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1.
Nutr Cancer ; 76(5): 442-451, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486410

RESUMEN

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.


Asunto(s)
Supervivientes de Cáncer , Neoplasias Esofágicas , Desnutrición , Neoplasias Gástricas , Humanos , Masculino , Estados Unidos , Persona de Mediana Edad , Anciano , Femenino , Calidad de Vida , Estudios Prospectivos , Estudios Transversales , Neoplasias Esofágicas/cirugía , Neoplasias Gástricas/cirugía , Ingestión de Alimentos , Desnutrición/etiología , Dieta , Factores de Riesgo
2.
Surgeon ; 22(3): 143-149, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38693029

RESUMEN

INTRODUCTION: Surgeons are at high risk of developing musculoskeletal symptoms due to a range of factors including, maladaptive positioning and surgical ergonomics. Cervical muscle strain and biomechanical load is most prevalent due to repetitive motions and prolonged static neck positioning. This issue is apparent through reports of prevalence between 10 and 74.4% among surgeons. The aim of this systematic review is to provide an objective assessment of the clinical evidence available and a descriptive analysis of the effects of kinematics and surgical ergonomics on the prevalence of surgeons' cervical musculoskeletal pain. METHODS: This is PRISMA-compliant systematic review of clinical studies assessing the prevalence of cervical musculoskeletal dysfunction in surgeons by searching PUBMED and Ovid EMBASE databases from inception to 19th October 2023. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: A total of 9 studies were included in the final qualitative analysis. The use of loupes, open surgery and excessive neck flexion (>30°) were associated with cervical dysfunction. Comparison of study outcomes was challenging due to heterogeneity within study methods and the paucity of methodological quality. CONCLUSION: The current literature assessing ergonomic and biomechanical factors predisposing surgeons to cervical musculoskeletal dysfunction is insufficient to provide reliable guidance for clinicians. Although the literature identifies factors contributing to work-related cervical dysfunction, few attempt to evaluate interventions for improved surgical ergonomics. An objective assessment of interventions that prompt postural correction with the aim to improve neck pain in surgeon cohorts is warranted.


Asunto(s)
Ergonomía , Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Cirujanos , Humanos , Enfermedades Profesionales/etiología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/fisiopatología , Fenómenos Biomecánicos , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/epidemiología , Dolor de Cuello/etiología , Dolor de Cuello/epidemiología , Dolor de Cuello/fisiopatología , Factores de Riesgo , Postura/fisiología
3.
J Autoimmun ; 138: 103046, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37229810

RESUMEN

Juvenile idiopathic arthritis (JIA) is an autoimmune, inflammatory joint disease with complex genetic etiology. Previous GWAS have found many genetic loci associated with JIA. However, the biological mechanism behind JIA remains unknown mainly because most risk loci are located in non-coding genetic regions. Interestingly, increasing evidence has found that regulatory elements in the non-coding regions can regulate the expression of distant target genes through spatial (physical) interactions. Here, we used information on the 3D genome organization (Hi-C data) to identify target genes that physically interact with SNPs within JIA risk loci. Subsequent analysis of these SNP-gene pairs using data from tissue and immune cell type-specific expression quantitative trait loci (eQTL) databases allowed the identification of risk loci that regulate the expression of their target genes. In total, we identified 59 JIA-risk loci that regulate the expression of 210 target genes across diverse tissues and immune cell types. Functional annotation of spatial eQTLs within JIA risk loci identified significant overlap with gene regulatory elements (i.e., enhancers and transcription factor binding sites). We found target genes involved in immune-related pathways such as antigen processing and presentation (e.g., ERAP2, HLA class I and II), the release of pro-inflammatory cytokines (e.g., LTBR, TYK2), proliferation and differentiation of specific immune cell types (e.g., AURKA in Th17 cells), and genes involved in physiological mechanisms related to pathological joint inflammation (e.g., LRG1 in arteries). Notably, many of the tissues where JIA-risk loci act as spatial eQTLs are not classically considered central to JIA pathology. Overall, our findings highlight the potential tissue and immune cell type-specific regulatory changes contributing to JIA pathogenesis. Future integration of our data with clinical studies can contribute to the development of improved JIA therapy.


Asunto(s)
Artritis Juvenil , Humanos , Artritis Juvenil/genética , Regulación de la Expresión Génica , Sitios de Carácter Cuantitativo , Diferenciación Celular , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Aminopeptidasas/genética
4.
Surgeon ; 21(3): e118-e125, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35525818

RESUMEN

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.


Asunto(s)
Neoplasias de Cabeza y Cuello , Procedimientos de Cirugía Plástica , Humanos , Colgajos Quirúrgicos , Mandíbula/cirugía , Neoplasias de Cabeza y Cuello/cirugía
5.
Br J Neurosurg ; 37(3): 329-333, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32202165

RESUMEN

Benign cysts within the pure aqueductal region are a rare entity. Their critical location within the ventricular system presents a risk of potentially catastrophic outcomes. We present a case of a 68-year-old female who was transferred to our unit with an acute obstructive triventricular hydrocephalus caused by a benign cyst within the cerebral aqueduct. She became unconscious and had an urgent endoscopic third ventriculostomy (ETV). Post-operatively, the patient was recovering well but then developed a sudden onset severe headache accompanied by vomiting. Imaging revealed intracystic haemorrhage with expansion of lesion but there was no obstructive hydrocephalus due to CSF diversion performed 9 d prior. She was treated conservatively and continued to improve.


Asunto(s)
Quistes , Hidrocefalia , Neuroendoscopía , Tercer Ventrículo , Femenino , Humanos , Anciano , Acueducto del Mesencéfalo/diagnóstico por imagen , Acueducto del Mesencéfalo/cirugía , Tercer Ventrículo/cirugía , Ventrículos Cerebrales/cirugía , Ventriculostomía/efectos adversos , Ventriculostomía/métodos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/cirugía , Quistes/cirugía , Resultado del Tratamiento , Neuroendoscopía/efectos adversos
6.
Dig Dis Sci ; 67(12): 5540-5550, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35288829

RESUMEN

BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.


Asunto(s)
Colitis Ulcerosa , Humanos , Femenino , Persona de Mediana Edad , Masculino , Colitis Ulcerosa/patología , Interleucina-17 , Interleucina-2/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral , Progresión de la Enfermedad
7.
Surgeon ; 20(2): 67-70, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33414044

RESUMEN

BACKGROUND: The games of hurling and camogie involve fast ball movement and a substantial physical contact with opposing players. The wearing of protective helmets with faceguards became obligatory 10 years ago and resulted in a significant reduction of craniofacial injuries. However since then a trend has emerged of players modifying helmets to improve comfort and vision. As officials are not yet required to perform pre-match checks, many players enter competition with defective protective equipment which poses a risk to both themselves and others. METHODS: We present 4 cases of penetrating upper limb injury in hurlers sustained as a result of helmet faceguards. These injuries were sustained during competitive play and the affected patients presented with portions of the faceguards embedded in their wounds. Each patient required admission to hospital and exploration of their wounds under general anaesthetic. CONCLUSIONS: This case series demonstrates the dangers of modification and damage to protective helmet faceguards used in hurling and camogie. We encourage helmet manufacturers to re-engage with players to ensure that current safety equipment meets the functional demands of the modern player while adhering to approved manufacturing standards. Mandatory helmet checks before competitive games would reduce the likelihood of penetrating upper limb injury to players.


Asunto(s)
Traumatismos en Atletas , Dispositivos de Protección de la Cabeza , Extremidad Superior , Traumatismos en Atletas/etiología , Dispositivos de Protección de la Cabeza/efectos adversos , Humanos , Extremidad Superior/lesiones
8.
Anal Biochem ; 613: 113980, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33065116

RESUMEN

Fat soluble vitamers (FSV) are several biochemically diverse micronutrients essential for healthy development, growth, metabolism, and cell regulation. We cannot synthesize FSV completely or at the required concentrations. Deficiency or excess of FSV can result in many health problems. Plasma is the most accessible sample matrix for the quantification of FSV. However, due to its complexity and other analytical challenges (e.g., FSV sensitivity to light, oxygen, heat, pH, chemical heterogeneity, standard availability), developing a method for the simultaneous quantification of multiple FSV at physiological concentrations has been challenging. In this systematic review, we examine the parameters and criteria used in existing Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) methods for FSV quantification to the extraction method, chromatographic resolution, matrix effects, and method validation as critical to a sensitive and robust method. We conclude that the final FSV method sensitivity is predominantly based on aforementioned criteria and future method development using LC-MS/MS will benefit from the application of this systematic review.


Asunto(s)
Espectrometría de Masas en Tándem/métodos , Vitaminas/análisis , Animales , Fraccionamiento Químico/métodos , Cromatografía Líquida de Alta Presión , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Solubilidad , Vitaminas/sangre , Vitaminas/química
9.
J Appl Microbiol ; 131(5): 2223-2234, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33876507

RESUMEN

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.


Asunto(s)
Bacteriocinas , Lactococcus lactis , Nisina , Antibacterianos/farmacología , Nisina/genética , Nisina/farmacología , Staphylococcus/genética , Streptococcus , Streptococcus agalactiae
10.
Phys Rev Lett ; 125(21): 210505, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33274991

RESUMEN

We report long coherence times (up to 300 ms) for near-surface bismuth donor electron spins in silicon coupled to a superconducting microresonator, biased at a clock transition. This enables us to demonstrate the partial absorption of a train of weak microwave fields in the spin ensemble, their storage for 100 ms, and their retrieval, using a Hahn-echo-like protocol. Phase coherence and quantum statistics are preserved in the storage.

11.
Ann Oncol ; 30(11): 1728-1739, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31418764

RESUMEN

Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.


Asunto(s)
Partículas alfa/uso terapéutico , Antígeno Prostático Específico/antagonistas & inhibidores , Neoplasias de la Próstata/terapia , Radioinmunoterapia/métodos , Radiofármacos/uso terapéutico , Actinio , Ensayos Clínicos Fase III como Asunto , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/farmacología , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , Masculino , Medicina de Precisión/métodos , Supervivencia sin Progresión , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Radioinmunoterapia/efectos adversos , Radiofármacos/farmacología , Planificación de la Radioterapia Asistida por Computador , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/efectos de la radiación
12.
Ann Oncol ; 30(12): 1992-2003, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31560068

RESUMEN

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Docetaxel/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Estudios Retrospectivos
13.
BMC Cancer ; 19(1): 682, 2019 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-31299920

RESUMEN

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.


Asunto(s)
Neoplasias Esofágicas/epidemiología , Esofagectomía/efectos adversos , Ejercicio Físico , Estado de Salud , Adulto , Anciano , Supervivientes de Cáncer , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vigilancia en Salud Pública , Calidad de Vida , Factores de Riesgo
14.
Ann Oncol ; 29(1): 215-222, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29045551

RESUMEN

Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods: A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS). Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.


Asunto(s)
Biopsia/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/genética , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo
15.
Ann Oncol ; 29(5): 1235-1248, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29529169

RESUMEN

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.


Asunto(s)
Acetato de Abiraterona/administración & dosificación , Antagonistas de Andrógenos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Acetato de Abiraterona/efectos adversos , Anciano , Antagonistas de Andrógenos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Supervivencia sin Enfermedad , Docetaxel/efectos adversos , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Metaanálisis en Red , Supervivencia sin Progresión , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Nivel de Atención
16.
Proc Biol Sci ; 285(1891)2018 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-30464064

RESUMEN

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.


Asunto(s)
Agricultura/tendencias , Participación de la Comunidad , Alimentos , Investigación/tendencias , Agricultura/normas , Investigación/normas , Estados Unidos
17.
Acta Oncol ; 57(7): 965-972, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29419331

RESUMEN

BACKGROUND: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. METHODS: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. FINDINGS: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. INTERPRETATION: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.


Asunto(s)
Fraccionamiento de la Dosis de Radiación , Neoplasias/radioterapia , Calidad de Vida , Compresión de la Médula Espinal/radioterapia , Anciano , Anciano de 80 o más Años , Estudios de Equivalencia como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/patología , Compresión de la Médula Espinal/etiología , Resultado del Tratamiento
18.
Support Care Cancer ; 26(8): 2615-2623, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29455302

RESUMEN

PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.


Asunto(s)
Terapia por Ejercicio/métodos , Modalidades de Fisioterapia/psicología , Neoplasias Gástricas/rehabilitación , Sobrevivientes/psicología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología
19.
Support Care Cancer ; 26(5): 1569-1576, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29197960

RESUMEN

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.


Asunto(s)
Neoplasias Esofágicas/complicaciones , Fuerza Muscular/fisiología , Terapia Neoadyuvante/efectos adversos , Rendimiento Físico Funcional , Sarcopenia/etiología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Sarcopenia/patología
20.
BMC Vet Res ; 14(1): 107, 2018 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-29558919

RESUMEN

BACKGROUND: Accelerometer-based technologies could be useful in providing objective measures of canine ambulation, but most are either not tailored to the idiosyncrasies of canine gait, or, use un-validated or closed source approaches. The aim of this paper was to validate algorithms which could be applied to accelerometer data for i) counting the number of steps and ii) distance travelled by a dog. To count steps, an approach based on partitioning acceleration was used. This was applied to accelerometer data from 13 dogs which were walked a set distance and filmed. Each footfall captured on video was annotated. In a second experiment, an approach based on signal features was used to estimate distance travelled. This was applied to accelerometer data from 10 dogs with osteoarthritis during normal walks with their owners where GPS (Global Positioning System) was also captured. Pearson's correlations and Bland Altman statistics were used to compare i) the number of steps measured on video footage and predicted by the algorithm and ii) the distance travelled estimated by GPS and predicted by the algorithm. RESULTS: Both step count and distance travelled could be estimated accurately by the algorithms presented in this paper: 4695 steps were annotated from the video and the pedometer was able to detect 91%. GPS logged a total of 20,184 m meters across all dogs; the mean difference between the predicted and GPS estimated walk length was 211 m and the mean similarity was 79%. CONCLUSIONS: The algorithms described show promise in detecting number of steps and distance travelled from an accelerometer. The approach for detecting steps might be advantageous to methods which estimate gross activity because these include energy output from stationary activities. The approach for estimating distance might be suited to replacing GPS in indoor environments or others with limited satellite signal. The algorithms also allow for temporal and spatial components of ambulation to be calculated. Temporal and spatial aspects of dog ambulation are clinical indicators which could be used for diagnosis or monitoring of certain diseases, or used to provide information in support of canine weight-loss programmes.


Asunto(s)
Acelerometría/veterinaria , Perros/fisiología , Acelerometría/instrumentación , Acelerometría/métodos , Algoritmos , Animales , Femenino , Masculino , Caminata/fisiología , Caminata/estadística & datos numéricos
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