Publications by authors named "Sarah Mitchell"

One-week protein restriction (PR) limits ischemia-reperfusion (IR) damages and improves metabolic fitness. Similarly, longer-term calory restriction results in increased lifespan, partly via reduced insulin-like growth factor (IGF)-1. However, the influence of short-term PR on IGF-1 and its impact on IR are unknown.

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Communication can be a challenge for a significant minority of the population. Those with intellectual disability, autism, or Stroke survivors can encounter significant problems and stigma in their communication abilities leading to worse health and social outcomes. SpeechMatch (https://www.

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Background: Nearly 25% of people with intellectual disability (PwID) have epilepsy compared to 1% of the UK general population. PwID are commonly excluded from research, eventually affecting their care. Understanding seizures in PwID is particularly challenging because of reliance on subjective external observation and poor objective validation.

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Background: Guidance and principles for involving the public in research or service planning exist but are not specific to the needs of parents of children with life-limiting conditions or bereaved parents.

Aim: Review the evidence on involving parents of children with life-limiting conditions and bereaved parents in research, service planning and advocacy, and use this to develop best practice guidance.

Methods: Rapid review following the Cochrane Rapid Reviews Methods Group Guidance.

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Background: Persistent immune activation is linked to elevated cardiovascular diseases in people with HIV on antiretroviral therapy. The fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts cardiovascular disease risk in people without HIV. Whether FAI is associated with immune activation is unknown.

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The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for healthcare professionals. The 2023 AACR Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection, intervention, and reduce morbidity associated with such neoplasms. In this paper, we review several of the rare conditions discussed in this workshop.

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Article Synopsis
  • The study explores the Compassionate Cities initiative, which aims to enhance health-promotive palliative care and foster community support during death, dying, and bereavement.
  • Data was collected through interviews, document reviews, and observations in a UK Compassionate City, focusing on the experiences of its leadership during the initiative's rollout.
  • Key themes identified include the importance of having the right model and people, building community support systems for grief, and the critical role of leadership and communication in the initiative's success.
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PTEN hamartoma tumor syndrome (PHTS), DICER1-related tumor predisposition (DICER1) and tuberous sclerosis complex (TSC) are rare conditions which each increase risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection and multidisciplinary care. In this manuscript, we present updated surveillance recommendations and considerations for children and adolescents with PHTS, DICER1 and TSC and provide suggestions for further research in each of these conditions.

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  • * In a Phase II clinical trial, 27 patients received entinostat followed by nivolumab, resulting in an objective response rate of 11% and a median response duration of over 10 months, although the primary endpoint for overall effectiveness was not reached.
  • * The combination treatment led to significant immune profile changes, including increased dendritic cell activity and enhanced inflammatory response, suggesting potential for improving treatment strategies in PDA despite
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Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice.

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Background: People with intellectual disability (PwID) and epilepsy have increased premature and potentially preventable mortality. This is related to a lack of equitable access to appropriate care. The Step Together guidance and toolkit, developed with patient, clinical, charity and commissioning stakeholders, allows evaluation and benchmarking of essential epilepsy service provision for PwID in eight key domains, at a care system level.

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  • Polypharmacy, defined as the use of five or more medications, is common in older adults and can lead to serious health issues like cognitive decline, falls, and higher mortality rates.
  • A study was conducted on male mice to analyze the effects of both polypharmacy and the strategy of deprescribing (gradually reducing medications) to see how it impacts liver function and related proteins.
  • The results showed that polypharmacy caused significant changes in liver protein expression related to immunity and metabolism, while deprescribing had both reversing effects and introduced new changes that could impact geriatric health outcomes.
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Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.

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  • Immune-related adverse events (irAEs) pose significant risks for patients receiving immune checkpoint inhibitors (ICIs), highlighting the need to identify patients at higher risk and develop strategies to manage these complications.
  • An observational study involving 111 patients found that 40.5% experienced symptomatic irAEs, with higher rates linked to combination ICI therapy and pre-existing autoimmune disorders.
  • Early increases in specific cytokines and T helper cell populations were associated with developing severe irAEs, indicating potential biomarkers for monitoring and targeting therapeutic interventions.
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  • DICER1-related tumor predisposition is linked to an increased risk of both benign and malignant tumors, prompting the need for guidelines on testing and imaging for affected individuals.
  • A study enrolled participants from various registries and identified 713 individuals with germline DICER1 variants, leading to the diagnosis of multiple cases of pleuropulmonary blastoma (PPB) and ovarian Sertoli-Leydig cell tumors (SLCT).
  • The findings suggest that early imaging and surveillance can help detect PPB and may lower the risk of advanced disease, leading to recommendations for earlier ovarian surveillance beginning at the detection of DICER1 variants.
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  • This study is about helping doctors and surgeons find the best ways to diagnose and treat skin cancers in kids and teenagers, especially types like cutaneous melanoma and atypical Spitz tumors.
  • A group of 33 skin cancer specialists from different fields worked together and used research to come up with their recommendations.
  • They suggested specific ways to perform surgeries, the importance of classifying tumors correctly, and rules about how much tissue to remove around suspicious areas.
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  • Neurofibromatosis type 1 (NF1) and Noonan syndrome, classified under RASopathies, disrupt the RAS-MAPK pathway and present diverse clinical features across multiple body systems.
  • Children with RASopathies face a higher risk of developing both benign and malignant tumors compared to the general population, necessitating careful medical management.
  • Recent clinical trials have shown that targeted therapies can benefit low-grade and benign tumors, emphasizing the need for collaborative care among pediatric oncologists, neurologists, and other healthcare professionals based on updated guidelines from the 2023 AACR Childhood Cancer Predisposition Workshop.
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Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys.

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Dietary restriction of the sulfur-containing amino acids methionine and cysteine (SAAR) improves body composition, enhances insulin sensitivity, and extends lifespan; benefits seen also with endurance exercise. Yet, the impact of SAAR on skeletal muscle remains largely unexplored. Here we demonstrate that one week of SAAR in sedentary, young, male mice increases endurance exercise capacity.

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Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known.

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Background: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma.

Aim: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use.

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Background: Inequalities in access to palliative and end of life care are longstanding. Integration of primary and palliative care has the potential to improve equity in the community. Evidence to inform integration is scarce as research that considers integration of primary care and palliative care services is rare.

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Objective: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT.

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