CCC publication: MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-alpha, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial

Citation: Clinical cancer research: an official journal of the American Association for Cancer Research. 2020, 26(15), 3936-946

Author: Sarker D.; Spicer J.; Hunter S.; Kwatra V.; Lloyd P.; Plummer R.; Meyer T.; Sodergren M.H. (mikael.sodergren@imperial.ac.uk); Basu B.; Chee C.E.; Huang K.-W.; Palmer D.H.; Ma Y.T.; Evans T.R.J.; Spalding D.R.C.; Pai M.; Sharma R.; Pinato D.J.; Nicholls J.P.; Reebye V.; Andrikakou P.; Collin D.; Nutbrown R.; Glenny H.; Fairbairn S.; Voutila J.; Dorman S.; Felstead S.; Vasara J.; Habib R.; Wood C.; Blakey D.C.; Habib N.; Saetrom P.; Huber H.E.; Rossi J.J.

Abstract: PURPOSE: Transcription factor C/EBP-alpha (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-alpha. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULT(S): Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSION(S): MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-alpha and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

CCC publication: Will GRECCAR 2 be a Game Changer for the Management of Rectal Cancer?

Citation: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2020, 22(12), 2330

Author: Sun Myint A.; Sripadam R.; Dhadda A.; Rao C.; Pierre Gerard J.

Abstract: We read with interest the 5-year oncological outcomes for GRECCAR 2, including 

local recurrence, metastatic disease, and survival. 1 GRECCAR 2 is the first 

multicentre, randomised trial to compare local excision with total mesorectal 

excision (TME) in downstaged low rectal cancer. The oncological outcomes are 

comparable in both arms, suggesting that patients with cT2cT3 tumours can be 

offered local excision instead of TME surgery. This has major implications in 

the way we consent patients with rectal cancer. More importantly, could this be 

a game changer in rectal cancer management?

CCC publication: Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis

Citation: Clinical and Experimental Immunology. 2020, 202(3), 335-52
Author: Sasson S.C. (sarah.sasson@ndm.ox.ac.uk); Cheung V.T.F.; Gupta T.; Klenerman P.; Brain O.; Zaunders J.J.; Kelleher A.D.; Nahar K.; Scolyer R.A.; Carlino M.S.; Long G.V.; Menzies A.M.; Munier C.M.L.; Fairfax B.P.; Payne M.J.; Olsson-Brown A.; Jolly C.; Read S.A.; Ahlenstiel G.; Palendira U.

Abstract: The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers by flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC but not IN-C was associated with a high proportion of regulatory T cells (Treg). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint-inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients, compared with IN-NAE in one of two cohorts. UC but not IN-COL was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterised by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg, reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis (Figure1). 

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CCC publication: Peer support to maintain psychological wellbeing in people with advanced cancer: findings from a feasibility study for a randomised controlled trial

Citation: BMC Palliative Care. 2020, 19(1)
Author: Walshe; Roberts, Diane; Calman, Lynn; Appleton, Lynda; Croft, Robert; Skevington, Suzanne; Lloyd-Williams, Mari; Grande, Gunn; Perez Algorta, Guillermo
Abstract: Background

Advanced cancer affects people’s lives, often causing stress, anxiety and depression. Peer mentor interventions are used to address psychosocial concerns, but their outcomes and effect are not known. Our objective was to determine the feasibility of delivering and investigating a novel peer mentor intervention to promote and maintain psychological wellbeing in people with advanced cancer.

Methods

A mixed methods design incorporating a two-armed controlled trial (random allocation ratio 1:1) of a proactive peer mentor intervention plus usual care, vs. usual care alone, and a qualitative process evaluation. Peer mentors were recruited, trained, and matched with people with advanced cancer. Quantitative data assessed quality of life, coping styles, depression, social support and use of healthcare and other supports. Qualitative interviews probed experiences of the study and intervention.

Results

Peer mentor training and numbers (n = 12) met feasibility targets. Patient participants (n = 12, from 181 eligible who received an information pack) were not recruited to feasibility targets. Those who entered the study demonstrated that intervention delivery and data collection were feasible. Outcome data must be treated with extreme caution due to small numbers, but indicate that the intervention may have a positive effect on quality of life.

Conclusions

Peer mentor interventions are worthy of further study and researchers can learn from these feasibility data in planning participant recruitment and data collection strategies. Pragmatic trials, where the effectiveness of an intervention is tested in real-world routine practice, may be most appropriate. Peer mentor interventions may have merit in enabling survivors with advanced cancer cope with their disease.

Trial Registration

The trial was prospectively registered 13.6.2016: ISRCTN10276684.

Keywords: Cancer, Peer support, Feasibility study, Palliative care

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CCC publication: Radiotherapy-specific interprofessional learning through simulation

Citation: Radiography. 2021, 27(1), 187-192. 2020, S1078-8174(20), 30140-1. Online ahead of print
Author: Ball B(1), Kirby M(2), Ketterer SJ(2), Mullen E(3), Howard L(3), Bridge P(2)
Abstract: Introduction: Interprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative. Method(s): Small groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the "Readiness for Interprofessional Learning Scale" measured impact and a Likert-style survey gathered feedback from participants. Result(s): The session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge. Conclusion(s): Although beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts. Implications for practice: Simulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.

CCC publication: Hypertension and cardiovascular risk factors when treating cancer patients: underrecognised and undertreated

Citation: Journal of Human Hypertension. 2020 Aug 12. Online ahead of print
Author: Essa H(1), Pettitt AR(2), Lip GYH(3)(4)

CCC publication: Advancing Roles of Healthcare Professionals in Palliative Radiotherapy

Citation: Clinical Oncology. 2020, 32(11), 753-757. Epub 2020 Aug 17.
Author: Fitzpatrick C(1), Javor J(2), Zywine C(2), Job M(3), Gram V(4)
Abstract: New methods of working in relation to the management of patients requiring palliative radiotherapy are being embraced in hospital departments around the world. Team members are expanding on their previously assigned scope of practice to take on duties that had previously only been assigned to a consultant clinical oncologist. Career frameworks such as the four-tier model have been built upon to identify the skills held by other healthcare professionals and show how they may be best placed to take on additional roles within a patient pathway. Experiences of four departments in different countries report their local experiences in using both therapeutic radiographers and nursing staff to undertake advanced and consultant-level practice in relation to the management of both palliative radiotherapy patients and their research work streams. Involvement of other healthcare professionals within the clinical or research pathway for the management of palliative radiotherapy patients can be achieved. Their involvement can support clinicians and help to ensure the safe and efficient management of patients requiring palliative radiotherapy.

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CCC publication: Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents

Citation: Blood Advances. 2020, 4(16), 3977-89

Author: Roeker LE(1), Dreger P(2), Brown JR(3), Lahoud OB(1), Eyre TA(4), Brander DM(5), Skarbnik A(6), Coombs CC(7), Kim HT(8), Davids M(3), Manchini ST(3), George G(9), Shah N(9), Voorhees TJ(7), Orchard KH(10), Walter HS(11), Arumainathan AK(12), Sitlinger A(5), Park JH(1), Geyer MB(1), Zelenetz AD(1), Sauter CS(1), Giralt SA(1), Perales MA(1), Mato AR(1).

Abstract: Although novel agents (NAs) have improved outcomes for patients with chronic 

lymphocytic leukemia (CLL), a subset will progress through all available NAs. 

Understanding outcomes for potentially curative modalities including allogeneic 

hematopoietic stem cell transplantation (alloHCT) following NA therapy is 

critical while devising treatment sequences aimed at long-term disease control. 

In this multicenter, retrospective cohort study, we examined 65 patients with 

CLL who underwent alloHCT following exposure to ≥1 NA, including baseline 

disease and transplant characteristics, treatment preceding alloHCT, transplant 

outcomes, treatment following alloHCT, and survival outcomes. Univariable and 

multivariable analyses evaluated associations between pre-alloHCT factors and 

progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), 

nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among 

patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV 

acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 

27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial 

remission, and transplant characteristics were not independently associated with 

PFS. Hematopoietic cell transplantation-specific comorbidity index independently 

predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs 

and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of 

therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease 

control strategy that overcomes adverse CLL characteristics. Prior NAs do not 

appear to impact the safety of alloHCT, and survival outcomes are similar 

regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA 

immediately preceding alloHCT. Decisions about proceeding to alloHCT should 

consider comorbidities and anticipated response to remaining therapeutic 

options.

CCC publication: Beam characterisation studies of the 62 MeV proton therapy beamline at the Clatterbridge Cancer Centre

Citation: Physica Medica. 2020, 77, 108-20

Author: Jacinta Yap, Javier Resta-López, Andrzej Kacperek, Roland Schnuerer, Simon Jolly, Stewart Boogert, Carsten Welsch,
Abstract: The Clatterbridge Cancer Centre (CCC) in the United Kingdom is the world's first hospital proton beam therapy facility, providing treatment for ocular cancers since 1989. A 62 MeV beam of protons is produced by a Scanditronix cyclotron and transported through a passive delivery system. In addition to the long history of clinical use, the facility supports a wide programme of experimental work and as such, an accurate and reliable simulation model of the treatment beamline is highly valuable. However, as the facility has seen several changes to the accelerator and beamline over the years, a comprehensive study of the CCC beam dynamics is needed to firstly examine the beam optics. An extensive analysis was required to overcome facility related constraints to determine fundamental beamline parameters and define an optical lattice written with the Methodical Accelerator Design (MAD-X) and the particle tracking Beam Delivery Simulation (BDSIM) code. An optimised case is presented and simulated results of the optical functions, beam distribution, losses and the transverse rms beam sizes along the beamline are discussed. Corresponding optical and beam information was used in TOPAS to simulate transverse beam profiles and compared to EBT3 film measurements. We provide an overview of the magnetic components, beam transport, cyclotron, beam and treatment related parameters necessary for the development of a present day optical model of the facility. This work represents the first comprehensive study of the CCC facility to date, as a basis to determine input beam parameters to accurately simulate and completely characterise the beamline. Copyright © 2020 Associazione Italiana di

CCC publication: Adjuvant management of locally advanced oral squamous cell carcinoma – real world challenges and opportunities

Citation: British Journal of Oral and Maxillofacial Surgery. 2020
Author: R.C. Brooker, A. Hobkirk, H. Cashman, T. Sato, D. Broderick, H. Wong, P. Kyzas, A. Haridass, J.J. Sacco, A.G. Schache,

CCC publication: Artificial intelligence and soft skills in radiation oncology: Data versus wisdom

Citation: Journal of Medical Imaging and Radiation Sciences. 2020, 51(4). Online ahead of print
Author: Ian S. Boon, Jean S. Lim, Moi H. Yap, Tracy P.T. Au Yong, Cheng S. Boon,
Abstract: Background Patients with locally advanced oral squamous cell cancer (LAOSCC) are treated with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT), following surgical ablation. This depends on pathological risk factors and aims to reduce local recurrence risk and improve survival. Delivery of these aggressive treatments is however challenging particularly following major surgery.

Aim Describe real world delivery of multimodality treatment in LAOSCC, in a UK population with high levels of disease incidence and low socioeconomic status, informing adaptations necessary to deliver gold standard therapy.

Method Patients with LAOSCC (T1-4 N1-3/T3-4 N0) treated between October 2014–October 2016 with a minimum 24 months follow-up were included. Patients were identified using Somerset Cancer Register and data collected through retrospective case note review. Approval was obtained from relevant NHS institution audit departments and data analysed using IBM SPSS Statistics 24.

Results Analysis included 129 patients with 82% having initial performance status (PS) of 0-1. The most frequent PS change was 1 point drop (46%). 20 out of 93 patients eligible (22%) underwent adjuvant CRT. 40% (37) began adjuvant CRT/RT within 42 days and 85% (79) within 56 days. Delay in initiating adjuvant therapy was associated with higher rates of complication and longer post-operative hospital stay. Concordance between imaging and pathological nodal staging was poor (cK 0.223).

Conclusion PS frequently declines after complex surgical procedures and long post-operative recovery periods leading to difficulties providing adjuvant treatments within the national guidance of 42 days. Frequent deviation from planned adjuvant therapies highlights the need for improved treatment strategies.

Keywords: Oral cancer; squamous cell carcinoma; chemoradiotherapy; maxillofacial surgery; adjuvant

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CCC publication: The NICO Phase II clinical trial – Focus on an emerging immunotherapy strategy for the adjuvant treatment of locally advanced oral cancers

Citation: British Journal of Oral and Maxillofacial Surgery. 2020
Author: R.C. Brooker, A.G. Schache, J.J. Sacco,
Abstract: Outcomes remain poor for patients presenting with locally advanced oral cancers and it remains imperative to re-evaluate adjuvant therapies in order to provide individuals with improved outcomes, ideally without compromising on long term quality of life. We present current available evidence supporting the use of immune checkpoint inhibitors (ICI) in squamous cell carcinoma of the head and neck (SCCHN) and discuss trials examining the integration of ICI into the locoregional management of resectable SCCHN. We focus particularly on the NICO trial which is investigating the integration of neoadjuvant and adjuvant ICI into the treatment of resectable locally advanced oral cavity cancers.

Keywords: Oral Cancer; squamous cell cancer; immune checkpoint inhibitors; immunotherapy; chemoradiotherapy; adjuvant

CCC publication: COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Citation: The Lancet. Oncology. 2020, 21(10), 1309-1316. Epub 2020 Aug 24
Author: Lennard Y W Lee, Jean-Baptiste Cazier, Thomas Starkey, Sarah E W Briggs, Roland Arnold, Vartika Bisht, Stephen Booth, Naomi A Campton, Vinton W T Cheng, Graham Collins, Helen M Curley, Philip Earwaker, Matthew W Fittall, Spyridon Gennatas, Anshita Goel, Simon Hartley, Daniel J Hughes, David Kerr, Alvin J X Lee, Rebecca J Lee, Siow Ming Lee, Hayley Mckenzie, Chris P Middleton, Nirupa Murugaesu, Tom Newsom-Davis, Anna C Olsson-Brown, Claire Palles, Thomas Powles, Emily A Protheroe, Karin Purshouse, Archana Sharma-Oates, Shivan Sivakumar, Ashley J Smith, Oliver Topping, Chris D Turnbull, Csilla Várnai, Adam D M Briggs, Gary Middleton, Rachel Kerr, Abigail Gault, Michael Agnieszka, Ahmed Bedair, Aisha Ghaus, Akinfemi Akingboye, Alec Maynard, Alexander Pawsey, Ali Abdulnabi Mohamed, Alicia Okines, Alison Massey, Amy Kwan, Ana Ferreira, Angelos Angelakas, Anjui Wu, Ann Tivey, Anne Armstrong, Annet Madhan, Annet Pillai, Ashley Poon-King, Bartlomiej Kurec, Caroline Usborne, Caroline Dobeson, Christina Thirlwell, Christian Mitchell, Christopher Sng, Christopher Scrase, Christopher Jingree, Clair Brunner, Claire Fuller, Clare Griffin, Craig Barrington, Daniel Muller, Diego Ottaviani, Duncan Gilbert, Eliana Tacconi, Ellen Copson, Emily Renninson, Emma Cattell, Emma Burke, Fiona Smith, Francesca Holt, Gehan Soosaipillai, Hayley Boyce, Heather Shaw, Helen Hollis, Helen Bowyer, Iris Anil, Jack Illingworth, Jack Gibson, Jaishree Bhosle, James Best, Jane Barrett, Jillian Noble, Joseph Sacco, Joseph Chacko, Julia Chackathayil, Kathryn Banfill, Laura Feeney, Laura Horsley, Lauren Cammaert, Leena Mukherjee, Leonie Eastlake, Louise Devereaux, Lucinda Melcher, Lucy Cook, Mabel Teng, Madeleine Hewish, Madhumita Bhattacharyya, Mahbuba Choudhury, Mark Baxter, Martin Scott-Brown, Matthew Fittall, Michael Tilby, Michael Rowe, Michael Agnieszka, Mohammed Alihilali, Myria Galazi, Nadia Yousaf, Neha Chopra, Nicola Cox, Olivia Chan, Omar Sheikh, Paul Ramage, Paul Greaves, Pauline Leonard, Peter S Hall, Piangfan Naksukpaiboon, Pippa Corrie, Rahul Peck, Rachel Sharkey, Rachel Bolton, Rebecca Sargent, Rema Jyothirmayi, Robert Goldstein, Roderick Oakes, Rohan Shotton, Ruhi Kanani, Ruth Board, Ruth Pettengell, Ryan Claydon, Sam Moody, Samah Massalha, Sangary Kathirgamakarthigeyan, Saoirse Dolly, Sarah Derby, Sarah Lowndes, Sarah Benafif, Sarah Eeckelaers, Sarah Kingdon, Sarah Ayers, Sean Brown, Shawn Ellis, Shefali Parikh, Sian Pugh, Simon Shamas, Simon Wyatt, Simon Grumett, Sin Lau, Yien Ning Sophia Wong, Sophie McGrath, Stephanie Cornthwaite, Stephen Hibbs, Tania Tillet, Taslima Rabbi, Tim Robinson, Tom Roques, Vasileios Angelis, Victoria Woodcock, Victoria Brown, YingYing Peng, Yvette Drew, Zoe Hudson,
Abstract: BackgroundPatients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK.
Methods. We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case–fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models.
Findings 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case–fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40–49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15–2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case–fatality rate (2·25, 1·13–4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09–4·08; p=0·028).
Interpretation Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk–benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies.
Funding University of Birmingham and University of Oxford.

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WUTH publication: Primary tuberculosis of the fibular diaphysis: A rare case report

Citation: International Journal of Surgery Case Reports. 2020, 74, 140-3
Author: Garg SK, Singhal A, Malhotra A
Abstract: Introduction: Primary diaphyseal tuberculosis has very low occurrence. With no systemic signs and specific radiographic features, there exists low index of suspicion, which may delay the diagnosis of tuberculosis.
Presentation of case: A female aged 15 years presented with chronic leg pain and swelling for past 7 months. There was no significant history of tuberculosis present. On investigations ESR was 44 mm and positive mantoux test. Chest radiograph was normal. On x-ray (R) fibula intramedullary eccentric lytic lesion and on MRI (R) leg intramedullary lytic lesion was present suggestive of ewing's sarcoma. On histopathology epitheloid granulomas with langhans giant cells were present. Category 1 antitubercular drug regimen was started and lesion healed with alleviations of signs & symptoms.
Discussion: Tuberculosis presents with typical signs and symptoms in adults compared with children in whom cystic tubercular lesions in shaft of long bones presents mostly as a single solitary intramedullary lytic lesion on MRI, which corresponds with other more common differentials. This clinical and radiological heterogeneity warrants lesional biopsy and culture to determine the right diagnosis to aid in early starting of correct treatment and recovery of the patient.
Conclusion: With atypical presentation of diaphyseal tuberculosis in children, a high index of suspicion with unexplained pain and swelling of the bone could help to establish the diagnosis.
Keywords: Case report; Diaphysis; Ewings sarcoma; Fibula; Tuberculosis.

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WUTH publication: Comment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis

Citation: Rheumatology. 2020, 59(12), e159. [2020 Aug 23. Online ahead of print]
Author: Oparaji BU, Clearkin L, Ferson S, De Angelis M, Ferrer-Fernandez M, Calleja D, Gray N, Derrer-Merk E

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WUTH publication: Application of artificial intelligence (AI) in Radiotherapy workflow: Paradigm shift in Precision Radiotherapy using Machine Learning

Citation: The British Journal of Radiology. 2019, 92(1103), 20190716

Author: Boon IS, Au Yong TPT, Boon CS

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WUTH publication: Recalcitrant Foot Ulceration in a Patient With Type 1 Diabetes Mellitus

Citation: Cureus. 2020, 12(6), e8898

Author: Vazeille S, Hawker L, Chandrasekar R, Srinivas-Shankar U

Abstract: We describe the case of a middle-aged woman with type 1 diabetes mellitus who presented to the emergency department with diabetic ketoacidosis. An intravenous cannula was inserted into the veins of the dorsum of the right foot due to difficulty in obtaining intravenous access in the upper limb for managing diabetic ketoacidosis. Our patient developed edema and bullae on the dorsum of the right foot and received intravenous antibiotics for bullous cellulitis. Our patient developed ulceration on the dorsum of the right foot and over the next few months was admitted to hospital on several occasions with infected foot ulceration, which required several courses of intravenous antibiotics, larval therapy and surgical debridement of the necrotic eschar and slough. With regular review in the multidisciplinary diabetic foot clinic, the foot ulceration finally healed in eight months. This case highlights the importance of avoiding trauma in any form to the feet of people with diabetes even if aseptic techniques are taken.
Keywords: cannula; critical care; delayed wound healing; diabetic foot ulcers management; diabetic ketoacidosis; larval therapy; surgical debridement; type i diabetes mellitus.

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