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Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
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ABSTRACTCommunication between health professionals and patients is an intergroup phenomenon where the health professional has the most power and status. Over the past few decades, there has been a steady increase in the availability to patients of information about healthcare and specific diseases on the Internet. In this paper, we ask whether the use of Internet health information assists patients to manage their consultations with health professionals better and whether it alters the intergroup dynamic by providing a more equal status for patients. In this study 370 participants from Australia and Canada completed a survey that included a ‘willingness to communicate with health professionals’ scale. They also commented on their use and trust of Internet health information. Thematic analysis suggests that patients’ use of Internet health information serves as a broker between patients and their health provider in health consultations. We discuss the implications of these findings for health practitioners as they address how easier Internet access influences patient interactions with health professionals. We consider future research directions these finding provide in explaining communication behaviour in this context. 相似文献
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Camille Veit 《Annales médico-psychologiques》2019,177(4):347-351
Objectives
This paper introduces some epistemology about mental health developments and how it leads to reconsider the landscape of clinical practices.Materials
From an epistemological point of view, the author reviews several writings about mental hygiene going back to the nineteenth century. It clarifies the common roots between mental hygiene and mental health. Then, the article examines the first World Health Organization's reports, that shed light on psychiatric and political issues in the middle of the twentieth century, which allows to reach out the foundations of mental health as a discursive practice.Results
The review of the developments from “mental hygiene” to “mental health” highlights a general climate of redesign on many points: Mental health as a discursive space is characterized by an expansion of its address field. It is not only addressed to specialists, psychiatrist and psychiatric patients, but also, and above all, to every citizen. Psychic suffering, as far as mental illness, is part of a larger whole including what preserves or deteriorates the proper functioning of an individual, within society. Mental health is at the crossroads of financial, political, citizen's rights and social interests. Contemporary mental health relies on the objectives of prevention and promotion. Clinical practices are organized by some discourses with mental health as a key word. At the turn of 2000s, French psychiatry has been impacted by many shuffles in health policies. However, the roots of these restructuring are not new, as they update an old interest in safeguarding public health, funds and welfare. Psychic suffering and mental illness recently enter the field of “psychic disability”. It brought social benefits such as financial assistance from the state. It may also contribute to the campaigns of awareness-raising and destigmatization among the public opinion. However, financial and subjective effects do not perfectly match. In other words, the benefits listed above should not lead to desert the listening of the users’ experience in its singularity.Conclusions
The developments of mental health point out a reorganization in the psychiatric field and open new clinical challenges. If the spaces of singularity and universal are in a permanent relationship, the political and economic sides cannot answer or evacuate the subjectivity posed by the subject and his suffering. It should lead to focus on a clinical practice driven by a subtle listening, which does not exclude psychopathology and recognizes the importance of alterity. 相似文献6.
R. Watson T. Kozlowski V. Nickeleit J. T. Woosley J. L. Schmitz S. L. Zacks J. H. Fair D. A. Gerber K. A. Andreoni 《American journal of transplantation》2006,6(12):3022-3029
Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d. 相似文献
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In 1981 a statewide program supplying free insulin to 3,720 patients of state health clinics was discontinued. We attempted to assess whether this action had an adverse effect medically and financially on those concerned. A computer randomized sample of 351 patients (9%) was studied by personal interview and questionnaire. Information obtained focused on certain events that occurred 18 months before and after the program ceased. Measurements used to determine medical impact were number of hospitalizations, emergency room and physician visits, changes in weight and glucose levels, and episodes of ketoacidosis. Financial impact was measured by cost of hospitalization and physician visits. Our results revealed no significant changes in any of the medical parameters studied except for fasting serum glucose levels above 300 mg/dl, which occurred less frequently after the free insulin program was discontinued. There were fewer hospitalizations, more visits to physicians, and no change in number of emergency room visits after discontinuance of the free program. The overall cost saving was estimated to be +883,558 for the 18-month study period, in addition to the +550,000 the plan had been costing the state. 相似文献
10.
Tauseef Ahmed Alan Yagoda Howard I. Scher Cora Sternberg Robin C. Watson 《Investigational new drugs》1986,4(2):171-174
Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m2 IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m2 depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers. 相似文献