatively concluded that the use of SACT increased in the last month and the last week of life.
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Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.
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In 2020, female breast cancer was the most commonly diagnosed cancer worldwide, representing the type of cancer with the highest incidence among women and the second most common cause of cancer death among women in all OECD countries. The conventional measures addressing the burden of breast cancer by measuring mortality, incidence, and survival do not entirely reflect the quality of life and patients experience when receiving breast cancer care. The main objective of this study is to capture patient-reported outcomes and experiences in women with breast cancer in Portugal using methods developed for international benchmarking purposes, such as the OECD Patient-reported Indicators Surveys. The study included 378 women with breast cancer, with the age distribution being 19.8% aged 15 to 49 years and 80.2% aged 50 years and over. The data collection procedure and analysis followed the "OECD Breast Cancer Patient Reported Outcomes Working Group" protocol, allowing subsequent comparability with data from other OECD member countries. Most women were satisfied with the treatment outcome regarding the shape of their lumpectomy breast when wearing a bra (96.1%) and with the equal size of both breasts (78.3%). Findings on the WHO QOL-BREF showed that women manifest a lower score in well-being when compared with the general population or populations living with chronic diseases. This study shows the feasibility of implementing and using patient-reported metrics (PROM and PREM) in breast cancer services in Portugal. Measuring PROMs and PREMs from Portuguese women receiving breast cancer care provides insightful evidence into the quality and value of cancer care.
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Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Anciano , Calidad de Vida , Portugal , Medición de Resultados Informados por el Paciente , Encuestas y CuestionariosRESUMEN
Real world effectiveness, toxicity and costs analyses from chimeric antigen receptor (CAR)-T cell therapy are of utmost relevance to determine whether and how to offer patients highly personalized immunotherapy. In this study, we aimed at describing CAR T-cells effectiveness, safety and costs in a Portuguese Comprehensive Cancer Center. We performed a retrospective descriptive study of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma referred to CAR T-cell therapy, between May 2019 and February 2021. Rates of treatment response, toxicity and survival (Kaplan-Meier method) were analyzed by intention-to-treat. Direct medical costs stratified by inpatient-care, outpatient-care, and diagnostic-therapeutic procedures (DTP) were derived based on resources used and their respective unit costs. In twenty patients (median age 49.5y; 55%male; 70%DLBCL; 50% with primary refractory disease), best overall and complete response rates were 65.0% and 45.0%, respectively. Median overall (OS) and progression-free survivals were 9.2 and 7.3 months; 12-month OS rate was 42.6% (95%CI:23.2-78.3). Grade≥3 cytokine release syndrome and neurotoxicity occurred in 5.6% and 11.1% of patients, respectively. CAR T-cell therapy expenditure, including adverse events costs, was 7 176 196, or 286 238 when excluding drug cost. Median cost for treated patient was 355 165 with CAR T-cell drug cost accounting for 97.0% of the overall expense. Excluding CAR T-cell acquisition cost, inpatient-care and DTP accounted for 57% and 38% of total cost/patient, respectively. Our findings highlight the heavy economic burden of CAR T-cell therapy driven by drug acquisition costs.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos/uso terapéutico , Antígenos CD19 , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Background Epithelial growth factor receptor inhibitors (EGFRi) and bevacizumab are the two main target therapies available for first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC). However, the optimal sequencing of these agents remains unclear. In this study, we aimed to evaluate the optimal sequence with EGFRi and bevacizumab in first- and second-line treatment. Methods This was a retrospective cohort study with RAS wt mCRC patients identified by extended RAS analysis between 2013 and 2020 at a comprehensive cancer center. All patients had to be treated with a sequence of systemic treatment that included an EGFRi and bevacizumab in first and second line, in either order. Two groups were defined according to treatment sequence: first-line EGFRi followed by second-line bevacizumab (cohort A) or the reverse sequence (cohort B). Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival with first-line treatment (PFS1), progression-free survival with second-line treatment (PFS2), objective response rate (ORR), and serious adverse events (grade ≥ 3). Survival was estimated using the Kaplan-Meier method, and survival differences between groups were compared using the log-rank test. Univariate analyses were performed using Cox proportional hazard model. Results A total of 124 patients were included (93 in cohort A and 31 in cohort B). There were no statistical significant differences in median OS (A: 34.9 months vs B: 29.2 months; p=0.590), PFS1 (A: 13.1 months vs B: 8.2 months; p=0.600), and PFS2 (A: 7.4 months vs B: 5.5 months; p=0.110) between groups. No significant differences were also found between treatment sequences in subgroups defined by age, gender, primary tumor location, sidedness, timing of metastasis, number of metastatic sites, multimodal therapy, primary tumor resection, and first-line chemotherapy backbone. ORR was significantly higher with first-line treatment with EGFRi (A: 55.9% vs B: 22.6%; p=0.001). At the final follow-up, the proportion of patients with SAEs was similar between treatment sequences (p=0.827). Discussion Our study showed no impact of the treatment sequence with EGFRi and bevacizumab in the survival of RAS wt mCRC. However, patients treated with first-line EGFRi had significantly higher response rates, thus favoring its use in patients with symptomatic tumors and borderline resectable metastasis. Prospective trials are warranted to define the optimal sequence of treatment in RAS wt mCRC patients.
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Recent advancements in 3D in vitro culture have allowed for the development of cancer tissue models which accurately recapitulate the tumour microenvironment. Consequently, there has been increased innovation in therapeutic drug screening. While organoid cultures show great potential, they are limited by the time scale of their growth in vitro and the dependence upon commercial matrices, such as Matrigel, which do not allow for manipulations of their composition or mechanical properties. Here, we show a straightforward approach for the isolation and culture of primary human renal carcinoma cells and matched non-affected kidney. This approach does not require any specific selection for cancer cells, and allows for their direct culture in amenable 3D collagen-based matrices, with the preservation of cancer cells as confirmed by NGS sequencing. This method allows for culture of patient-derived cancer cells in 3D microenvironment, which can be used for downstream experimentation such as investigation of cell-matrix interaction or drug screening.
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BACKGROUND: Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20-25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC). METHODS: Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012-2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015-2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed. RESULTS: AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375, with pertuzumab accounting for 13,978 (24.79%) and increasing in 15,982 the average cost/patient (p < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370 per percentage point of pCR. CONCLUSIONS: ICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.
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OBJECTIVE: We aim to describe treatment patterns and overall survival (OS) among a Portuguese cohort of patients with small cell lung cancer (SCLC). METHODS: This study utilised a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with SCLC at IPO-Porto between January 2012 and June 2017, with follow-up to December 2017, were included. Patients were stratified into subgroups with limited disease (LD) or extensive disease (ED). Treatment analyses were performed from 2015 onwards. RESULTS: Overall, 227 patients diagnosed with SCLC (37 LD; 190 ED) were analysed. Median OS (interquartile range [IQR]) was 15.0 months (3.8-39.3) for LD-SCLC and 5.0 months (1.7-10.3) for ED-SCLC. Among 19 patients diagnosed with LD-SCLC from 2015 onwards, 12 (63.2%) received initial treatment with systemic anticancer therapy (SACT) ± radiotherapy; 6 (31.6%) received best supportive care (BSC). Among 89 patients with ED-SCLC, 57 (68.5%) received SACT ± palliative radiotherapy; 28 (31.5%) received BSC. For patients receiving platinum doublet chemotherapy (±radiotherapy), median OS (IQR) was not reached for LD-SCLC and 5.4 months (2.3-10.9) for ED-SCLC. CONCLUSION: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for patients diagnosed with SCLC, particularly those with ED, and highlights a need for more effective therapies.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Portugal , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológicoRESUMEN
AIM: This observational study evaluated treatment patterns and survival for patients with stage I-IIIA non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: Adults newly diagnosed with NSCLC in 2012-2016 at IPO-Porto hospital were included. Treatment data were available for patients diagnosed in 2015-2016. RESULTS: 495 patients were included (median age: 67 years). The most common treatments were surgery alone or with another therapy (stage I: 66%) and systemic anticancer therapy plus radiotherapy (stage II: 54%; stage IIIA: 59%). One-year OS (95% CI) for patients with stage I, II and IIIA NSCLC (diagnosed 2012-2016) were 92% (88-96), 71% (62-82) and 69% (63-75), respectively; one-year OS (95% CI) for treated patients with stage I-II or stage IIIA NSCLC (diagnosed 2015-2016) were 89% (81-97) and 86% (75-98) for non-squamous cell and 76% (60-95) and 49% (34-70) for squamous cell NSCLC. CONCLUSION: Treatment advances are strongly needed for stage I-IIIA NSCLC, especially for patients with squamous cell histology.
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BACKGROUND: This paper fills a gap in the applied research field, for a local context, by addressing the topics of describing cataract surgery' clinical outcomes; quality of life (QoL); and costs of the patients treated after the implementation of the ICHOM standard set. METHODS: This is a retrospective observational study using real-world data (RWD). We included all patients subjected to cataract surgery at the Portuguese Institute of oncology - Porto (IPO-Porto), Portugal, after 3 months follow up period completed between 5th June 2017 and 21st May 2018. The following inclusion criteria: corrected visual acuity of ≤ 6/10 or other significant visual disturbance due to lens opacity or the existence of a large anisometropia. A circuit was implemented based on the ICHOM standard for cataract, to measure clinical variables (e.g. visual acuity) and QoL (CATQUEST-9SF) before and after surgery, and cost of treatment. The results were explored by means of a paired-sample t-test, considering normality assumptions. RESULTS: Data refers to 268 patients (73 P25-P75:32-95 years old), regarding 374 eyes. The cataract surgery had a positive effect on visual acuity (p < 0.001), refraction (right and left cylinder; p < 0.001) and all QoL dimensions. The vast majority of patients, around 98%, reported improvements in QoL. Based on IPO-Porto administrative records, the direct cost of treating cataracts (per eye) is of 500, representing a total cost of 187,000 for the number of patients operated herein. CONCLUSION: This study reports the successful implementation of the ICHOM standard set for cataracts in a Portuguese institution and confirms that cataract surgery provides a rapid visual recovery, with excellent visual outcomes and minimal complications in most patients, while also having a positive impact on patients' quality of life.
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Extracción de Catarata , Catarata , Adulto , Anciano , Anciano de 80 o más Años , Catarata/complicaciones , Humanos , Persona de Mediana Edad , Portugal , Calidad de Vida , Agudeza VisualRESUMEN
BACKGROUND: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal. METHODS: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models. RESULTS: Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ. CONCLUSIONS: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Femenino , Humanos , Inmunoterapia , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Portugal/epidemiología , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more 'resistant' CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.
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The objective of this study was to examine the effect of Mindkeys Training, a mindfulness-based educational intervention, on attention, self-control, and aggressiveness in third-year primary school pupils. In order to achieve this aim, a switching replications design was used. Two groups of third year primary students (nGE1 = 40; nGE2 = 33), aged between 7 and 10 years old (M = 8.08; DT = 0.49), had the intervention at different time points, such that while one served as the experimental group, the other served as the control group. Longitudinal differences were examined in both groups, and cross-sectional differences were examined between the two groups at three time points; at the start of the study, and following the intervention with each group. To that end, measurements of problems of attention, deficits of self-control, and aggressiveness for students were obtained via a teacher rating scale. The intervention program demonstrated a positive effect on the reduction of pupils' attention problems, deficits of self-control, and aggressiveness. The effects were greater on the cognitive variables that the intervention worked on directly (attention and self-control). Attention was the variable on which the intervention exhibited the longest term effects.
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Atención , Atención Plena , Autocontrol , Estudiantes , Niño , Estudios Transversales , Humanos , Instituciones Académicas , Estudiantes/psicologíaRESUMEN
Despite being considered present in most vascularised tissues, lymphatic vessels have not been properly shown in human adipose tissue (AT). Our goal in this study is to investigate an unanswered question in AT biology, regarding lymphatic network presence in tissue parenchyma. Using human subcutaneous (S-) and visceral (V-) AT samples with whole mount staining for lymphatic specific markers and three-dimensional imaging, we showed lymphatic capillaries and larger lymphatic vessels in the human VAT. Conversely, in the human SAT, microcirculatory lymphatic vascular structures were rarely detected and no initial lymphatics were found.
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Tejido Adiposo/anatomía & histología , Vasos Linfáticos/anatomía & histología , Tejido Adiposo/irrigación sanguínea , Tejido Adiposo/fisiología , Femenino , Humanos , Imagenología Tridimensional , Inmunohistoquímica , Grasa Intraabdominal/anatomía & histología , Grasa Intraabdominal/irrigación sanguínea , Grasa Intraabdominal/fisiología , Vasos Linfáticos/irrigación sanguínea , Vasos Linfáticos/fisiología , Masculino , Persona de Mediana Edad , Grasa Subcutánea/anatomía & histología , Grasa Subcutánea/irrigación sanguínea , Grasa Subcutánea/fisiologíaRESUMEN
Purpose: Home-time (the number of days spent at home during the first 3 months after stroke) shows a strong association with the modified Rankin scale (mRS). We studied whether Home-time was also a determinant of quality-of-life and medical care costs after ischemic stroke, and assessed factors delaying discharge home.Materials and methods: Five hundred and sixty nine patients participated in a retrospective study when returning for an in-person visit after an ischemic stroke. Home-time, mRS, EQ-5D-3L, inpatient and outpatient resource utilization, use of mobility aids, changes to home and car, comorbidities were recorded.Results: Each additional Home-time day was significantly associated with an increase in utility of 0.0056 (p < 0.0001) and an in- and outpatient cost saving of $99 (p = 0.0158). Requiring extra material support significantly decreased Home-time by 76 days (including: requiring home changes: -68 days, car alterations: -49 days, needing a wheelchair: -80 days or walker: -71 days, needing bed or bath rails: -79 days). This univariable effect was confirmed in multivariable analysis when comparing with patients having the same disability level without requiring material support.Conclusions: Home-time is a stroke outcome associated with disease severity, healthcare costs and patient wellbeing. Streamlining the discharge process for those requiring extra material support may lead to cost savings and higher quality-of-life.Implications for rehabilitationDelays in discharge from the acute hospital or rehabilitation facility are incurred when patients need extra material support in order to return home.Staff from the discharging facility should assist families by giving timely information on the availability and the cost of wheel chairs and walkers; and explaining and planning the need of a stair lift, bed and bath rails as well as car modifications.Planning the discharge process with the families will lead to a more rapid return home and will result in reduced overall health care costs and higher quality of life for the patients.
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Personas con Discapacidad , Atención Domiciliaria de Salud , Accidente Cerebrovascular Isquémico , Calidad de Vida , Rehabilitación de Accidente Cerebrovascular , Anciano , Comorbilidad , Evaluación de la Discapacidad , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Atención Domiciliaria de Salud/métodos , Atención Domiciliaria de Salud/organización & administración , Atención Domiciliaria de Salud/estadística & datos numéricos , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Rehabilitación de Accidente Cerebrovascular/economía , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/psicología , Rehabilitación de Accidente Cerebrovascular/estadística & datos numéricos , Transporte de Pacientes/métodosRESUMEN
INTRODUCTION: 'Personalised medicine' aims to tailor interventions to the individual, and has become one of the fastest growing areas of cancer research. One of these approaches is to harvest cancer cells from patients and grow them in the laboratory, which can then be subjected to treatments and the response assessed. We have developed a 3D tumour model with a complex protein matrix that mimics the tumour stroma, cell to cell and cell-matrix interactions seen in vivo, called a tumouroid. In this study, we test the acceptability and feasibility of using this model to establish patient-derived tumouroids. METHODS AND ANALYSIS: This is a first in-human study using prospective tissue and data collection of adult participants with confirmed or suspected renal cell carcinoma. The goals of the study are to assess patient acceptability to the use of patient-derived tumour models for future treatment decisions, and to assess the feasibility of generating patient-specific renal cancer tumouroids that can be challenged with drugs. These goals will be realised through the collection of tumour samples (expected nâ¯=â¯10), participant-completed questionnaires (expected nâ¯=â¯10), and in-depth semi-structured interviews with patients (expected nâ¯=â¯5). Collected multiregional tumour samples will be dissociated to isolate primary cells which are then expanded in vitro and incorporated into tumouroids. Drug challenge will ensue and the response will be categorised into "responder", "weak responder", and "non-responder". Statistical analysis will be descriptive. ETHICS AND DISSEMINATION: The study has ethical approval (REC reference 17/LO/1744). Findings will be made available to patients, clinicians, funders, and the National Health Service (NHS) through presentations at national and international meetings, peer-reviewed publications, social media and patient support groups. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (NCT03300102).
RESUMEN
Patients with skin cancer should be treated in healthcare units that ensure holistic and multidisciplinary approaches. Current healthcare units, especially those dedicated to cancer care, must evolve to integrated patient-centred systems. The current review presents a holistic health services perspective towards managing patients with melanoma of the skin, based on a literature search. It includes a detailed discussion on how this could impact on the patient, his or her quality of life and on service providers. Data from a multidisciplinary integrated practice unit, specialised in skin cancer, were also discussed, namely, for outcomes measurements, access to innovative treatments, value-based healthcare, patient centricity and use of integrated systems. Epidemiology data, including disease determinants and risk factors, play an important role in defining measures, resources and management of these integrated cancer units. To optimise effective care and improve survival outcomes, integrated cancer clinics should comprise, in a patient-centred way, innovative treatments and technologies, along with continuous training and creation of multidisciplinary units of healthcare professionals. Measurement of outcomes, such as clinical, quality of life and cost, is decisive in determining affordability and access to the best available state-of-the-art care. Besides, treatment of melanoma has significantly improved over recent years, but with increasing costs, which brings a challenging mission to guarantee access to treatment and quality care. Value-based healthcare allows the achievement of better health outcomes and higher quality services while reducing the costs associated with the full-care cycle. Therefore, current healthcare systems should develop in line with health institutions' organisation and culture, increasing adherence to best practices and create value.