Klavsenkarlsson4975

To explore the experiences and perceptions of trial participants and healthcare professionals in the UK Frozen Shoulder Trial (UK FROST), a multicentre randomised controlled trial that compared manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR) with a 12-week early structured physiotherapy programme (ESP) in people with unilateral frozen shoulder referred to secondary care.

Nested qualitative study with semistructured interviews. We used constant comparison method to develop our themes.

This qualitative study was nested within the UK FROST.

44 trial participants (ESP 14; MUA 15; ACR 15), and 8 surgeons and 8 physiotherapists who delivered the treatments in the trial.

Trial participants found UK FROST treatments acceptable and satisfactory in terms of content, delivery and treatment benefits. Participants in all arms experienced improvements in pain, shoulder movements, and function. Participants said they would choose the same treatment that they received in the trial.Surgeonsld settings are suggested in future trials in the frozen shoulder.

International Standard Randomised Controlled Trial Register, ID ISRCTN48804508. IA Registered on 25 July 2014; Results.

International Standard Randomised Controlled Trial Register, ID ISRCTN48804508. Registered on 25 July 2014; Results.Early results from a phase II clinical trial show that the third-generation tyrosine kinase inhibitor ponatinib plus the bispecific T-cell engager blinatumomab can produce complete molecular remissions in most patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.Single-cell 3-D imaging was used to spatially and phenotypically profile a pediatric Wilms tumor.Macrophages and cancer cells interact to influence mesenchymal-like programs in glioblastomas.In early-stage breast cancer, ribociclib plus letrozole led to estrogen-independent resistance pathways.A massive study of ovarian cancer screening has determined that annual screening with ultrasound alone or CA125 testing and, if necessary, follow-up with ultrasound does not reduce mortality in the general population. Although more early cases came to light with screening, the increase was not large enough to yield a statistically significant survival improvement.

Breast cancer and cardiovascular diseases often share the same risk factors. It is increasingly important to identify risk factors for cardiovascular (CV) events in high-risk breast cancer patients and explore optimal treatment regimens.

Early HER2-positive breast cancer patients at our institution between January 1998 and October 2009 were reviewed. Primary outcome was late-severe-CV-event-free survival, and late severe CV events were defined as cardiovascular death, cardiomyopathy, symptomatic heart failure and myocardial infarction developing 2+ years after breast cancer diagnosis. Kaplan-Meier plots, Cox proportional hazard regressions, and restricted mean survival time were used to evaluate outcomes.

We identified 2,448 consecutive eligible patients with a median follow-up time of 111.0 months (interquartile range, 52.0-151.8 months). 136 patients had late severe CV events and 752 died of any cause (533 (70.9%) died of primary breast cancer; 12 (1.6%) died of cardiovascular disease). Hypertension ( better overall survival.

Improved risk stratification and predictive biomarkers of treatment response are needed for non-muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC.

Gene expression in NMIBC samples was profiled by NanoString nCounter, an RNA quantification platform, from two independent cohorts (

= 28,

= 50); targeted panel sequencing was performed in a subgroup (

= 50). Gene signatures were externally validated using two RNA sequencing datasets of NMIBC tumors (

= 438,

= 73). Established molecular subtype classifiers and novel gene expression signatures were assessed for associations with clinicopathologic characteristics, somatic tumor mutations, and treatment outcomes.

Molecular subtypes distinguished between low-grade Ta tumors with FGFR3 mutations and overexpression (UROMOL-class 1) and tumors with more aggressive clinicopathologic characteristics (UROMOL-classes 2 and 3), which were significantly enriched with TERT promoteron. Integrated transcriptomic and exome sequencing should improve treatment selection in NMIBC.

Mutations in

(

) predict lack of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). However, it is unclear if all

mutations have similar impact, and atypical mutations beyond those in standard guidelines exist.

We reviewed 7 tissue and 1 cell-free DNA cohorts of 9,485 patients to characterize atypical

variants. Using an

cell-based assay (functional annotation for cancer treatment), Ba/F3 transformation, and

xenograft models of transduced isogenic clones, we assessed signaling changes across mutations.

exon 2, extended

, and atypical

mutations were noted in 37.8%, 9.5%, and 1.2% of patients, respectively. Among atypical variants,

L19F, Q22K, and D33E occurred at prevalence ≥0.1%, whereas no

codon 117/146 and only one

codon 59 mutation was noted. Atypical

mutations had worse overall survival than

wild-type mCRC (HR, 2.90; 95% confidence interval, 1.24-6.80;

= 0.014). We functionally characterized 114 variants with the FACT assay. All

exon 2 and extended

mutations appeared activating. Of 57 atypical

variants characterized, 18 (31.6%) had signaling below wild-type, 23 (40.4%) had signaling between wild-type and activating control, and 16 (28.1%) were hyperactive beyond the activating control. Ba/F3 transformation (17/18 variants) and xenograft model (7/8 variants) validation was highly concordant with FACT results, and activating atypical variants were those that occurred at highest prevalence in clinical cohorts.

We provide best available evidence to guide treatment when atypical

variants are identified.

L19F, Q22K, D33E, and T50I are more prevalent than many guideline-included

variants and functionally relevant.

We provide best available evidence to guide treatment when atypical RAS variants are identified. KRAS L19F, Q22K, D33E, and T50I are more prevalent than many guideline-included RAS variants and functionally relevant.