International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Barriers and facilitators to giving prehabilitation advice by clinical nurse specialists and advanced nurse practitioners in oncology patients.

PURPOSE: This is the second article in this series on the knowledge, attitudes and beliefs of clinical nurse specialists (CNSs) and ANPs (advanced nurse practitioners) regarding prehabilitation advice in oncology patients, exploring the barriers and facilitators to giving prehabilitation advice by CNSs and ANPs in oncology patients. METHODS: A Cross-sectional online questionnaire opens for 3 months to establish the knowledge, attitudes and beliefs of ANPs and CNSs to prehabilitation disseminated through professional organisations and social media. RESULTS: The questionnaire gained (n = 415) responses. Prehabilitation advice was routinely given by 89% (n = 371) of respondents. Many (60%) identified a lack of guidance and referral processes as a barrier to giving prehabilitation advice; this corresponded between respondents' confidence to give prehabilitation advice and subsequent referrals (< 0.001). Other factors included time (61%), a lack of patient interest (44%) and limited relevance to patients (35%). CONCLUSION: The implementation of standardised nurse prehabilitation advice resources would enable CNSs and ANPs to provide personalised prehabilitation advice in their consultations.

SafeFit Trial: virtual clinics to deliver a multimodal intervention to improve psychological and physical well-being in people with cancer. Protocol of a COVID-19 targeted non-randomised phase III trial.

INTRODUCTION: The impact of the COVID-19 pandemic (caused by the SARS-CoV-2 virus) on individuals with cancer has been profound. It has led to increased anxiety, distress and deconditioning due to reduced physical activity. We aim to investigate whether SafeFit, a multimodal intervention of physical activity, nutrition and psychological support delivered virtually by cancer exercise specialists (CES), can improve physical and emotional functionings during the COVID-19 pandemic. METHODS AND ANALYSIS: A phase III non-randomised intervention trial, target recruitment of 1050 adults with suspected or confirmed diagnosis of cancer. All recruited participants will receive the multimodal intervention delivered by CES for 6 months. Sessions will be delivered 1-to-1 using telephone/video conferencing consultations. CES will work with each participant to devise a personalised programme of (1) physical activity, (2) basic dietary advice and (3) psychological support, all underpinned by behaviour change support. PRIMARY OUTCOME: Physical and emotional functioning as measured by the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30). SECONDARY OUTCOMES: overall quality of life measured by EORTC-QLQ-C30 and EQ-5D-5L, health economics, patient activation, self-efficacy to self-manage chronic disease, distress, impact of COVID-19 on emotional functioning, self-reported physical activity, functional capacity and nutrition. Adherence to the intervention will also be measured and a process evaluation conducted. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (reference number 20/NW/0254). Results of this trial will be disseminated through publication of peer-reviewed articles, presentations at scientific conferences, and to the public and people with cancer in collaboration with our patient and public involvement representatives and partners. TRIAL REGISTRATION NUMBER: NCT04425616.

Prognostic significance of low muscle volume in patients undergoing surgery for oesophageal cancer.

BACKGROUND & AIMS: This study aimed to determine the prognostic significance of low muscle volume (LMV) Bioelectrical Impedance Analysis (BIA), defined skeletal muscle index (SMI, Kg/m2 male ≤8.75, female ≤5.75) in patients undergoing potentially curative surgery for Oesophageal Cancer (OC). METHODS: A prospective study of 122 patients diagnosed with OC [median age 65 yr, 104 male, 65 neoadjuvant therapy] who underwent preoperative BIA (Maltron Bioscan 920). Primary outcome measure was Overall Survival (OS). RESULTS: LMV was identified in 11 (9.0%) of patients, which was associated with low lean muscle mass (27.3 vs. 31.1 kg, p = 0.012), low body fat (8.8 vs.19.3 kg, p < 0.001), and greater total body water (72.2 vs. 62.2%, p = 0.001), and more open & close laparotomies (36.4 vs. 8.1%, p = 0.012). Median and 5-year OS was 16 months and 18.2% in LMV patients, compared with 51 months and 52.4% in non-sarcopenic patients (p = 0.002). On multivariable analysis of pre-operative variables, only LMV (HR 2.75; 95% CI 1.33-5.66, p = 0.006) was associated with OS. CONCLUSION: BIA is an important prognostic indicator in OC and focused pre-habilitation consequently has strong potential.

Fit for Cancer Treatment: a prospective feasibility study of primary care initiated prehabilitation for patients with suspected cancer.

BACKGROUND: Risk profile assessment and corrective interventions using optimisation of health status and prehabilitation represent an important strategy in the management of patients with a suspected cancer diagnosis. AIM: To determine the feasibility of pre-treatment optimisation and prehabilitation commenced at index primary care consultation, to improve patients' preparation for treatment by maximising the time available. DESIGN & SETTING: Between January 2015 and May 2016, 195 patients presenting to 12 GP practices were deemed eligible to enter the study, of which 189 (96.9%, median age 60 [21-91] years and 65 months; 124 female) were recruited and consented to the prehabilitation bundle. METHOD: All patients were simultaneously referred to secondary care using urgent suspected cancer (USC) pathways. The primary outcome measures were definitive diagnosis and treatment plan. RESULTS: Fifteen patients (7.9%) were diagnosed with cancer (three breast, three colon, two lung, two skin [one melanoma, one sarcoma], one tonsil, one vocal cord, one pancreas, one prostate, one ependymoma) and 62 were diagnosed with other significant medical conditions (47 gastrointestinal, 13 sepsis, two respiratory) requiring secondary care assessment and treatment. Of the 15 patients with cancer, 11 (73.3%) underwent potentially curative treatment, and four (26.7%) palliative treatment. Of the total study cohort, 84 (44%) required a form of optimisation in primary care, and patients with cancer were more likely to require optimisation than others (n = 10 [63%] versus n = 74 [43%], χ2 9.384, P = 0.002). CONCLUSION: One in 12 primary care USC patients had cancer (5.6% receiving potentially curative treatment), one in three had other systemic health issues, and overall two in five benefited from healthcare intervention. Primary care optimisation was feasible and associated with important allied health benefits.

Collaboration to transform care.

Transforming Care is an improvement initiative introduced at Betsi Cadwaladr University Health Board in October 2010. The health board collaborated with a university to develop a degree module to support its implementation. This article describes the delivery and evaluation of the module, and how Transforming Care is helping to unite a newly formed organisation.

Prospective multicentre randomised controlled trial of early enteral nutrition for patients undergoing major upper gastrointestinal surgical resection.

BACKGROUND & AIMS: The evidence in support of Early Enteral Nutrition (EEN) after upper gastrointestinal surgery is inconclusive. The aim of this study was to determine if EEN improved clinical outcomes and shortened length of hospital stay. METHODS: Open, prospective multicentre randomised controlled trial within a regional UK Cancer Network. One hundred and twenty-one patients with suspected operable upper gastrointestinal cancer (54 oesophageal, 38 gastric, 29 pancreatic) were studied. Patients were randomised to receive EEN (n = 64) or Control management postoperatively (nil by mouth and IV fluid, n = 57). Analysis was based on intention-to-treat and the primary outcome measure was length of hospital stay. RESULTS: Operative morbidity was less common after EEN (32.8%) than Control management (50.9%, p = 0.044), due to fewer wound infections (p = 0.017), chest infections (p = 0.036) and anastomotic leaks (p = 0.055). Median length of hospital stay was 16 days (IQ = 9) after EEN compared with 19 (IQ = 11) days after Control management (p = 0.023). CONCLUSIONS: EEN was associated with significantly shortened length of hospital stay and improved clinical outcomes. These findings reinforce the potential benefit of early oral nutrition in principle and as championed within enhanced recovery after surgery programmes, and such strategies deserve further research in the arena of upper GI surgery.

Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.

Mammalian genomes contain many repetitive elements, including long terminal repeats (LTRs), which have long been suspected to have a role in tumorigenesis. Here we present evidence that aberrant LTR activation contributes to lineage-inappropriate gene expression in transformed human cells and that such gene expression is central for tumor cell survival. We show that B cell-derived Hodgkin's lymphoma cells depend on the activity of the non-B, myeloid-specific proto-oncogene colony-stimulating factor 1 receptor (CSF1R). In these cells, CSF1R transcription initiates at an aberrantly activated endogenous LTR of the MaLR family (THE1B). Derepression of the THE1 subfamily of MaLR LTRs is widespread in the genome of Hodgkin's lymphoma cells and is associated with impaired epigenetic control due to loss of expression of the corepressor CBFA2T3. Furthermore, we detect LTR-driven CSF1R transcripts in anaplastic large cell lymphoma, in which CSF1R is known to be expressed aberrantly. We conclude that LTR derepression is involved in the pathogenesis of human lymphomas, a finding that might have diagnostic, prognostic and therapeutic implications.

The Pu.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis.

The Ets family transcription factor PU.1 is crucial for the regulation of hematopoietic development. Pu.1 is activated in hematopoietic stem cells and is expressed in mast cells, B cells, granulocytes, and macrophages but is switched off in T cells. Many of the transcription factors regulating Pu.1 have been identified, but little is known about how they organize Pu.1 chromatin in development. We analyzed the Pu.1 promoter and the upstream regulatory element (URE) using in vivo footprinting and chromatin immunoprecipitation assays. In B cells, Pu.1 was bound by a set of transcription factors different from that in myeloid cells and adopted alternative chromatin architectures. In T cells, Pu.1 chromatin at the URE was open and the same transcription factor binding sites were occupied as in B cells. The transcription factor RUNX1 was bound to the URE in precursor cells, but binding was down-regulated in maturing cells. In PU.1 knockout precursor cells, the Ets factor Fli-1 compensated for the lack of PU.1, and both proteins could occupy a subset of Pu.1 cis elements in PU.1-expressing cells. In addition, we identified novel URE-derived noncoding transcripts subject to tissue-specific regulation. Our results provide important insights into how overlapping, but different, sets of transcription factors program tissue-specific chromatin structures in the hematopoietic system.

Genome analysis shows a common evolutionary origin for the dominant strains of Mycobacterium tuberculosis in a UK South Asian community.

We have investigated the Mycobacterium tuberculosis strain types present in the South Asian population of the UK, in which tuberculosis is particularly prevalent. In contrast to the widespread Beijing strains which have the variable number tandem repeats (VNTR) profile 42435, isolates with the VNTR profile 42235, jointly with 02335 or 42234 profiles, appear more frequently in tuberculosis patients of South Asian ethnic origin (SA-strains) in the UK than in any other ethnic group. Using microarray-based comparative genomics to distinguish total or partially deleted genes, we found that three of the common deleted regions in the SA-strains were identical to some deleted genes in the strain CH, which caused an outbreak among South Asian patients in Leicester in 2001 but were different from genomic deletions found in Beijing/W strains. Analysis of some of the deleted regions revealed differences in comparison to the strain CH including the polymorphism in some of the PE/PPE and Esat-6 genes, which may be responsible for the diversity of antigenic variation or differences in the activation of the host immune response. Interrupted genes or the replacement by insertion elements was confirmed in some of the deleted genomic regions. Our results are consistent with the hypothesis that the SA-strains may present common features, implying a common origin for this group of strains.

Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

Global distribution of Mycobacterium tuberculosis spoligotypes.

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11708 patterns from as many clinical isolates originating from more than 90 countries. The 11708 spoligotypes were clustered into 813 shared types. A total of 1300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.

The prevalence of Chlamydia trachomatis in fresh tissue specimens from patients with ectopic pregnancy or tubal factor infertility as determined by PCR and in-situ hybridisation.

The prevalence of chlamydial DNA determined by PCR and in-situ hybridisation (ISH) in fresh tissue specimens (endometrium, fallopian tube and ovary) was investigated in 33 women presenting with ectopic pregnancy (EP), 14 women with tubal factor infertility (TFI) and 50 control patients from the UK and the West Indies. In the UK EP group, chlamydial DNA was detected by PCR in 56% of patients; similar results were found in the Trinidad EP group (67%). In the TFI group, chlamydial DNA was detected in (71%) of patients by PCR. The detection of Chlamydia trachomatis DNA by ISH was highest in the TFI group (43%). Women presenting with EP and TFI showed evidence of previous or current genital C. trachomatis infection, underlining the importance of this microorganism in the development of these conditions. Importantly, chlamydial DNA could be detected in DNA preparations from the endometrium, fallopian tube and ovary of EP and TFI patients at the time of surgery.