Publications by authors named "J Larkin"

976 Publications

Sigmoid volvulus: definitive surgery is safe and should be considered in all instances.

Ir J Med Sci 2021 Jul 29. Epub 2021 Jul 29.

Department of Colorectal Surgery, St James's Hospital, Dublin 8, Ireland.

Background: Acute sigmoid volvulus (ASV) represents a small but significant portion of cases of large bowel obstruction, especially in the elderly and co-morbid. Given the characteristics of the patient cohort most commonly affected, a non-operative/conservative approach is often undertaken but is associated with a high rate of recurrence.

Objective: We sought to evaluate outcomes for those patients who underwent non-operative management, emergency surgery or staged, semi-elective surgery following decompression for ASV at our institution.

Methods: Hospital in-patient enquiry (HIPE) data were used to identify all patients who presented with sigmoid volvulus between January 2005 and June 2020 inclusive. Patient notes were interrogated, including surgical and endoscopic procedures performed. Patient demographics and co-morbidities were recorded.

Results: Thirty-nine patients were treated over a 15-year period with a mean age of 73 years at first presentation (range 36-93). Twenty-two patients (56%) had just a single admission for ASV with three deaths in this group. Seventeen patients (44%) had more than one admission with volvulus due to recurrence after a decompression-only strategy on the index admission. Of these, three succumbed to complications of their subsequent episodes of volvulus. Twenty-five patients underwent surgical intervention (fifteen on, or shortly following, their first admission and ten following at least two admissions for ASV). The overall mortality in the operative group was 2/25 (8%) with both deaths in those undergoing emergency surgeries. Five patients were treated successfully with endoscopic measures alone and had required no further interventions at the time of compiling data.

Conclusion: There is a high recurrence rate following non-operative management of acute sigmoid volvulus and consequently, a cumulative increase in the attendant significant morbidity and mortality with subsequent episodes. Given the relatively low complication rate of definitive surgery, even in those patients perceived to be high risk, we contend that all patients should be considered for early surgery to prevent the likely recurrence of sigmoid volvulus.
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http://dx.doi.org/10.1007/s11845-021-02713-0DOI Listing
July 2021

Selective blood-brain barrier permeabilisation of brain metastases by a type-1 receptor selective tumour necrosis factor mutein.

Neuro Oncol 2021 Jul 23. Epub 2021 Jul 23.

Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.

Background: Metastasis to the brain is a major challenge with poor prognosis. The blood-brain barrier (BBB) is a significant impediment to effective treatment, being intact during the early stages of tumour development and heterogeneously permeable at later stages. Intravenous injection of tumour necrosis factor (TNF) selectively induces BBB permeabilisation at sites of brain micrometastasis, in a TNF type-1 receptor (TNFR1) dependent manner. Here, to enable clinical translation, we have developed a TNFR1-selective agonist variant of human TNF that induces BBB permeabilisation, whilst minimising potential toxicity.

Methods: A library of human TNF muteins (mutTNF) were generated and assessed for binding specificity to mouse and human TNFR1/2, endothelial permeabilising activity in vitro, potential immunogenicity and circulatory half-life. The permeabilising ability of the most promising variant was assessed in vivo in a model of brain metastasis.

Results: The primary mutTNF variant showed similar affinity for human TNFR1 than wild-type human TNF, similar affinity for mouse TNFR1 as wild-type mouse TNF, undetectable binding to human/mouse TNFR2, low potential immunogenicity and permeabilisation of an endothelial monolayer. Circulatory half-life was similar to mouse/human TNF and BBB permeabilisation was induced selectively at sites of micrometastases in vivo, with a time window of ≥24h and enabling delivery of agents within a therapeutically-relevant range (0.5-150kDa), including the clinically approved therapy, trastuzumab.

Conclusions: We have developed a clinically-translatable mutTNF that selectively opens the BBB at micrometastatic sites, whilst leaving the rest of the cerebrovasculature intact. This approach will open a window for brain metastasis treatment that currently does not exist.
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http://dx.doi.org/10.1093/neuonc/noab177DOI Listing
July 2021

A protocol for the evaluation of the process and impact of embedding formal and experiential Public and Patient Involvement training in a structured PhD programme.

J Comorb 2021 Jan-Dec;11:26335565211024793. Epub 2021 Jun 28.

PPI Ignite Network, National University of Ireland Galway, Galway, Ireland.

Background: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD scholars. The importance of providing early career researchers with appropriate education and training to develop skills to conduct meaningful involvement has been articulated. The Collaborative Doctoral Award in MultiMorbidity (CDA-MM) PhD programme embedded formal PPI training as a postgraduate education component. Four PhD scholars taking part in the CDA-MM established a PPI panel comprising people, and carers of people, living with multimorbidity (≥2 chronic conditions), presenting an opportuning for experiential PPI training. The proposed study aims to evaluate the process and impact of formal and experiential PPI training during a PhD programme.

Design: Embedding PPI training in a PhD programme is a novel approach. This evaluation will include a process evaluation to provide an understanding of the workings of the PPI panel and explore the experiences of key stakeholders involved, and an impact evaluation to assess the impact of embedding PPI training in a PhD programme. This study is a longitudinal mixed-methods evaluation, conducted over 24 months. Participants include PhD scholars, PPI contributors and PhD supervisors. An independent researcher not aligned with the CDA-MM will lead the evaluation. Data collection methods include focus groups, individual interviews, an impact log and group reflections. Qualitative data will be analysed using thematic and content analysis and quantitative data will be analysed using descriptive statistics.

Discussion: This evaluation will report the learnings from embedding formal and experiential PPI training and education across a PhD programme.
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http://dx.doi.org/10.1177/26335565211024793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243087PMC
June 2021

Severe cutaneous adverse reaction post Covid-vaccine and immunotherapy- a second hit?

Clin Exp Dermatol 2021 Jul 14. Epub 2021 Jul 14.

Department of Dermatology, Chelsea and Westminster Hospital.

Dear Editor, A 62-year-old female with metastatic melanoma presented with shortness of breath four days after her fourth cycle of combination checkpoint inhibitor therapy (CPI) (nivolumab and ipilimumab) having previously received 12 months of adjuvant nivolumab 14 months earlier. Subsequent investigations confirmed CPI related myocarditis. She also described new onset of symptoms consistent with Raynaud's. Her past medical history included recurrent migraines for which she took propranolol. She was admitted to hospital, and received two 500mg doses of intravenous methylprednisolone, and commenced on a reducing course or oral prednisolone (1mg/kg), lansoprazole and co-trimoxazole prophylaxis. Blood tests initially revealed a negative anti-nuclear antibody, lupus anticoagulant and anticardiolipin antibodies with normal complement levels and rheumatoid factor. However repeat bloods six weeks later revealed a positive ANA and a very mildly positive extractable nuclear antigen (anti-SSA52/Ro autoantibody) by rheumatology did not identify any underlying connective tissue disease and concluded that the Raynaud's was likely to be secondary to the CPI.
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http://dx.doi.org/10.1111/ced.14852DOI Listing
July 2021
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