Corneliussenpovlsen7337
Gonda and colleagues provide preclinical proof of concept for a new therapeutic strategy and address an unmet need for this difficult to treat disease.See related article by Gonda et al., p. 4754.
Identification of people with deteriorating health is essential for quality patient-centred care and optimal management. The Supportive and Palliative Care Indicators Tool (SPICT) is a guide to identifying people with deteriorating health for care planning without incorporating a prognostic time frame.
To improve renal nursing staff confidence in identifying patients approaching end-of-life and advocate for appropriate multidisciplinary care planning.
This pilot feasibility prospective cohort study conducted in the renal ward of a major metropolitan health service during 2019 included a preintervention/postintervention survey questionnaire. A programme of education was implemented training staff to recognise end-of-life and facilitate appropriate care planning.
Several domains in the postintervention survey demonstrated a statistically significant improvement in renal nurses' perception of confidence in their ability to recognise end of life. Of the 210 patients admitted during the study period, 16% we with goals of care documented.The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L-NTRK fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods.SARS-CoV-2-infected inpatients who are admitted to a noncritical care medical ward require a standardized approach that is based on evidence if available, and effective supportive and respiratory care. Outcomes are better when patients receive standardized care, in special COVID-19 wards in the hospital, from clinical teams with expertise. Available evidence and guidelines should be continuously appraised and integrated into clinical protocols for all domains of treatment, including isolation, and personal protective measures, pharmacologic therapy, and transitions of care. Inpatient pharmacologic therapy at this time consists primarily of dexamethasone and remdesivir, along with thromboprophylaxis, given the coagulopathy associated with COVID-19. This article summarizes current practices in our organization.Racial disparities in colorectal cancer incidence are widely documented. There are two potential mechanisms for these disparities differences in access to screening, including screening follow-up, and differences in underlying risk of colorectal cancer. We reviewed the literature for evidence of these two mechanisms. We show that higher colorectal cancer incidence in blacks relative to whites emerged only after the dissemination of screening and describe evidence of racial disparities in screening rates. In contrast to the strong evidence for differences in colorectal cancer screening utilization, there is limited evidence for racial differences in adenoma prevalence. In general, black and white patients who are screened have similar adenoma prevalence, though there is some evidence that advanced adenomas and adenomas in the proximal colon are somewhat more likely in black than white patients. We conclude that higher rates of colorectal cancer incidence among black patients are primarily driven by lower rates of colorectal cancer screening. Our findings highlight the need to increase black patients' access to quality screening to reduce colorectal cancer incidence and mortality.
Prior studies evaluating diet quality in relation to ovarian cancer survival are sparse, and to date none have assessed diet quality or diet-quality change after diagnosis.
In the prospective Ovarian cancer Prognosis And Lifestyle (OPAL) study, diet-quality scores were calculated using data from food frequency questionnaires completed pre-diagnosis (
= 650) and 12 months' post-diagnosis (
= 503). We used Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between diet quality and survival.
During the median follow-up of 4.4 years, 278 women died from ovarian cancer. There was no evidence of an association between diet quality pre- or post-diagnosis and progression-free, overall, or ovarian cancer-specific survival. No survival advantage was observed for women who had either improved their diet quality or who consumed a high-quality diet both before and 12 months after diagnosis.
Higher pre- and post-diagnosis diet quality was not associated with better survival outcomes in this cohort of women with ovarian cancer.
Diet quality is important for a range of health outcomes but may not improve survival after a diagnosis of ovarian cancer.
Diet quality is important for a range of health outcomes but may not improve survival after a diagnosis of ovarian cancer.
Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.
Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.
Genetic correlation analysis revealed significant genetic correlation between the two cancers (
= 0.43,
= 2.66 × 10
). We found seven loci associated with risk for both cancers (
< 2.4 × 10
). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (
< 5 × 10
). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.
Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.
Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk.
This registry-based, nested case-control study, 110 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose-response trends.
We found 145 associations among 1,230 drug-cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug-cancer combinations are presented in this article and an online tool (https//pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk.
This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies.
DWAS studies are robust and important tools to define new drug-cancer hypotheses.
.
DWAS studies are robust and important tools to define new drug-cancer hypotheses.See related commentary by Wang and Gadalla, p. 597.
Exposure to higher levels of melatonin may be associated with lower breast cancer risk, but epidemiologic evidence has been limited. We examined the relationship in a case-control study nested within the Diagnostisch Onderzoek Mammacarcinoom (DOM) study and conducted a meta-analysis of prospective studies.
Concentrations of 6-sulfatoxymelatonin (aMT6s) in prediagnostic first morning urine voids were measured in 274 postmenopausal women diagnosed with breast cancer and 274 matched controls from the DOM study. Conditional logistic regression models were used to estimate multivariable adjusted ORs of breast cancer for thirds of aMT6s. Meta-analysis of this and previous prospective studies of urinary melatonin with breast cancer risk estimated the inverse-variance weighted averages of study-specific log RRs of breast cancer for the highest versus lowest levels of aMT6s.
In the DOM study, the ORs of breast cancer for the middle and highest versus lowest thirds of aMT6s were 0.70 [95% confidence interval (CI), 0.45-1.09] and 0.72 (95% CI, 0.44-1.19), respectively. In the meta-analysis of the DOM study with six previous studies (2,296 cases), RR of breast cancer for the highest versus lowest levels of aMT6s was 0.87 (95% CI, 0.76-1.01).
Results from the DOM study, together with the published prospective data, do not support a strong association of melatonin with breast cancer risk.
This study adds to the relatively scarce prospective data on melatonin in relation to breast cancer risk. The totality of the prospective evidence does not clearly show an association between melatonin and breast cancer risk, but further data are needed to be able to exclude a modest association.
This study adds to the relatively scarce prospective data on melatonin in relation to breast cancer risk. The totality of the prospective evidence does not clearly show an association between melatonin and breast cancer risk, but further data are needed to be able to exclude a modest association.
