Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials

To estimate the magnitude of benefit of chemotherapy in prolonging survival for patients with metastatic colorectal cancer, a meta-analysis of randomized controlled trial was performed. A systematic search was performed to identify randomized trials comparing chemotherapy with observation or supportive care alone. Trials were assessed for quality of reporting, publication bias and heterogeneity. Relative risks for outcomes from published data were pooled using a random-effects model. Seven trials with 614 patients were included. All trials used fluoropyrimidine-based chemotherapy, through a variety of routes and schedules, including intravenous, intra-portal and hepatic arterial infusion. Compared with the ‘no-chemotherapy’ arm, chemotherapy significantly reduced 1-year mortality (risk ratio 0.69; 95% confidence interval (CI) 0.60–0.81, P< 0.00001). The mortality at 2 years was not significantly different (risk ratio 0.93; 95% CI 0.87–1.00, P = 0.053). Between-trial comparisons demonstrated benefit with a variety of routes and schedules. Chemotherapy significantly prolongs 1-year survival for patients with metastatic colorectal cancer, and should be offered to those with good performance status. © 2000 Cancer Research Campaig

Is Extended Volume of External Beam Irradiation Beneficial in Post-esophagectomy High Risk Patients Receiving Combined Chemoradiation Therapy?

OBJECTIVE: To assess the value of extended volume irradiation with anastomotic coverage in high risk resected esophageal cancer patients. METHOD: A retrospective study was undertaken at LRCC from 1989-1999 for high risk resected esophageal cancer patients. Adjuvant treatments consisted of 4 cycles of chemotherapy (epirubicin/fluorouracil/cisplatin or cisplatin/fluorouracil), and local regional irradiation with or without coverage of the anastomotic site. Radiation dose ranged from 45-60Gy at 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage) or small (without anastomotic coverage) field followed by oblique fields for boost. RESULT: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation therapy. Three patients had disease progression prior to therapy, and 69 patients were analyzed. There were 81% T3N1 and 13% T2N1. Thirty-four patients had margin involvements (radial 53%; proximal/distal 32%), 65% were adenocarcinoma and 33% were squamous carcinoma. Median followup was 23.6 months (3.4 - 78.4 months). Two year survival was 50%; 5yr 24%. Relapse rate was 62.3% and median time to relapse was 20 months. Recurrence locally to anastomosis or adjacent to anastomosis was 9/43(20.9%) with small field and 2/26(7.7%) with extended field. Of 31 patients with relapse outside anastomosis, 14/20(70%) relapsed locoregional/distal when treated with small field and 3/11(27%) relapsed locoregional/distal when treated with extended field (p=0.02). There was no excess treatment interruption or chronic gastrointestinal toxicity with extended field irradiation. CONCLUSION: There is significant decrease in locoregional/distal relapse with use of extended field in high risk resected esophageal cancer patients

Exposure to moral stressors and associated outcomes in healthcare workers:Prevalence, correlates, and impact on job attrition

Introduction: Healthcare workers (HCWs) often experience morally challenging situations in their workplaces that may contribute to job turnover and compromised well-being. This study aimed to characterize the nature and frequency of moral stressors experienced by HCWs during the COVID-19 pandemic, examine their influence on psychosocial-spiritual factors, and capture the impact of such factors and related moral stressors on HCWs’ self-reported job attrition intentions.Methods: A sample of 1204 Canadian HCWs were included in the analysis through a web-based survey platform whereby work-related factors (e.g. years spent working as HCW, providing care to COVID-19 patients), moral distress (captured by MMD-HP), moral injury (captured by MIOS), mental health symptomatology, and job turnover due to moral distress were assessed.Results: Moral stressors with the highest reported frequency and distress ratings included patient care requirements that exceeded the capacity HCWs felt safe/comfortable managing, reported lack of resource availability, and belief that administration was not addressing issues that compromised patient care. Participants who considered leaving their jobs (44%; N = 517) demonstrated greater moral distress and injury scores. Logistic regression highlighted burnout (AOR = 1.59; p &lt; .001), moral distress (AOR = 1.83; p &lt; .001), and moral injury due to trust violation (AOR = 1.30; p = .022) as significant predictors of the intention to leave one’s job.Conclusion: While it is impossible to fully eliminate moral stressors from healthcare, especially during exceptional and critical scenarios like a global pandemic, it is crucial to recognize the detrimental impacts on HCWs. This underscores the urgent need for additional research to identify protective factors that can mitigate the impact of these stressors.Introducción: Los trabajadores de la salud (TS) a menudo experimentan situaciones moralmente desafiantes en sus lugares de trabajo que pueden contribuir a la rotación laboral y comprometer su bienestar. Este estudio tuvo como objetivo caracterizar la naturaleza y frecuencia de los estresores morales experimentados por los TS durante la pandemia por COVID-19, examinar su influencia en los factores psicosociales-espirituales y capturar el impacto de dichos factores y los estresores morales relacionados a las intenciones de abandono laboral de los TS.Métodos: Se incluyó en el análisis una muestra de 1.204 TS canadienses a través de una encuesta en plataforma web en la que se analizaron factores relacionados con el trabajo (p. ej., años trabajados como TS, brindando atención a pacientes con COVID-19), angustia moral (evaluado con MMD-HP), daño moral (evaluado con MIOS), sintomatología de salud mental y rotación laboral debido a angustia moral.Resultados: Los estresores morales con mayor frecuencia reportados y tasas de angustia incluyeron requerimientos de atención al paciente que excedieron la capacidad en la que los TS se sentían seguros/cómodos de manejarlos, falta de disponibilidad de recursos y la creencia de que la administración no estaba abordando los problemas que comprometían la atención al paciente. Los participantes que consideraron dejar sus trabajos (44%; N = 517) demostraron mayores puntuaciones de angustia y daño moral. La regresión logística destacó el burnout (AOR = 1,59; p &lt; 0,001), la angustia moral (AOR = 1,83; p &lt; 0,001) y el daño moral debido a la violación de la confianza (AOR = 1,30; p = 0,022) como predictores significativos asociados a la intención de dejar el trabajo.Conclusión: Si bien, es imposible eliminar por completo los estresores morales de la atención sanitaria, especialmente durante escenarios críticos y excepcionales como una pandemia global, es crucial reconocer los impactos perjudiciales para los TS. Esto subraya la necesidad urgente de realizar investigaciones adicionales para identificar factores protectores que puedan mitigar el impacto de estos factores estresantes.</div

Exposure to moral stressors and associated outcomes in healthcare workers:Prevalence, correlates, and impact on job attrition

Introduction: Healthcare workers (HCWs) often experience morally challenging situations in their workplaces that may contribute to job turnover and compromised well-being. This study aimed to characterize the nature and frequency of moral stressors experienced by HCWs during the COVID-19 pandemic, examine their influence on psychosocial-spiritual factors, and capture the impact of such factors and related moral stressors on HCWs’ self-reported job attrition intentions.Methods: A sample of 1204 Canadian HCWs were included in the analysis through a web-based survey platform whereby work-related factors (e.g. years spent working as HCW, providing care to COVID-19 patients), moral distress (captured by MMD-HP), moral injury (captured by MIOS), mental health symptomatology, and job turnover due to moral distress were assessed.Results: Moral stressors with the highest reported frequency and distress ratings included patient care requirements that exceeded the capacity HCWs felt safe/comfortable managing, reported lack of resource availability, and belief that administration was not addressing issues that compromised patient care. Participants who considered leaving their jobs (44%; N = 517) demonstrated greater moral distress and injury scores. Logistic regression highlighted burnout (AOR = 1.59; p &lt; .001), moral distress (AOR = 1.83; p &lt; .001), and moral injury due to trust violation (AOR = 1.30; p = .022) as significant predictors of the intention to leave one’s job.Conclusion: While it is impossible to fully eliminate moral stressors from healthcare, especially during exceptional and critical scenarios like a global pandemic, it is crucial to recognize the detrimental impacts on HCWs. This underscores the urgent need for additional research to identify protective factors that can mitigate the impact of these stressors.Introducción: Los trabajadores de la salud (TS) a menudo experimentan situaciones moralmente desafiantes en sus lugares de trabajo que pueden contribuir a la rotación laboral y comprometer su bienestar. Este estudio tuvo como objetivo caracterizar la naturaleza y frecuencia de los estresores morales experimentados por los TS durante la pandemia por COVID-19, examinar su influencia en los factores psicosociales-espirituales y capturar el impacto de dichos factores y los estresores morales relacionados a las intenciones de abandono laboral de los TS.Métodos: Se incluyó en el análisis una muestra de 1.204 TS canadienses a través de una encuesta en plataforma web en la que se analizaron factores relacionados con el trabajo (p. ej., años trabajados como TS, brindando atención a pacientes con COVID-19), angustia moral (evaluado con MMD-HP), daño moral (evaluado con MIOS), sintomatología de salud mental y rotación laboral debido a angustia moral.Resultados: Los estresores morales con mayor frecuencia reportados y tasas de angustia incluyeron requerimientos de atención al paciente que excedieron la capacidad en la que los TS se sentían seguros/cómodos de manejarlos, falta de disponibilidad de recursos y la creencia de que la administración no estaba abordando los problemas que comprometían la atención al paciente. Los participantes que consideraron dejar sus trabajos (44%; N = 517) demostraron mayores puntuaciones de angustia y daño moral. La regresión logística destacó el burnout (AOR = 1,59; p &lt; 0,001), la angustia moral (AOR = 1,83; p &lt; 0,001) y el daño moral debido a la violación de la confianza (AOR = 1,30; p = 0,022) como predictores significativos asociados a la intención de dejar el trabajo.Conclusión: Si bien, es imposible eliminar por completo los estresores morales de la atención sanitaria, especialmente durante escenarios críticos y excepcionales como una pandemia global, es crucial reconocer los impactos perjudiciales para los TS. Esto subraya la necesidad urgente de realizar investigaciones adicionales para identificar factores protectores que puedan mitigar el impacto de estos factores estresantes.</div

Quantum optical time-of-arrival model in three dimensions

We investigate the three-dimensional formulation of a recently proposed operational arrival-time model. It is shown that within typical conditions for optical transitions the results of the simple one-dimensional version are generally valid. Differences that may occur are consequences of Doppler and momentum-transfer effects. Ways to minimize these are discussed.Comment: 14 pages, 5 figure

A rare combination of an endocrine tumour of the common bile duct and a follicular lymphoma of the ampulla of Vater: a case report and review of the literature

Carcinoid tumours of the common bile duct represent an extremely rare entity. Similarly, primary follicular lymphomas of the ampulla of Vater constitute an infrequent neoplasia. Herein, we report the first case of a synchronous development of a carcinoid tumour of the common bile duct and an ampullary follicular lymphoma that was treated surgically with a Whipple's procedure, due to inability to establish definitive preoperative diagnosis despite the extensive diagnostic investigation

Firefly Luciferase and Rluc8 Exhibit Differential Sensitivity to Oxidative Stress in Apoptotic Cells

Over the past decade, firefly Luciferase (fLuc) has been used in a wide range of biological assays, providing insight into gene regulation, protein-protein interactions, cell proliferation, and cell migration. However, it has also been well established that fLuc activity can be highly sensitive to its surrounding environment. In this study, we found that when various cancer cell lines (HeLa, MCF-7, and 293T) stably expressing fLuc were treated with staurosporine (STS), there was a rapid loss in bioluminescence. In contrast, a stable variant of Renilla luciferase (RLuc), RLuc8, exhibited significantly prolonged functionality under the same conditions. To identify the specific underlying mechanism(s) responsible for the disparate sensitivity of RLuc8 and fLuc to cellular stress, we conducted a series of inhibition studies that targeted known intracellular protein degradation/modification pathways associated with cell death. Interestingly, these studies suggested that reactive oxygen species, particularly hydrogen peroxide (H2O2), was responsible for the diminution of fLuc activity. Consistent with these findings, the direct application of H2O2 to HeLa cells also led to a reduction in fLuc bioluminescence, while H2O2 scavengers stabilized fLuc activity. Comparatively, RLuc8 was far less sensitive to ROS. These observations suggest that fLuc activity can be substantially altered in studies where ROS levels become elevated and can potentially lead to ambiguous or misleading findings