Management of muscle-invasive bladder cancer with radiation is associated with a 45% local relapse rate at 2 years. Concurrent treatment with mitomycin C and fluorouracil reduced recurrence to 33% ...and was not associated with increased late treatment-related toxicity.
Bladder cancer, with more than 385,000 new cases worldwide in 2008,
1
is a major cause of cancer complications. The median age at diagnosis is over 70 years, and since the tumor often is related to smoking, many patients have a substantial number of coexisting illnesses that pose risks for radical surgical approaches. Survival rates are poor for muscle-invasive bladder cancer, with around 45% of patients surviving for 5 years regardless of the type of treatment.
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–
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Although surgery is considered the standard therapy, considerable interest in bladder preservation has led to the use of radiotherapy as an alternative, particularly in . . .
To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder ...cancer.
In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years).
Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population.
In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.
Despite Spirochetales being a ubiquitous and medically important order of bacteria infecting both humans and animals, there is extremely limited information regarding their bacteriophages. Of the ...genus Treponema, there is just a single reported characterised prophage.
We applied a bioinformatic approach on 24 previously published Treponema genomes to identify and characterise putative treponemal prophages. Thirteen of the genomes did not contain any detectable prophage regions. The remaining eleven contained 38 prophage sequences, with between one and eight putative prophages in each bacterial genome. The prophage regions ranged from 12.4 to 75.1 kb, with between 27 and 171 protein coding sequences. Phylogenetic analysis revealed that 24 of the prophages formed three distinct sequence clusters, identifying putative myoviral and siphoviral morphology. ViPTree analysis demonstrated that the identified sequences were novel when compared to known double stranded DNA bacteriophage genomes.
In this study, we have started to address the knowledge gap on treponeme bacteriophages by characterising 38 prophage sequences in 24 treponeme genomes. Using bioinformatic approaches, we have been able to identify and compare the prophage-like elements with respect to other bacteriophages, their gene content, and their potential to be a functional and inducible bacteriophage, which in turn can help focus our attention on specific prophages to investigate further.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and ...60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.
The multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single ...control arm. MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally designed trials. Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive, advanced disease as quickly as possible. The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases.
STAMPEDE is an open-label, 5-stage, 6-arm randomised controlled trial using MAMS methodology for men with prostate cancer. It is the first trial of this design to use multiple arms and stages synchronously.
The practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials. These issues include the choice of intermediate and final outcome measures, sample size calculations and the impact of varying the assumptions, the process for moving between trial stages, stopping accrual to each trial arm and overall, and issues around perceived trial complexity.
It is possible to use the MAMS design to initiate and undertake large scale cancer trials. The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other researchers will use this exciting and efficient method to perform further randomised controlled trials.
ISRCTN78818544, NCT00268476.
There is a need to improve the outcomes for men with high‐risk localised, nodal or metastatic prostate cancer, or with aggressively relapsing disease after initial therapy for local disease. This ...group of men is currently managed with long‐term hormone therapy. Thus we aim to evaluate the toxicity and efficacy of three different systemic therapies (docetaxel, zoledronic acid and celecoxib) used alone or combined at the initiation of hormone manipulation for high‐risk prostate cancer. A novel statistical design (multi‐arm, multistage method) simultaneously tests multiple distinct strategies in parallel against a single control arm. The trial has several ‘stages’, from initial confirmation of safety to a phase III assessment of survival, with a series of intervening activity stages. This method provides a means of assessing several agents more quickly and efficiently, and allows inactive treatments to be dropped from further study at an early stage. STAMPEDE has been designed to address in parallel the activity and efficacy of these agents for this patient group. It is a flagship randomized clinical trial for academic research into prostate cancer in the UK. More than 500 patients have been recruited on schedule, confirming the acceptability of this complex trial design to patients and clinicians. The trial targets a population of ≈3000 patients.
STAMPEDE is a major new trial with a novel design applicable to the synchronous testing of several agents. It is hoped that the results will improve outcomes for patients with high‐risk prostate cancer. The design could be applicable to the study of new therapies in other cancer types. Continued efforts are required by the urological cancer community to maintain the excellent recruitment shown to date.
Acute Carpal Tunnel Syndrome Gillig, Jonathan D., MD; White, Stephen D., MD; Rachel, James Nicholas, MD
The Orthopedic clinics of North America,
July 2016, Letnik:
47, Številka:
3
Journal Article
Recenzirano
Acute carpal tunnel syndrome is a progressive median nerve compression leading to loss of two-point discrimination. Most cases encountered are in the emergency department following wrist trauma and ...distal radius fractures. Although rare, atraumatic etiologies have been reported and diligent evaluation of these patients should be performed. If missed or neglected, irreversible damage to the median nerve may result. Once diagnosed, emergent carpal tunnel release should be performed. If performed in a timely manner outcomes are excellent, often with complete recovery.
e18675
Background: It is well documented that LGBTQ+ cancer patients face severe challenges in accessing care and resources. Barriers are persistent despite recent advancements. Cancer clinical trial ...(CCT) participation rates for LGBTQ+ communities reflect this disparity. Understanding the reasons behind low participation rates and evaluating how LGBTQ+ specific experiences differ from the general population can help develop resources and programs that address the disparities in CCT participation, advancing LGBTQ+ health equity. Methods: In October 2022, CSC facilitated two virtual focus groups with 12 adults diagnosed with cancer and self-identifying as LGBTQ+. Participants were recruited from CSC’s Cancer Experience Registry (CER), representing wide gender and sexual orientation spectrums, a variety of cancer diagnosis and treatment trajectories, were 26-83 years of age, and a majority were college educated. A pre-screener survey collected sociodemographics to diversify the participant profile. Focus group data included participants' background, their experiences living with cancer as members of LGBTQ+ communities, and knowledge, attitudes, and experiences with CCTs. Transcripts were analyzed using deductive codes of sociodemographic information and inductive codes based on emergent themes. Results: LGBTQ+ patients reported: 1—Perceived institutional discrimination by healthcare providers in addressing their needs resulting in trust issues among patients; and 2—Relational and informational barriers block LGBTQ+ participation in CCTs. 19/21 screening survey respondents and 11/12 focus group participants had heard of CCTs, though none had participated. Each expressed a strong desire to help others and contribute to cancer research. However, patients doubted the medical ethics and personal benefits of CCTs, and most believed there are selective biases in recruitment. Conclusions: LGBTQ+ patients feel discriminated against when advocating for their health, identity, and rights, and struggle to trust their medical providers. Experiences of mistrust and discrimination inform LGBTQ+ patients’ perspective on and participation in CCTs. Findings suggest a need for 1—well-developed informational materials addressing the needs of LGBTQ+ communities; 2—better education and engagement of CCT teams on how to address those needs.
Intentional exploration, or elicitation, of patient values (who and what matters most) in the context of left ventricular assist devices (LVADs) can assist in identifying health preferences and care ...priorities. Yet, the values elicitation experiences of individuals post LVAD-implantation have been understudied, particularly among historically minoritized African American (AA)/Black and rural-dwelling individuals. Understanding the facilitators and barriers to values discussions among individuals from these groups is critical to addressing disparities in outcomes and optimizing patient-centered decision-making.
To identify facilitators and barriers to values discussions between patients with an LVAD, their family caregivers (FCGs), and the healthcare team.
Analysis of qualitative data from an ongoing convergent mixed methods study (January 2023-present) among AA/Black and rural-dwelling patients with an LVAD recruited from a large outpatient center in the U.S. South. Participants completed a semi-structured, in-person/telephone interview where questions were asked about their values elicitation experiences. Transcribed interviews were analyzed using a thematic analysis approach.
Fourteen participants ages 30-69 were interviewed. Patients were predominantly non-Hispanic AA/Black (n=12, 86%), male (n=9, 64%), and urban-dwelling (n=10, 71%). Patients reported previous values discussions with their FCGs (n=14, 100%) and healthcare team (n=10, 71%). Facilitators to discussions with FCGs and the healthcare team included a perceived close relationship, sharing similar values (e.g., belief in a higher power), and patient motivation to discuss their values (e.g., assertive personality). Barriers to discussions with FCGs included grief over loss of previously enjoyable activities (e.g., inability to engage in hobbies), FCG distress, and lack of time (e.g., acute illness); barriers to discussions with the healthcare team included previous conflict, receiving mixed messages about the treatment plan, perceived lack of time (e.g., brief appointments), and seeing different providers each visit.
Qualitative analyses of an ongoing mixed methods study found that facilitators of values discussions included a perceived close relationship, sharing similar values, and patient motivation to discuss their values. Barriers included grief over loss of previously enjoyable activities, FCG distress, lack of time, previous conflict, receiving mixed messages about the treatment plan, and seeing different providers each visit. Generating a comprehensive understanding of the values elicitation experiences of patients and their FCGs is critical to the development of interventions aimed at increasing values discussions between patients, FCGs, and the healthcare team. Future work is needed to understand facilitators and barriers to values discussions from the clinician perspective.
Acute carpal tunnel syndrome is a progressive median nerve compression leading to loss of two-point discrimination. Most cases encountered are in the emergency department following wrist trauma and ...distal radius fractures. Although rare, atraumatic etiologies have been reported and diligent evaluation of these patients should be performed. If missed or neglected, irreversible damage to the median nerve may result. Once diagnosed, emergent carpal tunnel release should be performed. If performed in a timely manner outcomes are excellent, often with complete recovery.
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