CCC publication: 611O Abiraterone acetate plus prednisolone for hormone-naïve prostate cancer (PCa): Long-term results from metastatic (M1) patients in the STAMPEDE randomised trial (NCT00268476),

Citation: Annals of Oncology. 2020, 31(Sup4), S509

Author: N. James, H. Rush, N. Clarke, G. Attard, A. Cook, D. Dearnaley, S. Gillessen, A. Hoyle, R. Jones, R. Millman, A. Birtle, S. Chowdhury, J. Gale, Z. Malik, J. O'Sullivan, C. Pezaro, D. Sheehan, J. Tanguay, M.K. Parmar, M.R. Sydes,

CCC publication: PIVOTALboost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost (CRUK/16/018)

Citation: Clinical and Translational Radiation Oncology. 2020, 25, 22-8

Author: Isabel Syndikus, Clare Cruickshank, John Staffurth, Alison Tree, Ann Henry, Olivia Naismith, Helen Mayles, Nicola Snelson, Shama Hassan, Stephanie Brown, Nuria Porta, Clare Griffin, Emma Hall,

WUTH publication: Non-anaemic iron deficiency should be investigated with the same priority as iron deficiency anaemia in fast track colorectal clinics-retrospective cohort study

Citation: Journal of Gastrointestinal oncology. 2020, 11(4), 609-615 

Author: Majeed T, Solomon J, Ali RS, Chitsabesan P

Abstract: Background:  Since year 2000 the diagnostic criterion for fast track (FT) referrals for patients with suspected colorectal cancer (CRC) is used in the UK. Iron deficiency anaemia (IDA) is one of the diagnostic criteria. There is a strong evidence in the literature which suggests that Iron deficiency (ID) alone has a strong relationship with CRC. Non-anaemic Iron deficiency (NAID) and all other types of anaemia are investigated outside the scope of FT clinics. We postulated that patients with ID regardless of degree of anaemia have an increased risk of CRC. By confirming this hypothesis, we can broaden the scope of the diagnostic criterion for referral that can help to increase diagnostic yield of FT CRC services. 

Methods:  A retrospective observational cohort study was conducted from a dedicated data for FT clinics from 2016-2018. Association between CRC and different forms of anaemia, Iron deficiency alone and bowel symptoms was determined. 

Results:  Patients with iron deficiency (low MCV, MCH and ferritin) regardless of degree of anaemia were found more likely to have CRC. Factors like age, gender, family history and bowel symptoms (except abdominal mass) showed a very weak association with CRC in patients with ID. 

Conclusions:  ID without anaemia has a strong relationship with CRC and should be investigated with the same priority as IDA is investigated. 

Keywords:  Iron deficiency anaemia; colorectal cancer (CRC); colorectal surgery; department of health diagnostic criterion; fast track clinics; iron deficiency; iron deficiency without anaemia; two weeks wait.

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WUTH publication: Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti-TNF-refractory Crohn's disease

Citation: Alimentary pharmacology and therapeutics. 2020, 52(8), 1341-52
Author: Townsend T, Razanskaite V, Dodd S, Storey D, Michail S, Morgan J, Davies M, Penman D, Watters C, Swaminathan M, Sabine J, Chapman A, Smith PJ, Flanagan PK, Reilly I, Bodger K, Subramanian S
Abstract: Background:  Anti-tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting.
Aim:  To compare the effectiveness of ustekinumab and vedolizumab in anti-TNF-refractory Crohn's disease over 12 months.
Methods:  Patients commencing ustekinumab or vedolizumab for anti-TNF-refractory Crohn's disease with minimum follow-up of 12 months were included. The primary outcome measure was the difference in steroid-free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid-free remission and clinical response and remission.
Results:  We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid-free and clinical remission were significantly higher among ustekinumab-treated patients. After adjusting for confounders, steroid-free remission was higher among ustekinumab-treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06-7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89-4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007).
Conclusions:  Ustekinumab appeared more effective in treating anti-TNF-refractory Crohn's disease and more patients persisted with therapy. 

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WUTH publication: Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score

Citation: BMC Geriatrics. 2020, 20(1), 346

Author: Danjuma MI, Almasri H, Alshokri S, Khir FK, Elmalik A, Battikh NG, Abdallah IMH, Elshafei M, Fatima H, Mohamed MFH, Maghoub Y, Hussain T, Kamal I, Anwer Z, Bidmos MA, Elzouki AN

Abstract: Background: Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI.

Methods: We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes.

Results: The cases examined for the determination of DILI avoidability had probability likelihood of "probable" or "highly probable" by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as "avoidable" ("probable" or "definite") by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf's kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively.

Conclusion: We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

Keywords: Avoidability; preventability; DILI; LAAT; elderly patients.

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WUTH publication: The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development

Citation: Mediators of Inflammation. 2020 Aug 31;2020:7418342. eCollection 2020.

Author: Cheng Z, Abrams ST, Austin J, Toh J, Wang SS, Wang Z, Yu Q, Yu W, Toh CH, Wang G

Abstract: The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-κB pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.

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WUTH publication: An audit of process and outcome for emergency colectomy in England and Wales

Citation: Colorectal Disease. 2020 Sep 16. Online ahead of print.

Author: Burns EM, Poulton T, Deputy M, Pinkney T, Guy R

Abstract: Aim: To describe process and outcome for patients undergoing emergency colectomy for colitis in England and Wales.

Methods: National Emergency Laparotomy Audit (NELA) is a national audit including patients undergoing emergency laparotomy and laparoscopic resectional procedures. Adult patients under 65 years oldwho underwent emergency subtotal colectomy or panproctocolectomy for colitis between 2013-2016 were analysed.

Results: In total 1204 patients were included. Although approximately a third of patients underwent a colectomy within five days of admission [37% (440/1204)], 32% (383/1204) were admitted for more than ten days prior to surgery. Colorectal surgeons were present at operation in 72% (869/1204) of cases and consultant surgeons attended 94%(1137/1204) of procedures.Laparoscopy was attempted in 32%(390/1204) of operations with wide institutional variation in its use (0-100% of cases). The overall 30-day inpatient mortality was 2.9%(35/1204). On multivariableregression analysis, age>55 [odds ratio(OR) 3.59(1.05-12.21), p=0.041], female gender [OR 2.88(1.27-6.52), p=0.011], and ASA of 5 [OR 37.43 (2.72-514.52), p=0.007] were associated with increased mortality.

Conclusion: There is a consultant-driven service that is largely delivered by specialist Colorectal surgeons. Laparoscopy rates were high although there was wide variation in use across institutions. Preoperative delays were evident and further work is necessary to determine the underlying reasons forthese.

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WUTH publication: Tax-otsubo': stress cardiomyopathy following an encounter with the Inland Revenue

Citation: BMJ Case Reports. 2020, 13(1), e232225
Author: Roach MW, Currie P
Abstract: An 89-year-old man developed chest pain and palpitations shortly after finishing a stressful 40 min phone call to HM Revenue and Customs. After admission to the emergency department, he had a cardiovascular collapse followed soon after by a cardiac arrest due to ventricular fibrillation (VF). The troponin T was elevated and his ECG showed extensive deep T wave inversion with prolongation of the QT interval. A portable hand-held ultrasound device (VScan; GE Healthcare) was used to demonstrate classical apical ballooning of the left ventricular apex indicating a diagnosis of takotsubo stress cardiomyopathy. Shortly following admission to the cardiac care unit, he had a further episode of VF, which was successfully defibrillated. A coronary angiogram was performed, which was normal. He was treated with a short course of benzodiazepines. He was discharged after 8 days without any neurological deficit. His echocardiogram subsequently showed complete resolution of the abnormalities of the left ventricular function.

Keywords: arrhythmias; clinical diagnostic tests; heart failure.

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WUTH publication: Reply to "Fluoroscopy during coccygectomy for rectal cancer"

Citation: Techniques in colproctology. 2020 Aug 29 Online ahead of print
Author: Simpson G, Marks T, Blacker S, Smith D, Walsh C

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WUTH publication: Legacy of COVID-19 - the opportunity to enhance surgical services for patients with colorectal disease

Citation: Colorectal Disease. 2020 Aug 28. Online ahead of print
Author: Arulampalam T, Bhangu A, Brown SR, Clark SK, Din F, Harji D, Knowles CH, McNamara D, Moug SJ, Smart N, Tierney G, Torkington J, Walsh C, Watson A, Fearnhead NS
Abstract: The COVID-19 crisis has undoubtedly taken a toll on the care of patients with colorectal disease. Elective services, be that face to face contact, endoscopy or operating all but ceased during the pandemic.

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