Abernathyrandrup8402
Black, white, and Asian/Pacific Islander patients with early-onset colorectal cancer have different patterns of nonsilent mutations than those diagnosed at a later age, researchers reported during the first week of the virtual American Association for Cancer Research Annual Meeting 2021. In addition, among those with early-onset cancer, Black patients had a significantly higher tumor mutation burden than white patients.Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers (GC) and associated with clinical response to anti-programmed death (PD)-1 antibodies. However, 50% of microsatellite instability-high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in advanced MSI-H GC patients and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. The number of whole-exome sequencing (WES)-derived nonsynonymous mutations correlated with anti-tumor activity and prolonged progression-free survival (PFS). Coupling WES to single-cell RNA sequencing, we identified dynamic tumor evolution with greater on treatment collapse of mutational architecture in responders. Diverse T-cell receptor repertoire was associated with longer PFS to pembrolizumab. Additionally, increase in PD-1+ CD8+ T cells correlated with durable clinical benefit. mTOR inhibitor Our findings highlight the genomic, immunologic, and clinical outcome heterogeneity within MSI-H GC and may inform development of strategies to enhance responsiveness.In 2020, the COVID-19 pandemic led to an unprecedented destabilization of the world's health and economic systems. The rapid spread and life-threatening consequences of COVID-19 have imposed testing of repurposed drugs, by investigating interventions already used in other indications, including anticancer drugs. The contours of anticancer drug repurposing have been shaped by similarities between the pathogenesis of COVID-19 and malignancies, including abnormal inflammatory and immunologic responses. In this review, we discuss the salient positive and negative points of repurposing anticancer drugs to advance treatments for COVID-19. SIGNIFICANCE Targeting anti-inflammatory pathways with JAK/STAT inhibitors or anticytokine therapies aiming to curb COVID-19-related cytokine storm, using antiangiogenic drugs to reduce vascular abnormalities or immune-checkpoint inhibitors to improve antiviral defenses, could be of value in COVID-19. However, conflicting data on drug efficacy point to the need for better patient selection and biomarker studies.
Brolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.
Patients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).
Sixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was 0.03±0.14 logMAR (p=0.115). Significant reductions were recorded for FCP with a mean (±SD) change of -66.81±72.63 µm, -66.76±60.71 µm for CSRT and -0.27±0.24 mm³ for macular volume (all p<0.001). Intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis.
The results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.
The results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.
To validate a deep learning (DL) algorithm (DLA) for 360° angle assessment on swept-source optical coherence tomography (SS-OCT) (CASIA SS-1000, Tomey Corporation, Nagoya, Japan).
This was a reliability analysis from a cross-sectional study. An independent test set of 39 936 SS-OCT scans from 312 phakic subjects (128 SS-OCT meridional scans per eye) was analysed. Participants above 50 years with no previous history of intraocular surgery were consecutively recruited from glaucoma clinics. Indentation gonioscopy and dark room SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle. For each subject, all images were analysed by a DL-based network based on the VGG-16 architecture, for gonioscopic angle-closure detection. Area under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators were calculated for the DLA (index test) against gonioscopy (reference standard).
Approximately 80% of thy' in future.Atrial fibrillation is a common chronic disease seen in primary care offices, emergency departments, inpatient hospital services, and many subspecialty practices. Atrial fibrillation care is complicated and multifaceted, and, at various points, clinicians may see it as a consequence and cause of multi-morbidity, as a silent driver of stroke risk, as a bellwether of an acute medical illness, or as a primary rhythm disturbance that requires targeted treatment. Primary care physicians in particular must navigate these priorities, perspectives, and resources to meet the needs of individual patients. This includes judicious use of diagnostic testing, thoughtful use of novel therapeutic agents and procedures, and providing access to subspecialty expertise. This review explores the epidemiology, screening, and risk assessment of atrial fibrillation, as well as management of its symptoms (rate and various rhythm control options) and stroke risk (anticoagulation and other treatments), and offers a model for the integration of the components of atrial fibrillation care.The inter-relationship between physical activity, sedentary behaviour and sleep (collectively defined as physical behaviours) is of interest to researchers from different fields. Each of these physical behaviours has been investigated in epidemiological studies, yet their codependency and interactions need to be further explored and accounted for in data analysis. Modern accelerometers capture continuous movement through the day, which presents the challenge of how to best use the richness of these data. In recent years, analytical approaches first applied in other scientific fields have been applied to physical behaviour epidemiology (eg, isotemporal substitution models, compositional data analysis, multivariate pattern analysis, functional data analysis and machine learning). A comprehensive description, discussion, and consensus on the strengths and limitations of these analytical approaches will help researchers decide which approach to use in different situations. In this context, a scientific workshop and meeting were held in Granada to discuss (1) analytical approaches currently used in the scientific literature on physical behaviour, highlighting strengths and limitations, providing practical recommendations on their use and including a decision tree for assisting researchers' decision-making; and (2) current gaps and future research directions around the analysis and use of accelerometer data. Advances in analytical approaches to accelerometer-determined physical behaviours in epidemiological studies are expected to influence the interpretation of current and future evidence, and ultimately impact on future physical behaviour guidelines.
Studies on subsequent anterior cruciate ligament (ACL) ruptures and career length in male professional football players after ACL reconstruction (ACLR) are scarce.
To investigate the second ACL injury rate, potential predictors of second ACL injury and the career length after ACLR.
Prospective cohort study.
Men's professional football.
118 players with index ACL injury were tracked longitudinally for subsequent ACL injury and career length over 16.9 years. Multivariable Cox regression analysis with HR was carried out to study potential predictors for subsequent ACL injury.
Median follow-up was 4.3 (IQR 4.6) years after ACLR. The second ACL injury rate after return to training (RTT) was 17.8% (n=21), with 9.3% (n=11) to the ipsilateral and 8.5% (n=10) to the contralateral knee. Significant predictors for second ACL injury were a non-contact index ACL injury (HR 7.16, 95% CI 1.63 to 31.22) and an isolated index ACL injury (HR 2.73, 95% CI 1.06 to 7.07). In total, 11 of 26 players (42%) with a non-contact isolated index ACL injury suffered a second ACL injury. RTT time was not an independent predictor of second ACL injury, even though there was a tendency for a risk reduction with longer time to RTT. Median career length after ACLR was 4.1 (IQR 4.0) years and 60% of players were still playing at preinjury level 5 years after ACLR.
Almost one out of five top-level professional male football players sustained a second ACL injury following ACLR and return to football, with a considerably increased risk for players with a non-contact or isolated index injury.
Almost one out of five top-level professional male football players sustained a second ACL injury following ACLR and return to football, with a considerably increased risk for players with a non-contact or isolated index injury.
To examine changes in the screening, diagnosis, treatment and management of drug-resistant tuberculosis (DRTB) patients, and investigate the impacts of DRTB-related policies on patients of different demographic and socioeconomic characteristics.
A retrospective cohort study using registry data, plus a survey on DRTB-related policies.
All prefecture-level Centres for Disease Control in Zhejiang Province, China.
Alongside the care cascade, we examined (1) reported number of presumptive DRTB patients; (2) percentage of presumptive patients with drug susceptibility testing (DST) records; (3) percentage of DRTB/rifampicin-resistant (RR) patients registered; (4) percentage of RR/multidrug-resistant TB (MDRTB) patients that received anti-DRTB treatment; and (5) percentage of RR/MDRTB patients cured/completed treatment among those treated. Multivariate logistic regressions were conducted to explore the impacts of DRTB policies after adjusting for other factors.
The number of reported presumptive DRTB patienld provide comprehensive support for migrants to complete treatment at their current place of residence.
The policy changes on DST and registration have effectively improved DRTB case finding and care. Nevertheless, challenges remain in servicing vulnerable groups such as migrants and improving equity in the access to TB care. Future policies should provide comprehensive support for migrants to complete treatment at their current place of residence.
