AIMTo assess the development and implementation of the Integrated Rapid Assessment and Treatment(IRAT)pathway for the management of patients with fecal incontinence and measure its impact on patients’care.METHODSPati...AIMTo assess the development and implementation of the Integrated Rapid Assessment and Treatment(IRAT)pathway for the management of patients with fecal incontinence and measure its impact on patients’care.METHODSPatients referred to the colorectal unit in our hospital for the management of faecal incontinence were randomised to either the Standard Care pathway or the newly developed IRAT pathway in this feasibility study.The IRAT pathway is designed to provide a seamless multidisciplinary care to patients with faecal incontinence in a timely fashion.On the other hand,patients in the Standard Pathway were managed in the general colorectal clinic.Percentage improvements in St.Marks Incontinence Score,Cleveland Clinic Incontinence Score and Rockwood Faecal Incontinence Quality of Life Scale after completion of treatment in both groups were the primary outcome measures.Secondary endpoints were the time required to complete the management and patients’satisfaction score.χ<sup>2</sup>,Mann-Whitney-U and Kendall tau-c correlation coefficient tests were used for comparison of outcomes of the two study groups.A P value of 0.05 or less was considered significant.RESULTSThirty-nine patients,34 females,consented to participate.Thirty-one(79.5%)patients completed the final assessment and were included in the outcome analysis.There was no significant difference in the quality of life scales and incontinence scores.Patients in the IRAT pathway were more satisfied with the time required to complete management(P=0.033)and had stronger agreement that all aspects of their problem were covered(P=0.006).CONCLUSIONDespite of the lack of significant difference in outcome measures,the new pathway has positively influenced patient’s mindset,which was reflected in a higher satisfaction score.展开更多
Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include p...Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include programmed death-1(PD-1), cytotoxic T lymphocyte associated antigen-4(CTLA-4), lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, Glucocorticoid-induced TNFR family-related receptor(GITR), and killer cell immunoglobulin like receptor. With the exception of GITR, after binding to their respective ligands these checkpoints induce down-modulation of immune responses to prevent autoimmunity. However, such immune mechanisms are co-opted by tumors to allow rapid tumor cell proliferation. Pre-clinical studies in antibody blockade of PD-1 and CTLA-4 have led to promising augmentation of effector immune responses in murine tumor models, and human antibodies against PD-1 and CTLA-4 alone or in combination have demonstrated tumor regression in clinical trials. The development of immune checkpoint blockade as a potential future immunotherapy has led to increasing interest in combining treatment modalities. Combination checkpoint blockade with chemotherapy and radiation therapy has shown synergistic effects in pre-clinical and clinical studies, and combination checkpoint blockade with bacterial vaccine vectors have produced increased effector immune responses in pre-clinical models. The future of immune checkpoint blockade may be as a powerful adjuvant alongside the current standard of care.展开更多
Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemothe...Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemotherapy and radiation. Cancer immunotherapy has made great strides since the advent of anti-PD-1, anti-CTLA-4, and other immune checkpoint inhibitors. With the advancement of novel therapeutics, more clinical trials for patients have opened as well. An important future direction of clinical trials is the ability to identify appropriate patients to optimize treatment response and minimize toxicities. This review describes considerations in designing future GBM clinical trials in not only immunotherapy but also with other promising treatments. We will discuss factors, such as pseudoprogression, genetic and circulating biomarkers, and the commensal microbiome of patients in the setting of clinical trial design.展开更多
Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia a...Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and macrophages, despite a growing body of evidence that demonstrates key structural and functional differences between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future directions for new treatment modalities.展开更多
文摘AIMTo assess the development and implementation of the Integrated Rapid Assessment and Treatment(IRAT)pathway for the management of patients with fecal incontinence and measure its impact on patients’care.METHODSPatients referred to the colorectal unit in our hospital for the management of faecal incontinence were randomised to either the Standard Care pathway or the newly developed IRAT pathway in this feasibility study.The IRAT pathway is designed to provide a seamless multidisciplinary care to patients with faecal incontinence in a timely fashion.On the other hand,patients in the Standard Pathway were managed in the general colorectal clinic.Percentage improvements in St.Marks Incontinence Score,Cleveland Clinic Incontinence Score and Rockwood Faecal Incontinence Quality of Life Scale after completion of treatment in both groups were the primary outcome measures.Secondary endpoints were the time required to complete the management and patients’satisfaction score.χ<sup>2</sup>,Mann-Whitney-U and Kendall tau-c correlation coefficient tests were used for comparison of outcomes of the two study groups.A P value of 0.05 or less was considered significant.RESULTSThirty-nine patients,34 females,consented to participate.Thirty-one(79.5%)patients completed the final assessment and were included in the outcome analysis.There was no significant difference in the quality of life scales and incontinence scores.Patients in the IRAT pathway were more satisfied with the time required to complete management(P=0.033)and had stronger agreement that all aspects of their problem were covered(P=0.006).CONCLUSIONDespite of the lack of significant difference in outcome measures,the new pathway has positively influenced patient’s mindset,which was reflected in a higher satisfaction score.
文摘Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include programmed death-1(PD-1), cytotoxic T lymphocyte associated antigen-4(CTLA-4), lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, Glucocorticoid-induced TNFR family-related receptor(GITR), and killer cell immunoglobulin like receptor. With the exception of GITR, after binding to their respective ligands these checkpoints induce down-modulation of immune responses to prevent autoimmunity. However, such immune mechanisms are co-opted by tumors to allow rapid tumor cell proliferation. Pre-clinical studies in antibody blockade of PD-1 and CTLA-4 have led to promising augmentation of effector immune responses in murine tumor models, and human antibodies against PD-1 and CTLA-4 alone or in combination have demonstrated tumor regression in clinical trials. The development of immune checkpoint blockade as a potential future immunotherapy has led to increasing interest in combining treatment modalities. Combination checkpoint blockade with chemotherapy and radiation therapy has shown synergistic effects in pre-clinical and clinical studies, and combination checkpoint blockade with bacterial vaccine vectors have produced increased effector immune responses in pre-clinical models. The future of immune checkpoint blockade may be as a powerful adjuvant alongside the current standard of care.
文摘Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemotherapy and radiation. Cancer immunotherapy has made great strides since the advent of anti-PD-1, anti-CTLA-4, and other immune checkpoint inhibitors. With the advancement of novel therapeutics, more clinical trials for patients have opened as well. An important future direction of clinical trials is the ability to identify appropriate patients to optimize treatment response and minimize toxicities. This review describes considerations in designing future GBM clinical trials in not only immunotherapy but also with other promising treatments. We will discuss factors, such as pseudoprogression, genetic and circulating biomarkers, and the commensal microbiome of patients in the setting of clinical trial design.
文摘Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and macrophages, despite a growing body of evidence that demonstrates key structural and functional differences between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future directions for new treatment modalities.
