RESUMEN
OBJECTIVE: Amiodarone (AMD), a drug of choice to treat cardiac arrhythmias, has a narrow therapeutic index (NTI). It inhibits CYP3A4, CYP2C9, and CYP2D6 enzymes. Quercetin (QUE), a pharmacologically important bioflavonoid in vegetables and fruits, is important in treating cardiovascular comorbidities. QUE alters the bioavailability of drugs used concurrently by dual inhibition of P-glycoproteins (P-gp) and cytochrome (CYP) enzyme systems. The current study aimed to investigate the pre-treatment and co-administration effect of QUE on AMD pharmacokinetics in rats. MATERIALS AND METHODS: Two separate animal trials (I and II) were planned to probe the effect of QUE on AMD pharmacokinetics by following previously cited studies. The pre-treatment group received oral doses of QUE for 14 days, and a single dose of AMD on the 15th day. Rats were administered single doses of QUE (20 mg/kg) and AMD (50 mg/kg) concurrently in a carboxymethylcellulose (CMC) in the co-administration study. Blood was collected at pre-determined time points. AMD was quantified by HPLC, and data was analyzed by PK solver software. RESULTS: In the pre-treated group, peak plasma concentration (Cmax) and area under the curve (AUC0-∞) of AMD were increased by 45.52% and 13.70%, respectively, while time to achieve maximum concentration (tmax), half-life (t1/2) and clearance (CL) were declined by 35.72%, 16.75%, and 11.0% respectively compared to the control. In the co-administered group, compared to controls, Cmax and AUC0-∞ were elevated to 12.90% and 7.80%, respectively, while tmax, t1/2, and CL declined by 16.70%, 2.35%, and 13.40%. Further, AMD was increased in lung tissue of both treated groups, relative to the respective controls. CONCLUSIONS: A notable pharmacokinetic drug interaction between QUE and AMD was observed in rats and warrants possible drug interaction study in humans, suggesting AMD dose adjustment specifically in patients with arrhythmia having a pre-treatment history and simultaneous administration of QUE-containing products.
Asunto(s)
Amiodarona , Quercetina , Humanos , Ratas , Animales , Quercetina/farmacología , Amiodarona/farmacología , Distribución Tisular , Interacciones Farmacológicas , Disponibilidad Biológica , Área Bajo la CurvaRESUMEN
Abstract Feral dogs are well-organized hunters of ungulates in many parts of the world, causing great damage to wildlife populations and ultimately to the ecosystem. In Pakistan, the impacts of feral dogs on the wildlife have not been documented yet. In a period of fifteen years (2006-2020), feral dogs have killed hundreds of threatened markhor in Chitral gol national park (CGNP), Pakistan. Despite direct predation other impacts including disturbance and competition with other natural predators, could compromise conservation and management efforts. The population of feral dogs seems to have been increased with the increase of dumping sites by communities. Our findings suggest that there are pressing needs of controlling the feral dogs population and eradicating them from the core zone of CGNP and surrounding buffer communities. Conventional culling of dogs should be coupled with modern techniques like castration and sterilization. Communities should be educated regarding the clean environment, proper disposal of home wastes and, biodiversity conservation.
Resumo Os cães ferozes são caçadores bem organizados de ungulados em muitas partes do mundo, causando grandes danos à população de animais selvagens e, em última instância, ao ecossistema. No Paquistão, os impactos dos cães selvagens na vida selvagem ainda não foram documentados. Em um período de 15 anos (2006-2020), cães selvagens mataram centenas de markhor ameaçados no parque nacional Chitral gol (CGNP), Paquistão. Apesar da predação direta, outros impactos, incluindo distúrbios e competições com outros predadores naturais podem comprometer os esforços de conservação e manejo. A população de cães selvagens parece ter aumentado com o aumento dos locais de despejo pelas comunidades. Nossas descobertas sugerem que há necessidades urgentes para controlar a população de cães selvagens e erradicá-los da zona central do CGNP e das comunidades-tampão vizinhas. O abate convencional de cães deve ser combinado com técnicas modernas como castração e esterilização. As comunidades devem ser educadas sobre o meio ambiente limpo, o descarte adequado de resíduos domésticos e a conservação da biodiversidade.
Asunto(s)
Animales , Perros , Ecosistema , Parques Recreativos , Pakistán , Cabras , Animales SalvajesRESUMEN
Feral dogs are well-organized hunters of ungulates in many parts of the world, causing great damage to wildlife populations and ultimately to the ecosystem. In Pakistan, the impacts of feral dogs on the wildlife have not been documented yet. In a period of fifteen years (2006-2020), feral dogs have killed hundreds of threatened markhor in Chitral gol national park (CGNP), Pakistan. Despite direct predation other impacts including disturbance and competition with other natural predators, could compromise conservation and management efforts. The population of feral dogs seems to have been increased with the increase of dumping sites by communities. Our findings suggest that there are pressing needs of controlling the feral dogs population and eradicating them from the core zone of CGNP and surrounding buffer communities. Conventional culling of dogs should be coupled with modern techniques like castration and sterilization. Communities should be educated regarding the clean environment, proper disposal of home wastes and, biodiversity conservation.
Os cães ferozes são caçadores bem organizados de ungulados em muitas partes do mundo, causando grandes danos à população de animais selvagens e, em última instância, ao ecossistema. No Paquistão, os impactos dos cães selvagens na vida selvagem ainda não foram documentados. Em um período de 15 anos (2006-2020), cães selvagens mataram centenas de markhor ameaçados no parque nacional Chitral gol (CGNP), Paquistão. Apesar da predação direta, outros impactos, incluindo distúrbios e competições com outros predadores naturais podem comprometer os esforços de conservação e manejo. A população de cães selvagens parece ter aumentado com o aumento dos locais de despejo pelas comunidades. Nossas descobertas sugerem que há necessidades urgentes para controlar a população de cães selvagens e erradicá-los da zona central do CGNP e das comunidades-tampão vizinhas. O abate convencional de cães deve ser combinado com técnicas modernas como castração e esterilização. As comunidades devem ser educadas sobre o meio ambiente limpo, o descarte adequado de resíduos domésticos e a conservação da biodiversidade.
Asunto(s)
Masculino , Femenino , Animales , Perros , Perros/crecimiento & desarrollo , Orquiectomía , Ovariectomía , Regulación de la Población/métodosRESUMEN
Abstract Feral dogs are well-organized hunters of ungulates in many parts of the world, causing great damage to wildlife populations and ultimately to the ecosystem. In Pakistan, the impacts of feral dogs on the wildlife have not been documented yet. In a period of fifteen years (2006-2020), feral dogs have killed hundreds of threatened markhor in Chitral gol national park (CGNP), Pakistan. Despite direct predation other impacts including disturbance and competition with other natural predators, could compromise conservation and management efforts. The population of feral dogs seems to have been increased with the increase of dumping sites by communities. Our findings suggest that there are pressing needs of controlling the feral dogs population and eradicating them from the core zone of CGNP and surrounding buffer communities. Conventional culling of dogs should be coupled with modern techniques like castration and sterilization. Communities should be educated regarding the clean environment, proper disposal of home wastes and, biodiversity conservation.
Resumo Os cães ferozes são caçadores bem organizados de ungulados em muitas partes do mundo, causando grandes danos à população de animais selvagens e, em última instância, ao ecossistema. No Paquistão, os impactos dos cães selvagens na vida selvagem ainda não foram documentados. Em um período de 15 anos (2006-2020), cães selvagens mataram centenas de markhor ameaçados no parque nacional Chitral gol (CGNP), Paquistão. Apesar da predação direta, outros impactos, incluindo distúrbios e competições com outros predadores naturais podem comprometer os esforços de conservação e manejo. A população de cães selvagens parece ter aumentado com o aumento dos locais de despejo pelas comunidades. Nossas descobertas sugerem que há necessidades urgentes para controlar a população de cães selvagens e erradicá-los da zona central do CGNP e das comunidades-tampão vizinhas. O abate convencional de cães deve ser combinado com técnicas modernas como castração e esterilização. As comunidades devem ser educadas sobre o meio ambiente limpo, o descarte adequado de resíduos domésticos e a conservação da biodiversidade.
RESUMEN
Feral dogs are well-organized hunters of ungulates in many parts of the world, causing great damage to wildlife populations and ultimately to the ecosystem. In Pakistan, the impacts of feral dogs on the wildlife have not been documented yet. In a period of fifteen years (2006-2020), feral dogs have killed hundreds of threatened markhor in Chitral gol national park (CGNP), Pakistan. Despite direct predation other impacts including disturbance and competition with other natural predators, could compromise conservation and management efforts. The population of feral dogs seems to have been increased with the increase of dumping sites by communities. Our findings suggest that there are pressing needs of controlling the feral dogs population and eradicating them from the core zone of CGNP and surrounding buffer communities. Conventional culling of dogs should be coupled with modern techniques like castration and sterilization. Communities should be educated regarding the clean environment, proper disposal of home wastes and, biodiversity conservation.
Asunto(s)
Ecosistema , Parques Recreativos , Animales , Animales Salvajes , Perros , Cabras , PakistánAsunto(s)
Infecciones por Coronavirus/complicaciones , Personal de Salud/estadística & datos numéricos , Neumonía Viral/complicaciones , Complicaciones Infecciosas del Embarazo/patología , Resultado del Embarazo , Adulto , Betacoronavirus/aislamiento & purificación , COVID-19 , Femenino , Humanos , Pandemias , Embarazo , SARS-CoV-2 , Adulto JovenAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Coronavirus , China , Humanos , SARS-CoV-2Asunto(s)
Infecciones por Coronavirus/prevención & control , Países en Desarrollo , Control de Infecciones/métodos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Cuarentena/legislación & jurisprudencia , Viaje/legislación & jurisprudencia , Betacoronavirus , COVID-19 , China , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Política de Salud , Recursos en Salud , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Medición de Riesgo , SARS-CoV-2Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Humanos , Exposición Profesional , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
BACKGROUND: Urological training has dramatically changed in recent years. Training durations are shorter and a drive toward consultant led care has reduced trainees experience. Within the UK, approximately 50 registrars annually embark on a 5-year Urology training programme, with variable levels of basic urological experience. OBJECTIVE: To describe a simulation programme aimed at delivering the knowledge and skills necessary to safely and effectively start working as a registrar in Urology by intensive training with a 1:1 faculty to delegate ratio. DESIGN, SETTING, AND PARTICIPANTS: Our course content mirrors the UK training syllabus for junior Urology registrars. We delivered 8 modules over a 4-day programme with a fifth day of assessments. Delegates level of urological knowledge, operative competency and confidence pre-, immediately post-training and at 3-months postcourse were assessed. Objective delegate and faculty feedback was also collected. Technical skills modules include; inguinoscrotal surgery, ureteroscopy, transurethral resection, urodynamics, and Botox administration as well as basic reconstructive and laparoscopic operative skills. "Nontechnical" skills included simulated ward round, out-patient, and emergency scenarios. RESULTS: Feedback from delegates and faculty members has been overwhelmingly positive. We have used this feedback to tailor the content of the course for following years. An increased knowledge level (based on mean examination scores [precourse 55.5%, postcourse 70.1%]) and operative competency was observed in all skills assessed (transurethral resection of the prostate, transurethral resection of bladder tumor, Ureteroscopy, laparoscopic skills, and instrument assembly). Operative confidence was increased immediately and at 3-months postcourse. CONCLUSIONS: Our "boot camp" course provides a realistic introduction and foundation to begin Urological practice. Being delivered at the beginning of the training scheme, prior to intensive patient exposure, registrars are in an optimum position to develop their newly acquired knowledge and skills to enhance training and intends to improve patient safety and satisfaction.
Asunto(s)
Competencia Clínica , Educación de Postgrado en Medicina/métodos , Entrenamiento Simulado , Urología/educación , Reino UnidoRESUMEN
BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the most common hospital-acquired infections, leading to increased morbidity and mortality. A major reason for this is that urinary catheters are not yet capable of preventing CAUTIs. AIM: To develop an anti-infective urinary catheter. METHODS: An efficient silver-polytetrafluoroethylene (Ag-PTFE) nanocomposite coating was deposited on whole silicone catheters, and two in-vitro bladder models were designed to test antibacterial (against Escherichia coli) and anti-encrustation (against Proteus mirabilis) performances. Each model was challenged with two different concentrations of bacterial suspension. FINDINGS: Compared with uncoated catheters, coated catheters significantly inhibited bacterial migration and biofilm formation on the external catheter surfaces. The time to develop bacteriuria was an average of 1.8 days vs 4 days and 6 days vs 41 days when the urethral meatus was infected with 106 and 102 cells/mL, respectively. For anti-encrustation tests, the coated catheter significantly resisted encrustation, although it did not strongly inhibit the increases in bacterial density and urinary pH. The time to blockage, which was found to be independent of the initial bacterial concentration in the bladder, was extended from 36.2±1.1 h (uncoated) to 89.5±3.54 h (coated) following bacterial contamination with 103 cells/mL in the bladder. Moreover, the coated catheter exhibited excellent biocompatibility with L929 fibroblast cells. CONCLUSION: Ag-PTFE coated Foley catheters should undergo further clinical trials to determine their ability to prevent CAUTIs during catheterization.
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Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanocompuestos , Politetrafluoroetileno/farmacología , Proteus mirabilis/efectos de los fármacos , Plata/farmacología , Catéteres Urinarios , Bacteriuria/prevención & control , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones por Escherichia coli/prevención & control , Humanos , Modelos Teóricos , Infecciones por Proteus/prevención & control , Factores de Tiempo , Infecciones Urinarias/prevención & controlRESUMEN
OBJECTIVE: To investigate the impact of decade-long dedicated laparoscopic urology surgical skills course on the successful implementation of surgical services by the participants. METHODS: A prospective database was maintained for all the participants in urological laparoscopic courses run by a single dedicated unit between January 2016 and December 2016. Data on various variables were collected using a follow-up validated questionnaire exploring speciality of clinical practice, challenges and need for additional training to establish clinical services, improvement in quality and frequency of laparoscopic courses. A subset of participants reported data of their outcomes in a national database available publically. RESULTS: One hundred sixty one delegates were drawn from 18 countries attended laparoscopic skills courses during the study period of 10 years. Data were available for 154 (95.65%) participants. There were only 20 (20/154; 12.9%) responses to online website questionnaires despite 3 reminders. Further, follow-up through websites/telephonic contact/organizational contacts improved the response rate to 93% (143/154). Of the participants, 95% (135/143) felt that these courses should be continued, and they agreed to recommend them to their trainees in the future. More than 50% (81/143; 56.6%) of the participants performed laparoscopic/robotic surgery at various centers. Sixty two (62/143; 43.3%) did not pursue laparoscopic surgery as a career choice. Fifty six (56/81; 69%) participants were established laparoscopic surgeons were from the UK, and of them, 30 (30/56; 53.57%: 30/81; 37.04%) were established surgeons that contributed to publishing their results through professional organizations with the outcomes of all of these within normal ranges of their peers. CONCLUSIONS: A dedicated laparoscopic urological surgery course run over a decade had a significant impact on the skills of participants, and most participants were able to establish clinical practice catering to a large proportion of the UK population as well as a few centers internationally.
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Competencia Clínica , Laparoscopía/educación , Entrenamiento Simulado , Procedimientos Quirúrgicos Urológicos/métodos , Urología/educación , Humanos , Factores de TiempoRESUMEN
BACKGROUND: Little is known about the unmet supportive care needs of patients affected by muscle invasive bladder cancer (MIBC). We set out to determine the different domains of unmet supportive care needs for patients affected by MIBC. LITERATURE SEARCH: A systematic review was conducted according to the PRISMA Statement Guidelines. A sensitive search was performed in electronic databases (DARE, Cochrane, MEDLINE, BNI, PsychINFO, EMBASE and CIHAHL) from the earliest date available to January 2017. DATA EVALUATION: 1405 references were retrieved, 8 articles met the eligibility criteria and were appraised and ranked by strength using the levels of evidence. SYNTHESIS: Individual unmet needs were classified into the following domains: patient-clinician communication, daily living needs, health system/information needs, practical needs, family-related needs, social needs, psychological needs, physical needs and intimacy needs. Patients reported high unmet needs at diagnosis and into survivorship. CONCLUSIONS: This review contributes to a greater understanding of the unmet supportive care needs of patients affected by MIBC. Findings reflect a paucity of research, but existing studies indicated needs commonly related to intimacy, informational, physical and psychological needs. Despite the emerging evidence-base, the current within study limitations precludes our understanding about how the needs of patients evolve over time.
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Músculos Abdominales/fisiopatología , Necesidades y Demandas de Servicios de Salud , Metástasis de la Neoplasia/fisiopatología , Calidad de Vida/psicología , Apoyo Social , Neoplasias de la Vejiga Urinaria/psicología , Neoplasias de la Vejiga Urinaria/secundario , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
OBJECTIVE: To determine outcomes of small renal masses (≤4 cm) on active surveillance and explore factors which can influence their growth. PATIENTS AND METHODS: Two hundred twenty six patients between January 2007 and December 2014 were analysed using cross-linked methodology of healthcare data and independent review. Cancer specific and non-specific survival were the primary outcomes. Growth kinetics, factors influencing growth and need for interventions were secondary outcomes. RESULTS: 101 (64.4%) solid and 4 (5.9%) cystic SRMs showed growth. 43 (19.02%) of SRMs required treatment interventions. Seven patients (7/158; 4.4%) died due to renal cancer at a median follow-up of 21.7 (SD 10.6, min 6-42) months, all in solid category. Independent review of serial radiological imaging of these seven cases showed two patients had subtle metastatic disease at the initial presentation, and 5 of the 7 did not adhere to recommended imaging regime. 33 (33/158; 20.8%) died due to other causes including non-renal cancers (14/158; 8.8%). Multivariate analyses showed that lower eGFR at baseline, co-morbidities and tumour location were independently associated with growth in size. CONCLUSIONS: A higher cancer-specific mortality was seen in the present study compared to the reported literature. Independent critical review of imaging of cases with poor outcome underscored the importance of adherence to a robust protocol including follow up. Comorbid conditions had a significant impact on growth and overall survival of patients with SRMs.
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Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Neoplasias Renales/terapia , Cinética , Vigilancia de la Población , Escocia , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the risk of hospitalization and death following prostate biopsy. STUDY DESIGN: Retrospective cohort study. METHODS: Our study population comprised 10,285 patients with a record of first ever prostate biopsy between 2009 and 2013 on computerized acute hospital discharge or outpatient records covering Scotland. Using the general population as a comparison group, expected numbers of admissions/deaths were derived by applying age-, sex-, deprivation category-, and calendar year-specific rates of hospital admissions/deaths to the study population. Indirectly standardized hospital admission ratios (SHRs) and mortality ratios (SMRs) were calculated by dividing the observed numbers of admissions/deaths by expected numbers. RESULTS: Compared with background rates, patients were more likely to be admitted to hospital within 30 days (SHR 2.7; 95% confidence interval 2.4, 2.9) and 120 days (SHR 4.0; 3.8, 4.1) of biopsy. Patients with prior co-morbidity had higher SHRs. The risk of death within 30 days of biopsy was not increased significantly (SMR 1.6; 0.9, 2.7), but within 120 days, the risk of death was significantly higher than expected (SMR 1.9; 1.5, 2.4). The risk of death increased with age and tended to be higher among patients with prior co-morbidity. Overall risks of hospitalization and of death up to 120 days were increased both in men diagnosed and those not diagnosed with prostate cancer. CONCLUSIONS: Higher rates of adverse events in older patients and patients with prior co-morbidity emphasizes the need for careful patient selection for prostate biopsy and justifies ongoing efforts to minimize the risk of complications.
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Biopsia/efectos adversos , Muerte , Hospitalización/estadística & datos numéricos , Próstata/patología , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Escocia/epidemiologíaRESUMEN
BACKGROUND: Little is known about the effects of socio-economic deprivation on the oncological outcomes of surgically treated upper tract transitional cell carcinoma. METHODS: From January 1998 to December 2012, 161 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical centre. We included 124 patients where complete data were available for further analysis. This study also analysed the impact of the reported risk factors such as grade, stage, multifocality in addition to socio-economic deprivation on the long-term oncological outcomes after nephroureterectomy. RESULTS: One hundred and twenty-four (77 %) patients with complete data for socio-economic status were analysed in this study. The median age of the cohort was 73 years (interquartile range 45-86). There were 20, 18, 17, 40 and 29 patients in different socio-economic categories ranging from 1 to 5, respectively. The median duration of follow-up was 68 months (9-174). A statistically higher grade (p value 0.005) and higher stage (p value 0.0005) disease was seen in patients from less deprived categories on both univariate and multivariate analyses. The cancer-specific mortality and follow-up recurrences, however, did not significantly differ between the different socio-economic categories on multivariate analysis (p value 0.13; 0.6) and on univariate and multivariate analyses. A higher number of patients with multifocal disease and concomitant carcinoma in situ (CIS) had disease recurrences which were statistically significant (p values 0.026 and 0.014, respectively) on multivariate analysis. CONCLUSIONS: A lower recurrence-free survival was observed in patients with multifocal disease and those with concomitant CIS following nephroureterectomy for clinically localized disease. Long-term follow-up did not show any significant differences in cancer-specific survival between different deprivation categories.
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Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Neoplasias Renales/cirugía , Nefrectomía , Clase Social , Neoplasias Ureterales/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/mortalidad , Estudios de Cohortes , Femenino , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/patologíaRESUMEN
BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.
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Carcinoma de Células Renales/genética , Deleción Cromosómica , Cromosomas Humanos Par 9/genética , Neoplasias Renales/genética , Recurrencia Local de Neoplasia/genética , Anciano , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/prevención & control , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Proteomics-based approaches for biomarker discovery are promising strategies used in cancer research. We present state-of-art label-free quantitative proteomics method to assess proteome of renal cell carcinoma (RCC) compared with noncancer renal tissues. METHODS: Fresh frozen tissue samples from eight primary RCC lesions and autologous adjacent normal renal tissues were obtained from surgically resected tumour-bearing kidneys. Proteins were extracted by complete solubilisation of tissues using filter-aided sample preparation (FASP) method. Trypsin digested proteins were analysed using quantitative label-free proteomics approach followed by data interpretation and pathways analysis. RESULTS: A total of 1761 proteins were identified and quantified with high confidence (MASCOT ion score threshold of 35 and P-value <0.05). Of these, 596 proteins were identified as differentially expressed between cancer and noncancer tissues. Two upregulated proteins in tumour samples (adipose differentiation-related protein and Coronin 1A) were further validated by immunohistochemistry. Pathway analysis using IPA, KOBAS 2.0, DAVID functional annotation and FLink tools showed enrichment of many cancer-related biological processes and pathways such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. CONCLUSIONS: Our study identified a number of differentially expressed proteins and pathways using label-free proteomics approach in RCC compared with normal tissue samples. Two proteins validated in this study are the focus of on-going research in a large cohort of patients.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/química , Neoplasias Renales/química , Proteómica/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/orina , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/orina , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/orina , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/orina , Transducción de SeñalRESUMEN
BACKGROUND AND OBJECTIVES: A relatively unknown associations exists between the detection, progression and rate of interventions in small renal masses in the context of socioeconomic status. The study explored the impact of socioeconomic status on the detection, progression and intervention rate in SRMs. PARTICIPANTS AND METHODS: A population-based cohort of patients with SRMs was identified using various hospital databases in well-defined geographical area between January 2007 and December 2011. A list of patients with unique 10-digits Community Health Index (CHI) number and their follow-up was recorded on a pre-designed electronic database sheet. Correlation between the socioeconomic status and detection, progression and pattern of interventions of small renal masses was the primary outcome. The postcode of each patient was identified and linked to the Scottish Index of Multiple Deprivation (SIMD) scoring system, and a deprivation category number assigned to each patient, allowing potential links to become apparent between small renal masses and deprivation. RESULTS: Two hundred and seventeen patients were diagnosed with small renal masses in 150,820 abdominal imaging carried out in a population of 117,600. The detection of SRMs in relation to SIMD status showed no statistically significant differences across different categories. Similarly, interventions, type of surgery and progression remained unaffected by socioeconomic status. The group on active surveillance showed slow or no-growth at a mean follow-up of more than 2 years. CONCLUSIONS: The detection of small renal masses is very small compared with the amount of imaging investigations of abdomen in 5 years in this cohort. Detection, progression and rate of intervention did not differ in different socioeconomic strata of the cohort. The majority of small renal masses on active surveillance did not change or grew in size very slowly when observed over time.
Asunto(s)
Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Anciano , Estudios de Cohortes , Diagnóstico por Imagen , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Neoplasias Renales/epidemiología , Masculino , Vigilancia de la Población , Factores de Riesgo , Escocia/epidemiología , Factores SocioeconómicosRESUMEN
BACKGROUND: There is growing evidence that training on virtual reality simulators leads to improved performance in the animate and human operating room. However, they are expensive, have a limited availability, and involve complex systems. Portable simulators are significantly cheaper, more user-friendly, and are flexible systems that are more suited to a surgical trainee's busy schedule. The use of portable surgical simulators to train skills and reduce errors has never been evaluated in prospective, randomized clinical settings. The objective of this study was to determine if training on the portable Integrated Laparoscopic Simulator leads to improved performance of core laparoscopic skills. METHODS: Core laparoscopic skills were identified by five experienced laparoscopic surgeons and modeled into two exercises and three basic tasks. Twenty surgically naive medical students had baseline laparoscopic skills assessed on a fixed simulator. Participants were randomized to either 14 h training on a portable laparoscopic simulator over a 3 week period, or control with no training. At 3 weeks two expert laparoscopic surgeons blinded to the allocation of participants assessed their pre- and post-intervention performances recorded on a CD-ROM. The outcome measures included time to complete and global rating scores of clipping and dissection tasks. RESULTS: No differences were observed in baseline skills level between the two groups. The intervention group had better quality of scissors dissection (p = 0.0038) and improved clipping skills (p = 0.0051), and they took less time to accomplish the tasks (p = 0.0099) in comparison to control. CONCLUSIONS: Training on the portable Integrated Laparoscopic Simulator significantly improved core laparoscopic skills in medical students with no prior experience.