Developing a curriculum for advanced fellowship training in complex cancer for the UK.

Aim: Surgery for complex colorectal cancer is elaborate: preoperative assessment, patient selection, radiological interpretation, operative strategy, operative technical skills, operative standardization, postoperative care and management of complications are all critical components. Given this complexity, training that encompasses all these crucial aspects to generate suitably edified surgeons is essential. To date, no curriculum exists to guide training in advanced and recurrent pelvic malignancy, particularly for complex colorectal cancer.

Genetic, epigenetic and environmental factors in diverticular disease: systematic review.

Background: Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop diverticulitis in their lifetime. Many patients present emergently, suffer high morbidity rates and require substantial healthcare resources.

Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress.

Impacts of Covid-19 on mental health service provision in the Western Cape, South Africa: The MASC study.

In the context of an already large treatment gap in South Africa, this study aimed to examine how Covid-19 and the related lockdown measures affected the availability, accessibility, quality, and continuity of mental health services in the Western Cape province in South Africa. A mixed-methods design was employed, using narrative surveys, quantitative surveys, and qualitative semi-structured interviews, with 17 public mental health providers, and secondary data from the District Health Information System. We analysed and combined the data using descriptive statistics, template analysis and methodological triangulation.

Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells.

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalisation in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs) .

Clinical management of high-output stoma: a systematic literature review and meta-analysis.

Purpose: High output is a common complication after stoma formation. Although the management of high output is described in the literature, there is a lack of consensus on definitions and treatment. Our aim was to review and summarise the current best evidence.

Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory.

Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.

Introduction: Post translational modification of proteins plays a significant role in immune recognition. In particular the modification of arginine to citrulline which is mediated by PAD enzymes is increased during cellular stress (autophagy) which permits the presentation of modified epitopes upon MHC class II molecules for recognition by CD4 T cells. Citrullination also occurs in tumour cells as a result of continuous environmental stresses and increased autophagy.

Long-term follow-up of bilateral gracilis reconstruction following extra-levator abdominoperineal excision.

Introduction: Colorectal operations such as an extra-levator abdominoperineal (elAPE) excision for locally advanced or recurrent cancer create a significant perineal tissue deficit. Options for perineal reconstruction include bilateral pedicled gracilis muscle flaps (BPGMF). Fashioning the gracili into a 'weave' creates a muscular sling that supports pelvic contents and is a novel technique.

What should be included in case report forms? Development and application of novel methods to inform surgical study design: a mixed methods case study in parastomal hernia prevention.

Objectives: To describe the development and application of methods to optimise the design of case report forms (CRFs) for clinical studies evaluating surgical procedures, illustrated with an example of abdominal stoma formation.

Design: (1) Literature reviews, to identify reported variations in surgical components of stoma formation, were supplemented by (2) intraoperative qualitative research (observations, videos and interviews), to identify unreported variations used in practice to generate (3) a 'long list' of items, which were rationalised using (4) consensus methods, providing a pragmatic list of CRF items to be captured in the Cohort study to Investigate the Prevention of parastomal HERnias (CIPHER) study.

Setting: Two secondary care surgical centres in England.

Black Men Who Have Sex with Men with HIV and Providers in HIV Care Settings Reflect on Stigma Reducing Strategies to Promote Engagement in Health Care.

Black men who have sex with men (BMSM) with HIV face significant challenges in accessing health care, including routine HIV care and behavioral health care due in part to perceived stigma in health care settings. This study examined the perspectives of BMSM with HIV and health care providers of how stigma experiences can affect health care access to both clinical and behavioral health support services. We explored how providers can mitigate stigma practices and improve health care experiences for BMSM with HIV, which may ultimately improve engagement in care.

An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease.

Background: The ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriCol™), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery.

Methods: Using National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020-May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory.

PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy.

Background: The enzymatic conversion of arginine to citrulline is involved in gene and protein regulation and in alerting the immune system to stressed cells, including tumor cells. Nucleophosmin (NPM) is a nuclear protein that plays key roles in cellular metabolism including ribosome biogenesis, mRNA processing and chromatin remodeling and is regulated by citrullination. In this study, we explored if the same citrullinated arginines within NPM are involved in gene regulation and immune activation.

Quality of life in restorative versus non-restorative resections for rectal cancer: systematic review.

Background: Low rectal cancers could be treated using restorative (anterior resection, AR) or non-restorative procedures with an end/permanent stoma (Hartmann's, HE; or abdominoperineal excision, APE). Although the surgical choice is determined by tumour and patient factors, quality of life (QoL) will also influence the patient's future beyond cancer. This systematic review of the literature compared postoperative QoL between the restorative and non-restorative techniques using validated measurement tools.

Preoperative assessment and optimisation for pelvic exenteration in locally advanced and recurrent rectal cancer: A review.

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning.

Debate: Is there a true global children and young people mental health crisis? Fact or Fiction: A South African Perspective.

The article seeks to discuss the complexities that prevail in South Africa in attempting to understand the debate about whether there is a true global children and young people mental health crisis in the country. In the absence of reliable and current epidemiological data and prevalence studies, assumptions can only be made about the extent of the crisis when considering the prevailing social determinants of mental disorders. The lack of investment, limited child and adolescent mental health resources, and inadequate access to treatment complicate this crisis as many children and young people go untreated.

Homocitrullination of lysine residues mediated by myeloid-derived suppressor cells in the tumor environment is a target for cancer immunotherapy.

Background: Homocitrullination is the post-translational modification of lysine that is recognized by T cells.

Methods: This study identified homocitrullinated peptides from aldolase, enolase, cytokeratin and binding immunoglobulin protein and used human leukocyte antigen (HLA) transgenic mice to assess immunogenicity by enzyme-linked immunosorbent spot assay. Vaccine efficacy was assessed in tumor therapy studies using HLA-matched B16 melanoma expressing constitutive or interferon γ (IFNγ)-inducible major histocompatibility complex class II (MHC-II) as represented by most human tumors.

Protocol for the UK cohort study to investigate the prevention of parastomal hernia (the CIPHER study).

Aim: Abdominal surgery sometimes necessitates the creation of a stoma, which can cause future complications including parastomal hernia (PSH), an incisional hernia adjacent to and related to the stoma. PSH affects approximately 40% of patients within 2 years of stoma formation. Complications of PSH reduce a patient's quality of life and can be severe (e.

Root-cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease.

Background: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice.

Aim: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC.

Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses.

Background: Stress-induced post-translational modifications occur during autophagy and can result in generation of new epitopes and immune recognition. One such modification is the conversion of arginine to citrulline by peptidylarginine deiminase enzymes.

Methods: We used Human leukocyte antigen (HLA) transgenic mouse models to assess the immunogenicity of citrullinated peptide vaccine by cytokine Enzyme linked immunosorbant spot (ELISpot) assay.

Engineering the Human Fc Region Enables Direct Cell Killing by Cancer Glycan-Targeting Antibodies without the Need for Immune Effector Cells or Complement.

Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to noncovalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization.