Bowenle1209
A liquid biopsy may help identify patients with operable urothelial cancer who stand to benefit from adjuvant immunotherapy. In the IMvigor010 study, patients who tested positive for circulating tumor DNA showed improvement in disease-free survival and overall survival if they received adjuvant atezolizumab instead of observation.Natural killer (NK) cells and T cells are key effectors of anti-tumor immune responses and major targets of checkpoint inhibitors. In multiple cancer types, we find that the expression of Wnt signaling potentiator R-spondin genes (e.g. RSPO3) is associated with favorable prognosis and is positively correlated with gene signatures of both NK cells and T cells. While endothelial cells and cancer-associated fibroblasts comprise the R-spondin3-producing cells, NK cells and T cells correspondingly express the R-spondin3 receptor LRG6 within the tumor microenvironment. Exogenous expression or intratumor injection of R-spondin3 in tumors enhanced the infiltration and function of cytotoxic effector cells, which led to tumor regression. NK cells and CD8+ T cells independently and cooperatively contributed to R-spondin3-induced control of distinct tumor types. The effect of R-spondin3 was mediated in part through upregulation of MYC and ribosomal biogenesis. Importantly, R-spondin3 expression enhanced tumor sensitivity to anti-PD1 therapy, thereby highlighting new therapeutic avenues.
The rapid ageing population of Hong Kong has a high demand on oncology and palliative care (PC) service. This study was the first territory-wide assessment in Hong Kong to assess the palliative service coverage in patients with advanced cancer in the past decade.
Cancer deaths of all 43 public hospitals of Hong Kong were screened. Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at 4 time points (2006, 2009, 2012, 2015). Individual patient records were thoroughly reviewed. Predictors of PC coverage was evaluated in univariable and multivariable analyses.
From 2006 to 2015, PC coverage improved steadily from 55.4% to 68.9% (p<0.001). Median time of referral to PC service to death was 25 days (IQR 53). For duration of inpatient PC, the median time was 22 days (IQR 44) and it was stable over the past 10 years. Median time of referral to outpatient service to death was 74 days (IQR 144) and there was an improvement observed (p<0.05). The current system was highly heterogeneous that PC varied between 9.8% and 84.8% in different hospitals depending on the PC service infrastructure. Multivariable Cox model identified patients associated with lower PC coverage male, <50, rapid disease deterioration and staying in hospitals without multidisciplinary team clinic and designated palliative bed support (all p<0.01).
There was concrete achievement in palliative service development in the past decade. Heterogeneity and late service provision should be addressed in future.
There was concrete achievement in palliative service development in the past decade. Heterogeneity and late service provision should be addressed in future.
To evaluate the feasibility and efficacy of a serious illness decision aid (Plan Well Guide) in increasing the engagement of substitute decision-makers (SDM) in advance care planning (ACP).
This trial was conducted (2017-2019) in outpatient settings in Ontario, Canada, aiming to recruit 90 dyads of patients aged 65 years and older at high risk of needing future medical decisions and their SDM. Participants were randomised to receive the intervention immediately or to a 3-month wait period. The Plan Well Guide was administered to the patient and SDM by a facilitator. Outcomes were change on the validated 17-item SDM ACP Engagement Survey (primary) and 15-item patient ACP Engagement Survey (secondary).
Of 136 dyads approached, 58 consented and were randomised and 45 completed the study (28 immediate intervention, 17 delayed intervention). The trial was stopped early because of difficulties with enrolling and following up participants. The mean changes on the SDM ACP Engagement Survey and the patient ACP Engagement Survey favoured the first group but were not statistically significant (mean difference (MD)=+0.2 (95% CI -0.3 to 0.6) and MD=+0.4 (95% CI -0.1 to 0.8), respectively). In a post-hoc subgroup analysis, significant treatment effects were seen in SDMs with a lower-than-median baseline score compared with those at or above the median.
In this statistically underpowered randomised trial, differences in SDM ACP engagement between groups were small. Further information is needed to overcome recruitment challenges and to identify people most likely to benefit from the Plan Well Guide.Trial registration number NCT03239639.
In this statistically underpowered randomised trial, differences in SDM ACP engagement between groups were small. Further information is needed to overcome recruitment challenges and to identify people most likely to benefit from the Plan Well Guide.Trial registration number NCT03239639.
Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD.
The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO
), particulate matter (PM
), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments.
Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products.
NCT04107701.
NCT04107701.Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P less then 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.Electronic skins (e-skins)-electronic sensors mechanically compliant to human skin-have long been developed as an ideal electronic platform for noninvasive human health monitoring. For reliable physical health monitoring, the interface between the e-skin and human skin must be conformal and intact consistently. However, conventional e-skins cannot perfectly permeate sweat in normal day-to-day activities, resulting in degradation of the intimate interface over time and impeding stable physical sensing. Here, we present a sweat pore-inspired perforated e-skin that can effectively suppress sweat accumulation and allow inorganic sensors to obtain physical health information without malfunctioning. The auxetic dumbbell through-hole patterns in perforated e-skins lead to synergistic effects on physical properties including mechanical reliability, conformability, areal mass density, and adhesion to the skin. The perforated e-skin allows one to laminate onto the skin with consistent homeostasis, enabling multiple inorganic sensors on the skin to reliably monitor the wearer's health over a period of weeks.Charge order is universal to all hole-doped cuprates. Yet, the driving interactions remain an unsolved problem. Electron-electron interaction is widely believed to be essential, whereas the role of electron-phonon interaction is unclear. We report an ultrahigh-resolution resonant inelastic x-ray scattering (RIXS) study of the in-plane bond-stretching phonon mode in stripe-ordered cuprate La1.675Eu0.2Sr0.125CuO4 Phonon softening and lifetime shortening are found around the charge ordering wave vector. In addition to these self-energy effects, the electron-phonon coupling is probed by its proportionality to the RIXS cross section. We find an enhancement of the electron-phonon coupling around the charge-stripe ordering wave vector upon cooling into the low-temperature tetragonal structure phase. These results suggest that, in addition to electronic correlations, electron-phonon coupling contributes substantially to the emergence of long-range charge-stripe order in cuprates.Chirality plays a key role in the physiological system, because molecular functionalities may drastically alter due to a change in chirality. We report herein a unique color indicator with a static helicity memory, which exhibits visible color changes in response to the chirality of chiral amines. A difference of less than 2% in the enantiomeric excess (ee) values causes a change in the absorption that is visible to the naked eyes. This was further quantified by digital photography by converting to RGB values. selleck This system relies on the change in the tunable helical pitch of the π-conjugated polymer backbone in specific solvents and allows rapid on-site monitoring of chirality of nonracemic amines, including drugs, and the simultaneous quantitative determination of their ee values.
