Citation: Cureus. 2021, 13(12), e20382. eCollection 2021 Dec.
Author: Mohamed A Salman, Ahmed Safina, Ahmed Salman, Mohamed Farah, Khaled Noureldin, Mohamed Issa, Ahmed Dorra, Mohamed Tourky, Hossam El-Din Shaaban, Mohammed Aradaib
Abstract: Purpose We aimed to investigate the impact of reinforcement and abdominal drains on the outcome of laparoscopic sleeve gastrectomy (LSG). Methods The present study was a prospective study that included obese patients scheduled to undergo LSG. Patients were assigned to receive drain, reinforcement, or both according to the surgeon's preference and followed up for one month after surgery. The present study's primary outcome was the identification of the association between intraoperative drain/reinforcement and the incidence of postoperative complications. Results A total of 125 (20.3%) patients received intraoperative drains. The proportion of postoperative morbidity was comparable between the drain and non-drain groups (3.2% versus 1.6%; p = 0.25). Patients in the drain group had similar incidence of blood transfusion (2.4% versus 1.7% in non-drain group; p = 0.43) and postoperative leakage (0.8% versus 0.2% in non-drain group; p = 0.36). The incidences of blood transfusion (p = 0.56) and reoperation (p = 0.98) were comparable between the drain and non-drain groups. There were no statistically significant differences between the drain and non-drain groups regarding postoperative mortality and wound infection (p > 0.05). On the other hand, 440 (71.3%) patients received reinforcement. The proportion of postoperative morbidity was comparable between the reinforcement and non-reinforcement groups (1.6% versus 2.8%, p = 0.07). Patients in the reinforcement group were less likely to develop postoperative bleeding (0.7% versus 4% in the non-reinforcement group; p = 0.004), while no significant difference was detected in terms of postoperative leakage (p = 0.33) and in-hospital mortality. Conclusion In conclusion, abdominal drainage did not reduce the complications of LSG patients. Reinforcement has some role in controlling the bleeding but not leaks. Both techniques did not significantly impact the mortality rate. In the future, additional, large randomized trials are needed to examine the gastrointestinal-related quality of life.
Keywords: bariatric; bariatric surgery; complications; drain; reinforcement; surgery.
Thursday, 23 December 2021
WUTH publication: The Impact of Drain and Reinforcement on the Outcomes of Bariatric Surgery: A Prospective Study
WUTH publication: A Systematic Review Examining the Experimental Methodology Behind In Vivo Testing of Hiatus Hernia and Diaphragmatic Hernia Mesh
Citation: Journal of Gastrointestinal Surgery. 2021 Dec 21. Online ahead of print
Author: Thomas Whitehead-Clarke, Victoria Beynon, Jessica Banks, Rustam Karanjia, Vivek Mudera, Alastair Windsor, Alvena Kureshi
Abstract: Introduction: Mesh implants are regularly used to help repair both hiatus hernias (HH) and diaphragmatic hernias (DH). In vivo studies are used to test not only mesh safety, but increasingly comparative efficacy. Our work examines the field of in vivo mesh testing for HH and DH models to establish current practices and standards.
Method: This systematic review was registered with PROSPERO. Medline and Embase databases were searched for relevant in vivo studies. Forty-four articles were identified and underwent abstract review, where 22 were excluded. Four further studies were excluded after full-text review-leaving 18 to undergo data extraction.
Results: Of 18 studies identified, 9 used an in vivo HH model and 9 a DH model. Five studies undertook mechanical testing on tissue samples-all uniaxial in nature. Testing strip widths ranged from 1-20 mm (median 3 mm). Testing speeds varied from 1.5-60 mm/minute. Upon histology, the most commonly assessed structural and cellular factors were neovascularisation and macrophages respectively (n = 9 each). Structural analysis was mostly qualitative, where cellular analysis was equally likely to be quantitative. Eleven studies assessed adhesion formation, of which 8 used one of four scoring systems. Eight studies measured mesh shrinkage.
Discussion: In vivo studies assessing mesh for HH and DH repair are uncommon. Within this relatively young field, we encourage surgical and materials testing institutions to discuss its standardisation. Keywords: Hernia; Hiatus; In vivo; Mesh; Testing.
Thursday, 16 December 2021
WUTH publication: Re: Clinical evaluation of a deep-learning-based computer-aided detection system for the detection of pulmonary nodules in a large teaching hospital
Author: I S Boon, R P J Teo, M H Yap, J S Lim, H L Goh, C S Boon, T P T Au Yong
Wednesday, 8 December 2021
WUTH publication: Advances of Cancer Genomics in Oncology Care
Citation: Clinical Oncology. 2021, S0936-6555(21), 00432-5. Online ahead of print
Author: I S Boon, J Tan, R P J Teo, T P T Au Yong, C S Boon
Tuesday, 30 November 2021
WUTH publication: Continuous glucose monitoring systems for monitoring cystic fibrosis-related diabetes
Author: Aileen Toner, Anna McCloy, Paula Dyce, Dilip Nazareth, Freddy Frost
Abstract: Background: Cystic fibrosis (CF) is one of the most common life-shortening autosomal-recessive genetic conditions with around 100,000 people affected globally. CF mainly affects the respiratory system, but cystic fibrosis-related diabetes (CFRD) is a common extrapulmonary co-morbidity and causes excess morbidity and mortality in this population. Continuous glucose monitoring systems (CGMS) are a relatively new technology and, as yet, the impact of these on the monitoring and subsequent management of CFRD remains undetermined.
Monday, 29 November 2021
WUTH publication: Acute critical care course for interns to develop competence
Citation: The National Medical Journal of India. 2021, 34(3), 167-70
Author: Navdeep Sokhal, Akshay Kumar, Richa Aggarwal, Keshav Goyal, Kapil Dev Soni, Rakesh Garg, Ashok Deorari, Ajay Sharma
Abstract: Background All medical graduates must know how to stabilize and manage critically ill patients. A 2-day intensive course, called the acute critical care course (ACCC), was conducted to train interns in technical and non-technical skills for managing a patient whose condition is deteriorating. This analysis aims to assess the feasibility and effectiveness of ACCC for interns. Methods We developed and conducted the ACCC to train interns. It included lectures and skill stations. Twenty-four interns participated in the course. Immediate, post-course, quantitative and qualitative feedback was taken online. Qualitative information was also collected verbally and later by email. These data were analysed both quantitatively and qualitatively. Thematic analysis was used to identify, analyse and report the patterns of responses and behaviour. Results The average score for the utility of the course was 4.7 and for the skill stations it was 4.6 on a scale of 5. The qualitative analysis of the feedback emphasized the need for the course before the clinical posting and more skill-based modules rather than lectures. The interactive style of teaching and training in communication using role-play was appreciated. Few suggestions to improve the course were provided. Conclusions Implementing the ACCC needed simulation, interactive discussions, role-play, modified Pendleton's feedback, and reflective exercise that form the basis of a range of educational principles. The blended learning set of objectives of ACCC were the pillars for this successful internship training programme.
Friday, 26 November 2021
WUTH publication: Epistaxis in people with hereditary haemorrhagic telangiectasia: surgical management and psychological impact
Citation: British Journal of Hospital Medicine. 2021, 82(11), 1-10
Author: H A Crouch-Smith, K J Fenn, S P Williams
Abstract: From the emergency management of acute epistaxis to the surgical procedures for chronic epistaxis, this article covers the options available to control the archetypal symptom of hereditary haemorrhagic telangiectasia while exploring the psychological effect such a disease has on the patient.
Keywords: Epistaxis; Genetics; Psychology; Surgery.
Friday, 12 November 2021
WUTH publication: SARS-CoV-2 infection is associated with an increased risk of idiopathic acute pancreatitis but not pancreatic exocrine insufficiency or diabetes: long-term results of the COVIDPAN study
Citation: Gut. 2021 Nov 11. Online ahead of print.
Author: Manu Nayar, Chris Varghese, Aditya Kanwar, Ajith K Siriwardena, Ali Raza Haque, Altaf Awan, Anita Balakrishnan, Arab Rawashdeh, Bogdan Ivanov, Chetan Parmar, Christopher M Halloran, Clifford Caruana, Cynthia-Michelle Borg, Dhanny Gomez, Dimitrios Damaskos, Dimitrios Karavias, Guy Finch, Husam Ebied, James K Pine, James R A Skipworth, James Milburn, Javed Latif, Jeyakumar Apollos, Jihène El Kafsi, John A Windsor, Keith Roberts, Kelvin Wang, Krish Ravi, Maria V Coats, Marianne Hollyman, Mary Phillips, Michael Okocha, Michael Sj Wilson, Nadeem A Ameer, Nagappan Kumar, Nehal Shah, Pierfrancesco Lapolla, Connor Magee, Bilal Al-Sarireh, Raimundas Lunevicius, Rami Benhmida, Rishi Singhal, Srinivasan Balachandra, Semra Demirli Atıcı, Shameen Jaunoo, Simon Dwerryhouse, Tamsin Boyce, Vasileios Charalampakis, Venkat Kanakala, Zaigham Abbas, Nilanjana Tewari, Sanjay Pandanaboyana, COVID Pain Collborative Group
Abstract: Keywords: COVID-19; acute pancreatitis; pancreas.
Thursday, 11 November 2021
WUTH publication: The Role of Indocyanine Green Fluorescence Angiography in Complex Abdominal Wall Reconstruction: A Scoping Review of the Literature
Citation: Journal of plastic, reconstrucitve & aesthetic surgery. 2021 Oct 8, S1748-6815(21), 00435-6. Online ahead of print
Author: Simon T Adams, Christian West, Ciaran J Walsh
Abstract: Background: Indocyanine green fluorescence angiography (ICGFA) is a technique for assessing vascularity and perfusion which has multiple proven applications across a variety of surgical procedures. Studies have been performed assessing its potential role in evaluating skin flap viability in complex abdominal wall reconstruction (CAWR) in order to avoid postoperative surgical site occurrences (SSO).
Objectives: This scoping review was intended to summarise the literature concerning ICGFA in CAWR in order to facilitate future evidence-based guidelines for its use.
Eligibility criteria: Inclusion - cohort studies, randomised controlled trials, case series, case reports and ventral midline hernias only. Exclusion - patients aged under 18 years and non-human test subjects.
Sources of evidence: PubMed, MEDLINE®, Cochrane, Embase and OpenGrey
RESULTS: A total of 3416 unique titles were yielded from our search of which 9 met our inclusion criteria: 3 case reports, 1 retrospective case series, 1 prospective case series, 3 non-blinded, non-randomised retrospective case-controlled studies and 1 prospective, double-blinded randomised controlled study. The included studies varied considerably in size and method however the consensus appeared to support ICGFA as being a safe and feasible means of assessing tissue flap vascularity in CAWR. The studies returned contrasting results regarding the impact of ICGFA in predicting and avoiding SSOs however there were insufficient numbers of studies for a meta-analysis.
Conclusions: We identify three case reports and four lower quality studies suggesting a possible application for ICGFA in CAWR and two higher quality studies showing no overall benefit. Evidence-based guidelines on the role of ICGFA in CAWR will require the assessment of further studies.
Keywords: Abdominal wall reconstruction; Fluorescence angiography; Hernia; ICG; Indocyanine green.
Tuesday, 9 November 2021
WUTH publication: Phenotypic spectrum of serious cutaneous only adverse event following immunisation with COVID-19 vaccines: a multi-centre case series and literature review
Citation: Clinical and experimental dermatology. 2021 Nov 8. Online ahead of print.
Author: M Balogun, D Millette, V Yip, S A Chan, P Lee, N Gamal, N Hashim, D Phillips, M Walsh, P Trehan, L Hanna-Bashara, A Abdullah, A Wernham, S Tso
Abstract: A phenotypic plethora of exclusively cutaneous adverse events following immunisation (AEFI) with COVID-19 vaccines have been described. Currently, there is no formal consensus on advice given to affected individuals, pertaining to their subsequent COVID-19 vaccines, which is increasingly pertinent as countries such as the United Kingdom launch a further booster phase of the COVID-19 mass vaccination program due to concerns over waning immunity from initial vaccinations.
Thursday, 4 November 2021
WUTH publication: Patient-Centred Digital Medicine
Citation: Clinical Oncology. 2021 Oct 31
Author: J S Lim, H L Goh, T P T Au Yong, C S Boon, I S Boon
Tuesday, 26 October 2021
WUTH publication: CNS infection with a history of recurrent epistaxis: Streptococcal meningitis as a first presentation of juvenile nasopharyngeal angiofibroma
Citation: Acute Medicine. 2021, 20(3), 231-33
Author: S Biart, M Shakeshaft, K Joseph
Abstract: An adolescent male with a history of recurrent epistaxis presented with headache and vomiting. Investigations revealed concurrent meningitis as well as the presence of a subarachnoid haemorrhage. Subsequent imaging identified a Juvenile Nasopharyngeal Angiofibroma; a rare but important cause of meningitis that should be considered in the young adult population.
WUTH publication: Focused Acute Medicine Ultrasound (FAMUS): uptake, completion and barriers to accreditation after two years
Author: J Russell, M Dachsel, A Gilmore, R Matsa, N Smallwood
Abstract: The Society for Acute Medicine launched their ultrasound accreditation in September 2016, involving a practical course alongside completion of scanning competencies. Candidates require a registered supervisor to oversee their training. We present here the results of a survey of attendees of practical courses approximately 2 years after launch. The majority of respondents were Consultants or trainees within AIM. Fourteen of 76 (18.4%) respondents had completed the whole accreditation process, whilst 51 (67.1%) had not completed any of the three individual modules. The biggest barriers to accreditation were seen to be lack of supervisors, and lack of dedicated training time. There was good uptake of available online learning resources with good feedback. These results will be used to help develop the training pathway further and widen access to ultrasound training within the specialty and beyond.
Tuesday, 19 October 2021
WUTH publication: Assessment of anti-factor Xa activity in critically ill COVID-19 patients receiving three different anticoagulation regimens
Citation: SAGE open medicine. 2021 Oct 11, 9, 20503121211049931. eCollection 2021
Author: Mohammed A Hamad, Shereen A Dasuqi, Aamer Aleem, Rasha A Omran, Rakan M AlQahtani, Fahad A Alhammad, Abdulaziz H Alzeer
Abstract: Introduction: Critically ill COVID-19 patients are at increased risk of thrombosis with an enhanced risk of bleeding. We aimed to explore the role of anti-factor Xa levels in optimizing the high-intensity anticoagulation's safety and efficacy and finding possible associations between D-dimer levels, cytokine storm markers, and COVID-19-induced coagulopathy or thrombophilia.
Methods: Retrospective cohort study conducted on 69 critically ill COVID-19 patients who received three regimens of higher intensity anticoagulation.
Results: Seventeen patients (24.6%) received high-dose enoxaparin prophylaxis, 29 patients (42%) received therapeutic doses of enoxaparin, and 23 patients (33.3%) were on therapeutic unfractionated heparin infusion. Fewer than one-third of the whole cohort (n = 22; 31.8%) achieved the target range of anti-factor Xa. The patients were divided into three subgroups based on anti-factor Xa target status within each anticoagulation regimen; when compared, the only association observed among them was for interleukin-6 levels, which were significantly higher in both the "above the expected range" and "below the expected range" groups compared with the "within the expected range" group (p = 0.009). Major bleeding episodes occurred in 14 (20.3%) patients and were non-significantly more frequent in the "below the expected anti-factor Xa range group" (p = 0.415). Seven patients (10.1%) developed thrombosis. The majority of patients had anti-factor Xa levels below the expected ranges (four patients, 57.1%).
Conclusion: Conventional anti-factor Xa ranges may not be appropriate as a predictive surrogate for bleeding in critically ill COVID-19. The clinical decision to initiate therapeutic anticoagulation preemptively may be individualized according to thrombosis and bleeding risks. Cytokine storm markers, namely, interleukin-6, may play a role in COVID-19-induced coagulopathy or thrombophilia.
Keywords: Anti-factor Xa; COVID-19; anticoagulation; bleeding; intensive care unit; thrombosis.
WUTH publication: An Unusual and Rare Metachronous Ipsilateral Ureteric Stump Metastasis Post Radical Nephrectomy
Citation: Cureus. 2021, 13(9), e17727. eCollection 2021 Sep
Author: Ramandeep Chalokia, Chinedum Anosike, Lee Robinson, Catherine Manson, Manal Kumar
Abstract: We report a case of recurrence of chromophobe renal cell cancer in the ipsilateral ureteric stump eight years later after the primary tumor was excised successfully. Before this detection of the recurrence, the patient had presented with recurrent episodes of hematuria four years after the radical nephrectomy was performed and the investigations were inconclusive. Eventually, the lesion was detected on flexible cystoscopy in the area of the right ureteric orifice protruding in the bladder. Transurethral resection of the tumor surprisingly revealed a chromophobe renal cancer with similar features seen in the primary tumor specimen. The patient underwent robotic-assisted laparoscopic excision of the ureteric stump with a cuff of the bladder and has been recurrence-free for five years on regular surveillance scans.
Keywords: chromophobe renal cell carcinoma; computed tomography; hematuria; metachronous; ureteric stump metastases.
Friday, 8 October 2021
WUTH publication: Religious Fasting of Muslim Patients After Metabolic and Bariatric Surgery: a Modified Delphi Consensus
Citation: Obesity Surgery. 2021 Oct 6. Online ahead of print
Author: Mohammad Kermansaravi, Islam Omar, Kamal Mahawar, Shahab Shahabi, Ahmad Bashir, Ashraf Haddad, Alaa Abbass, Syed Imran Abbas, Mujjahid Abbas, Tarek Abouzeid, Faki Akin, Ebrahim Aghajani, Ali Aminian, Mohanad AlAnsari, Syed Tanseer Asghar, Ahmet Ziya Balta, Waleed Bukhari, Mohamad Hayssam Elfawal, Waleed Gado, Khaled Gawdat, Tikfu Gee, Bijan Ghavami, Ramen Goel, Mohammed AlHadad, Bader AlHadhrami, Mohammad AlHaifi, Ali AlHamdani, Ibrahim Hassan, Selim Jalil Illan, Atif Inam, Aiman Ismaeil, Yasser Kayyal, Khaleel Mohammad, Amir Ulhagh Khan, Mousa Khoursheed, Haris Khwaja, K S Kular, Laurent Abram Layani, Maazulhassan, Tarek Mahdy, Mumtaz Maher, Ebrahim Mansoor, Salman Mirza, Muhammad S Niam, Taryel Omarov, Abdolreza Pazouki, Aayed R Alqahtani, Mohamed Qassem, Masoud Rezvani, Karim Sabry, Safauldeen Salim, Asim Shabbir, Mehdi Skalli, Osama Taha, Mohammad Talebpour, Halit Eren Taskin, Mustafa Taskin, Tahir Yunus, Amir Hossein Davarpanah Jazi, Radwan Kassir, Abdelrahman Nimeri
Abstract: Background: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS.
Methods: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus.
Results: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively.
Conclusion: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.
Keywords: Bariatric surgery; Calorie restriction; Consensus statement; Fasting; Metabolic surgery; Obesity; Ramadan.
Monday, 4 October 2021
WUTH publication: Communication skills training through 'role play' in an acute critical care course
Author: Akshay Kumar, Navdeep Sokhal, Richa Aggarwal, Keshav Goyal, Kapil Dev Soni, Rakesh Garg, Sanjeev Bhoi, Ashok Deorari, Ajay Sharma
Abstract: Background: . Effective patient-doctor communication is a key component of patient-centred care, which is one of the six pillars of quality healthcare delivery. Structured and effective communication skills training for healthcare providers is the need of hour in medical education. We assessed the efficacy of role play and simulation in developing communication skills.
Friday, 24 September 2021
WUTH publication: Is the use of augmented reality-assisted surgery beneficial in urological education? A systematic review
Citation: Current Urology. 2021, 15(3), 148-52. Epub 2021 Aug 17
Author: Ibraheem Alrishan Alzouebi, Sanad Saad, Tom Farmer, Sophie Green
Abstract: Background: Google Glass is an optical head-mounted display that has been used in multiple medical and surgical settings to enhance delivery of education and training. This systematic review focuses solely on the use of this technology in urology operating theaters for the purpose of surgical education.
Materials and methods: A systematic search strategy was employed using EMBASE (1996-2019), Medline (1946-2019) and PubMed. Search terms included optical head-mounted displays, Google Glass and urological surgical training. Use of this technology in a nonurological setting, nonteaching sessions, case reports, reviews, editorials, abstracts, and articles not in English were rejected. Three studies were identified following the exclusion criteria.
Results: All 3 studies received positive feedback from trainees regarding this technology in relation to enhanced surgical education. In addition, in all studies the trainees felt the technology had a place for educational training in the future. All studies described disadvantages to the technology as well including battery life, comfort, and cost.
Conclusions: Studies describe a big potential for Google Glass and similar head-mounted devices for the role of surgical training in urology, however, larger studies looking at more varied operations can help reinforce this viewpoint.
Keywords: Augmented reality; Education; Google glass; Head mounted display; Surgical training; Urology.
Thursday, 16 September 2021
WUTH publication: Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON
Author: Alexander J M Dingemans, Kim M G Truijen, Jung-Hyun Kim, Zahide Alaçam, Laurence Faivre, Kathleen M Collins, Erica H Gerkes, Mieke van Haelst, Ingrid M B H van de Laar, Kristin Lindstrom, Mathilde Nizon, James Pauling, Edyta Heropolitańska-Pliszka, Astrid S Plomp, Caroline Racine, Rani Sachdev, Margje Sinnema, Jon Skranes, Hermine E Veenstra-Knol, Eline A Verberne, Anneke T Vulto-van Silfhout, Marlon E F Wilsterman, Eun-Young Erin Ahn, Bert B A de Vries, Lisenka E L M Vissers
Abstract: Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Its encoded protein promotes pre-mRNA splicing of many genes essential for development. Whereas individual phenotypic traits have previously been linked to erroneous splicing of SON target genes, the phenotypic spectrum and the pathogenicity of missense variants have not been further evaluated. We present the phenotypic abnormalities in 52 individuals, including 17 individuals who have not been reported before. In total, loss-of-function variants were detected in 49 individuals (de novo in 47, inheritance unknown in 2), and in 3, a missense variant was observed (2 de novo, 1 inheritance unknown). Phenotypic abnormalities, systematically collected and analyzed in Human Phenotype Ontology, were found in all organ systems. Significant inter-individual phenotypic variability was observed, even in individuals with the same recurrent variant (n = 13). SON haploinsufficiency was previously shown to lead to downregulation of downstream genes, contributing to specific phenotypic features. Similar functional analysis for one missense variant, however, suggests a different mechanism than for heterozygous loss-of-function. Although small in numbers and while pathogenicity of these variants is not certain, these data allow for speculation whether de novo missense variants cause ZTTK syndrome via another mechanism, or a separate overlapping syndrome. In conclusion, heterozygous loss-of-function variants in SON define a recognizable syndrome, ZTTK, associated with a broad, severe phenotypic spectrum, characterized by a large inter-individual variability. These observations provide essential information for affected individuals, parents, and healthcare professionals to ensure appropriate clinical management.
Tuesday, 7 September 2021
WUTH publication: Never events in orthopaedics: A nationwide data analysis and guidance on preventative measures
Citation: The International Journal of Risk & Safety in Medicine. 2021 Aug 23. Online ahead of print.
Author: Ahmed T Hafez, Islam Omar, Balaji Purushothaman, Yusuf Michla, Kamal Mahawar
Abstract: Background: Never Events (NE) are serious clinical incidents that are wholly preventable if appropriate institutional safeguards are in place and followed. They are often used as a surrogate of the quality of healthcare delivered by an institution. Most NEs are surgical and orthopaedic surgery is one of the most involved specialties.
Objective: The aim of this study was to identify common NE themes associated with orthopaedics within the National Health Service (NHS) of England.
Method: We conducted an observational study analysing the annual NE data published by the NHS England from 2012 to 2020 to collate all orthopaedic surgery-related NE and construct relevant recurring themes.
Results: We identified 460 orthopaedic NE out of a total of 3247 (14.16%) reported NE to NHS England. There were 206 Wrong implants/prostheses under 8 different themes. Wrong hip and knee prosthesis were the commonest "wrong implants" (n = 94; 45.63% and n = 91; 44.17% respectively). There were 197 "Wrong-site surgery" incidents in 22 different themes. The commonest of these was the laterality problems accounting for 64 (32.48%) incidents followed by 63 (31.97%) incidents of wrong spinal level interventions. There were 18 (9.13%) incidents of intervention on the wrong patients and 17 (8.62%) wrong incisions. Retained pieces of instruments were the commonest retained foreign body with 15 (26.13%) incidents. The next categories were retained drill parts and retained instruments with 13 (22.80%) incidents each.
Conclusion: We identified 47 different themes of NE specific to orthopaedic surgery. Awareness of these themes would help in their prevention. Site marking can be challenging in the presence of cast and on operating on the digits and spine. Addition of a Real-time intra-operative implant scan to the National Joint Registry can avoid wrong implant selection while Fiducial markers, intraoperative imaging, O-arm navigation, and second time-out could help prevent wrong level spinal surgery.
Keywords: Orthopaedic surgery; medical claims; medical errors; never events; patient safety.
Thursday, 2 September 2021
WUTH publication: Prevalence of Falls in Patients Presenting to an Ophthalmic Outpatients Department- A Surveillance Study
Citation: The Biritsh and Irish Orthoptic Journal. 2021, 17(1), 134-41
Author: Jignasa Mehta, Karen Knowles, Erin Wilson
Abstract: Introduction: Approximately 1 in 3 adults aged 65 and over experience a fall each year. Poor vision is an identified risk factor. The aim of this cross-sectional public health surveillance audit was to determine the prevalence of falls experienced in the previous 12 months by adult patients presenting to an ophthalmology department.
Methods: A short questionnaire was given to consecutive patients attending an ophthalmology department at two trusts in the North West to determine whether they had experienced a fall in the previous 12 months, whether they had suffered a fracture, their eye condition and the type of glasses worn.
Results: Data was collected for 585 patients (mean age: 69 years, SD: 13.8). Falls in the previous 12 months were reported by 96 (16.4%) patients, and a significant proportion of these were aged 60 years and over (82%, p < 0.0001, one-sample binomial test). Half of the respondents were unaware of their eye health condition for which they were attending the department. Glaucoma was the most prevalent condition in those who had experienced a fall (43%). A significant proportion of the individuals who reported a fall wore single-vision glasses (43%, p < 0.0001, one-sample chi-square test).
Conclusion: In an ophthalmology outpatient department, the proportion of older adults who experienced a fall in the previous 12 months was lower than the reported prevalence in the general population. There is a need for health literacy to educate patients about their eye condition, the potential effects on their visual function and, consequently, managing falls risk.
Keywords: Falls; Ophthalmic conditions; Vision.
Tuesday, 31 August 2021
WUTH publication: Targeted atrial fibrillation (AF) detection in COVID-19 vaccination clinics
Author: Gary A Ford, David Hargroves, Deb Lowe, Nicholas Hicks, Gregory Y H Lip, Guy Rooney, Hannah Oatley
Thursday, 19 August 2021
WUTH publication: The prevalence of oropharyngeal squamous cell carcinoma in patients admitted with symptoms of peritonsillar abscess or cellulitis: a retrospective multicentre study
Author: Andrew S Lau, Kristijonas Milinis, Mila Roode, Stephen P Williams, Colette Cook, Hussein Walijee, Matthew Zammit, Richard Siau, Hannah Emerson, Rosanna Wright, Thomas Hampton
Abstract: Objectives: Anecdotal evidence suggests that oropharyngeal squamous cell carcinoma (OPSCC) should be suspected in patients presenting with symptoms of peritonsillar abscess (PTA) or cellulitis (PTC). The aim of this study was to estimate the prevalence of OPSCC in patients presenting with symptoms of PTA/PTC.
Monday, 9 August 2021
WUTH publication: Surgical and radiological predictive factors for ureteric stricture formation in patients treated with ureteroscopy for ureteric stones
Author: Zuhdi Al-Nabulsi, Yih Chyn Phan, Omer Abdalla, Tomas Austin, George Tanasescu, Peter Osborn, Andreas Auer, Carl Rowbotham, Mohamed Ismail
Thursday, 5 August 2021
WUTH publication: Localised Darier's disease: 3 cases of type 1 segmental mosaicism
Citation: Clinical and experimental dermatology. 2021 Aug 4. Online ahead of print.
Author: D Phillips, K Gumparthy, W C W Farrar, R Karumanchery, B B Tan
Abstract: Darier's Disease (DD) is an autosomal dominant acantholytic dermatosis with an estimated prevalence of 1:30000-1000001 . Onset is during childhood or adolescence2 and is characterised keratotic, crusted red-brown papules in a seborrhoeic distribution, nail changes (longitudinal erythronychia, longitudinal ridges and distal breakage with V-shaped notches) and palmar/plantar pits1 .
CCC publication: Characterization of liver function tests (LFTs) following tebentafusp (tebe) in previously treated (2L+) metastatic uveal melanoma (mUM) patients (pts)
CCC publication: Outcomes of immune checkpoint inhibitor-mediated colitis: Multicenter cohort study
Author: Abu-Sbeih H.; Tang T.; Faleck D.M.; Dougan M.L.; Olsson-Brown A.; Johnson D.B.; Owen D.H.; Warner D.E.; Philipp A.B.; Powell N.; Daniels E.; Philpott J.; Weppler A.M.; Pinato D.J.; Wang Y.
CCC publication: Co-primary endpoint of overall survival for tebentafusp (tebe)- induced rash in a phase 3 randomized trial comparing tebe versus investigator's choice (IC) in first-line metastatic uveal melanoma
Citation: Journal of Clinical Oncology. 2021, 39(15)
Author: Hassel J.C.; Rutkowski P.; Baurain J.-F.; Butler M.O.; Schlaak M.; Sullivan R.; Ochsenreither S.; Dummer R.; Kirkwood J.M.; Joshua A.M.; Sacco J.J.; Shoushtari A.N.; Orloff M.; Carvajal R.D.; Hamid O.; Abdullah S.E.; Holland C.; Goodall H.; Nathan P.; Piperno-Neumann S.
CCC publication: Overall survival in patients who received checkpoint inhibitors after completing tebentafusp in a phase 3 randomized trial of firstline metastatic uveal melanoma
Author: Orloff M.; Carvajal R.D.; Shoushtari A.N.; Sacco J.J.; Schlaak M.; Watkins C.; Abdullah S.E.; Goodall H.; Butler M.O.
CCC publication: Characterization of cytokine release syndrome (CRS) following treatment with tebentafusp in patients (pts) with previously treated (2L+) metastatic uveal melanoma (mUM)
Citation: Journal of Clinical Oncology. 2021, 39(15)
Author: Carvajal R.D.; Sato T.; Butler M.O.; Sacco J.J.; Shoushtari A.N.; Hassel J.C.; Ikeguchi A.; Hernandez-Aya L.F.; Rioth M.; Hamid O.; Piulats J.M.; Luke J.J.; Johnson D.B.; Leyvraz S.; Espinosa E.; Collins L.; McCully M.L.; Lockwood S.; Abdullah S.E.; Nathan P.
CCC publication: Real-world outcomes in older adults treated with immunotherapy: A United Kingdom multicenter series of 2,049 patients
Citation: Journal of Clinical Oncology. 2021, 39(15)
Author: Olsson-Brown A.C.; Baxter M.; Dobeson C.; Feeney L.; Lee R.; Maynard A.; Mirza S.; Parikh S.; Rodgers L.J.; Salawu A.; Shotton R.; Tinsley N.; Heseltine J.; Cotton J.; Hughes D.; Zhao S.; Parry J.; Jones C.; Rowe M.; Tivey A.
CCC publication: CORONET; COVID-19 in Oncology evaluatiON Tool: Use of machine learning to inform management of COVID-19 in patients with cancer
CCC publication: CAcTUS: A parallel arm, biomarker driven, phase II feasibility trial to determine the role of circulating tumor DNA in guiding a switch between targeted therapy and immune therapy in patients with advanced cutaneous melanoma
Citation: Journal of Clinical Oncology. 2021, 39(15)
Author: Lee R.; Rothwell D.G.; Chow S.; May Shaw H.; Turajlic S.; Smith N.; Clipson A.; Clarke H.; Kelso N.; Mitchell J.; Sutton C.; Sylvestre G.; Nathan P.D.; Larkin J.; Corrie P.G.; Plummer E.R.; Marais R.; Dive C.; Lorigan P.
CCC publication: Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study
CCC publication: Less chemotherapy for equal survival: Enhanced supportive care in hepatobiliary cancer
CCC publication: P-123 The impact of external carotid artery ligation on oropharyngeal bleeding following transoral laser surgery for oropharyngeal squamous cell cancer
Author: Dalton; Milinisa, Kristijonas; Houghton, David; Ridley, Paul; Davies, Katharine; Haridass, Anoop; Brammer, Caroline; Husband, David; Shenoy, Aditya; Loh, Christopher; Roland, Nicholas J.; Bekiroglu, Fazilet; Tandon, Sankalap; Lancaster, Jeffrey; Jones, Terence M.
CCC publication: P-109 CYTOFLOC: Evaluation of a non-endoscopic immunocytological device (Cytosponge™) for post-chemo-radiotherapy surveillance in patients with oesophageal cancer – a feasibility study,
Author: S. Mukherjee, H. O'Connor, R. Harman, M. O'Donovan, I. Debiram-Beecham, B. Alias, A. Bailey, A. Bateman, J. de Caestecker, T. Crosby, S. Falk, S. Gollins, M. Hawkins, S. Levy, G. Radhakrishna, R. Roy, R. Sripadam, R. Fitzgerald
CCC publication: Beyond the lessons learned from the Covid19 pandemic: Opportunities to optimize clinical trial implementation in oncology
Author: Luis Castelo-Branco, Ahmad Awada, George Pentheroudakis, Jose Luis Perez-Garcia, Joaquin Mateo, Giuseppe Curigliano, Susana Banerjee, Rosa Giuliani, Florian Lordick, Andres Cervantes, Josep Tabernero, Solange Peters
Abstract: The COVID-19 pandemic affected millions of people globally with lasting effects on society, patients, investigators and health institutions. Clinical trials, our best tool to improve cancer treatment for patients through testing the clinical value of a new treatment, have been affected by the pandemic. The pandemic footprint represents both a risk of compromising development of new therapies and an opportunity to elicit discussion over a portfolio of broader reforms, applicable irrespective of pandemics, in order to improve the design and implementation of clinical trials in oncology. The administrative load should be reduced, without affecting the quality of research and principles of good clinical practice. Cancer centres are encouraged to adapt their research/operational structures to the requirements of molecular oncology and embrace novel trial designs. Technological and methodological leaps in telemedicine can convert physical to virtual visits while routine examinations may be performed in local institutions (co-research centres), maintaining adherence to good clinical and research practices. The adoption of broader inclusion criteria and clinically significant endpoints (survival, quality of life) should be promoted, co-existing with pathways for fast-track “conditional†drug approvals in areas of unmet need, based on surrogate endpoints that are linked to strict post-approval validation requirements. The utility of Real World Data as part of these validation requirements should be actively investigated. Lessons learnt from the SARS Cov2 pandemic can be developed in order to expand equitable access to clinical trials of a real world population, in a simplified and methodologically robust modus operandi, for the benefit of all our patients.
CCC publication: USP9X Is Required to Maintain Cell Survival in Response to High-LET Radiation
Author: Catherine M Nickson, Maria Rita Fabbrizi, Rachel J Carter, Jonathan R Hughes, Andrzej Kacperek, Mark A Hill, Jason L Parsons
Abstract: Ionizing radiation (IR) principally acts through induction of DNA damage that promotes cell death, although the biological effects of IR are more broad ranging. In fact, the impact of IR of higher-linear energy transfer (LET) on cell biology is generally not well understood. Critically, therefore, the cellular enzymes and mechanisms responsible for enhancing cell survival following high-LET IR are unclear. To this effect, we have recently performed siRNA screening to identify deubiquitylating enzymes that control cell survival specifically in response to high-LET α-particles and protons, in comparison to low-LET X-rays and protons. From this screening, we have now thoroughly validated that depletion of the ubiquitin-specific protease 9X (USP9X) in HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells using small interfering RNA (siRNA), leads to significantly decreased survival of cells after high-LET radiation. We consequently investigated the mechanism through which this occurs, and demonstrate that an absence of USP9X has no impact on DNA damage repair post-irradiation nor on apoptosis, autophagy, or senescence. We discovered that USP9X is required to stabilize key proteins (CEP55 and CEP131) involved in centrosome and cilia formation and plays an important role in controlling pericentrin-rich foci, particularly in response to high-LET protons. This was also confirmed directly by demonstrating that depletion of CEP55/CEP131 led to both enhanced radiosensitivity of cells to high-LET protons and amplification of pericentrin-rich foci. Our evidence supports the importance of USP9X in maintaining centrosome function and biogenesis and which is crucial particularly in the cellular response to high-LET radiation.
CCC publication: A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic
Author: Ifigenia Vasiliadou, David Noble, Andrew Hartley, Rafael Moleron, Paul Sanghera, Teresa Guerrero Urbano, Stefano Schipani, Dorothy Gujral, Bernie Foran, Shree Bhide, Anoop Haridass, Kannon Nathan, Andriana Michaelidou, Mehmet Sen, Konstantinos Geropantas, Mano Joseph, Lorcan O'Toole, Matthew Griffin, Laura Pettit, Jonathan Chambers, Petra Jankowska, Emma De Winton, Rebecca Goranova, Niveditha Singh, Ketan Shah, Anthony Kong Conceptualisation
Abstract: Background: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK.
CCC publication: Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphom
Citation: Haematologica. 2021 Jul 1. Online ahead of print.
Author: Johannes Duell, Kami J Maddocks, Eva González-Barca, Wojciech Jurczak, Anna Marina Liberati, Sven De Vos, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Pau Abrisqueta, Nagesh Kalakonda, Marc André, Martin Dreyling, Tobias Menne, Olivier Tournilhac, Marinela Augustin, Andreas Rosenwald, Maren Dirnberger-Hertweck, Johannes Weirather, Sumeet Ambarkhane, Gilles Salles
Abstract: Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study (NCT02399085) of autologous stem-cell transplant (ASCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had 1-3 prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression (PD). The primary endpoint was best objective response rate (ORR). After ≥35 months' follow-up (data cut-off: October 30, 2020), ORR was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). Median duration of response (DoR) was 43.9 months (95% CI: 26.1-not reached [NR]); median overall survival (OS) was 33.5 months (18.3-NR); and median progression-free survival was 11.6 months (6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most patient subgroups. This extended L-MIND follow-up confirms the long DoR, meaningful OS, and welldefined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in ASCT-ineligible patients with R/R DLBCL.
CCC publication: Second-line FOLFOX chemotherapy for advanced biliary tract cancer - Authors' reply
Author: Angela Lamarca, Daniel H Palmer, Harpreet Singh Wasan, Paul J Ross, Yuk Ting Ma, Arvind Arora, Stephen Falk, Roopinder Gillmore, Jonathan Wadsley, Kinnari Patel, Alan Anthoney, Anthony Maraveyas, Tim Iveson, Justin S Waters, Claire Hobbs, Safia Barber, W David Ryder, John Ramage, Linda M Davies, John A Bridgewater, Juan W Valle, Advanced Biliary Cancer Working Group
CCC publication: Clinically Applicable Segmentation of Head and Neck Anatomy for Radiotherapy: Deep Learning Algorithm Development and Validation Study
Author: Stanislav Nikolov, Sam Blackwell, Alexei Zverovitch, Ruheena Mendes, Michelle Livne, Jeffrey De Fauw, Yojan Patel, Clemens Meyer, Harry Askham, Bernadino Romera-Paredes, Christopher Kelly, Alan Karthikesalingam, Carlton Chu, Dawn Carnell, Cheng Boon, Derek D'Souza, Syed Ali Moinuddin, Bethany Garie, Yasmin McQuinlan, Sarah Ireland, Kiarna Hampton, Krystle Fuller, Hugh Montgomery, Geraint Rees, Mustafa Suleyman, Trevor Back, Cían Owen Hughes, Joseph R Ledsam, Olaf Ronneberger
CCC publication: Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial
Author: R Charles Coombes, Holly Tovey, Lucy Kilburn, Janine Mansi, Carlo Palmieri, John Bartlett, Jonathan Hicks, Andreas Makris, Abigail Evans, Sibylle Loibl, Carsten Denkert, Elisabeth Murray, Robert Grieve, Robert Coleman, Annabel Borley, Marcus Schmidt, Beate Rautenberg, Catarina Alisa Kunze, Uwe Rhein, Keyur Mehta, Kelly Mousa, Tessa Dibble, Xiao Lou Lu, Gunter von Minckwitz, Judith M Bliss, Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators
Abstract: Importance: Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking.
CCC publication: Genome-wide association studies of toxicity to oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab in 1800 patients with advanced colorectal cancer
Citation: International Journal of Cancer. 2021 Jul 16. Online ahead of print.
Author: Katie Watts, Christopher Wills, Ayman Madi, Claire Palles, Timothy S Maughan, Richard Kaplan, Nada A Al-Tassan, Rachel Kerr, David Kerr, Victoria Gray, Hannah West, Richard S Houlston, Valentina Escott-Price, Jeremy P Cheadle
Abstract: Chemotherapies administered at normal therapeutic dosages can cause significant side-effects and may result in early treatment discontinuation. Inter-individual variation in toxicity highlights the need for biomarkers to personalise treatment. We sought to identify such biomarkers by conducting 40 genome-wide association studies, together with gene and gene set analyses, for any toxicity and 10 individual toxicities in 1800 patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab from the MRC COIN and COIN-B trials (385 patients received FOLFOX, 360 FOLFOX + cetuximab, 707 XELOX and 348 XELOX + cetuximab). Single nucleotide polymorphisms (SNPs), genes and gene sets that reached genome-wide or suggestive significance were validated in independent patient groups. We found that MROH5 was significantly associated with neutropenia in MAGMA gene analyses in patients treated with XELOX (P = 6.6 × 10-7 ) and was independently validated in those receiving XELOX + cetuximab; pooled P = 3.7 × 10-7 . rs13260246 at 8q21.13 was significantly associated with vomiting in patients treated with XELOX (odds ratio = 5.0, 95% confidence interval = 3.0-8.3, P = 9.8 × 10-10 ) but was not independently replicated. SNPs at 139 loci had suggestive associations for toxicities and lead SNPs at five of these were independently validated (rs6030266 with diarrhoea, rs1546161 with hand-foot syndrome, rs9601722 with neutropenia, rs13413764 with lethargy and rs4600090 with nausea; all with pooled P's < 5.0 × 10-6 ). In conclusion, the association of MROH5 with neutropenia and five other putative biomarkers warrant further investigation for their potential clinical utility. Despite our comprehensive genome-wide analyses of large, well-characterised, clinical trials, we found a lack of common variants with modest effect sizes associated with toxicities.
Keywords: GWAS; chemotherapy; colorectal cancer; toxicity.
CCC publication: A multi-centre analysis of adjuvant contact x-ray brachytherapy (CXB) in rectal cancer patients treated with local excision - preliminary results of the CONTEM1 study
Author: A Dhadda, A Sun Myint, B Thamphya, I Hunter, M Hershman, J Gerard
Abstract: Introduction: Early rectal cancers are increasingly diagnosed through screening programmes and are often treated using local excision (LE). In the case of adverse pathological features completion total mesorectal excision surgery (TME) is the standard recommendation. The morbidity and mortality risks of TME have stimulated the use of adjunctive treatments following LE to achieve organ preservation.
CCC publication: Proton beam therapy in rectal cancer: A systematic review and meta-analysis
Author: Matthew Fok, Steven Toh, Jeremy Easow, Hayley Fowler, Rachael Clifford, Jason Parsons, Dale Vimalachandran
Abstract: Introduction: Locally advanced rectal cancer is often treated with neoadjuvant chemoradiotherapy and surgery. Radiotherapy carries significant risk of toxicity to organs at risk (OAR). Proton beam therapy (PBT) has demonstrated to be effective in other cancers, delivering equivalent dosimetric radiation but with the benefit of improved sparing of OAR. This review compares dosimetric irradiation of OAR and oncological outcomes for PBT versus conventional photon-based radiotherapy in locally advanced rectal cancer.
Monday, 2 August 2021
WUTH publication: Hematopoietic stem and progenitor cells directly participate in host immune response
Author: Olusola Jumoke Daramola, Stephen Osasan, Hebah Ali, Perpetua Emeagi
Abstract: The properties of hematopoietic stem and progenitor cells (HSPCs), including self-renewal and pluripotency, have been extensively studied. These features have been explored in the management of several haematological disorders and malignancies. Although their role as precursors of innate immune cells is well understood, little is known about their direct participation in host immune response. In this review, we explicate the direct role of HSPCs in the host immune response and highlight therapeutic options for the infectious disease burden that is currently ravaging the world, including COVID-19.
Tuesday, 27 July 2021
WUTH publication: An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs
Author: Heather J Cordell, James J Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D Juran, Elizabeth J Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A R Ferreira, Dylan Sun, David E Jones, Steven Flack, Ann Spicer, Victoria L Mulcahy, Jinyoung Byan, Younghun Han, Richard N Sandford, Konstantinos N Lazaridis, Christopher I Amos, Gideon M Hirschfield, Michael F Seldin, Pietro Invernizzi, Katherine A Siminovitch, Xiong Ma, Minoru Nakamura, George F Mells, PBC Consortia; Canadian PBC Consortium; Chinese PBC Consortium; Italian PBC Study Group; Japan-PBC-GWAS Consortium; US PBC Consortium; UK-PBC Consortium
Abstract: Backgrounds & aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
Thursday, 22 July 2021
WUTH publication: A study of the role and educational needs of ophthalmic specialist nurses
Author: Pornjittra Rattanasirivilai, Amy-Lee Shirodkar
Abstract: Aims: To explore the current roles, responsibilities and educational needs of ophthalmic specialist nurses (OSNs) in the UK.
Tuesday, 6 July 2021
WUTH publication: Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital
Citation: Therapeutic advances in psychopharmacology. 2021 Jun 21. eCollection 2021
Author: Edward Silva, Melanie Higgins, Barbara Hammer, Paul Stephenson
Abstract: Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia; however, its use is prohibited following neutropenias. We review neutrophil biology as applied to clozapine and describe the strategies to initiate clozapine following neutropenia used in a case series of 14 consecutive patients rechallenged in a United Kingdom (UK) high-secure psychiatric hospital. We examine outcomes including the use of seclusion and transfer.
Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using this routinely collected clinical data, we describe the patient characteristics, causes of neutropenia, the strategies used for rechallenging with clozapine and clinical outcomes.
Results: Previous neutropenias were the result of benign ethnic neutropenia, clozapine, other medications and autoimmune-related. Our risk mitigation strategies included: granulocyte-colony stimulating factor (G-CSF), lithium and watch-and-wait. There were no serious adverse events; at follow up half of the patient's had improved sufficiently to transfer them to conditions of lesser security. There were dramatic reductions in the use of seclusion.
Conclusion: Even in this extreme group, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients. This requires careful planning based on an understanding of neutrophil biology and the aetiology of the specific episode of neutropenia.
Keywords: agranulocytosis; antipsychotic agents; clozapine; forensic; granulocyte-colony-stimulating factor; lithium; neutrophils; schizophrenia; seclusion.
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Thursday, 1 July 2021
Health Information Week 5th-11th July #HIW2021
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Monday, 28 June 2021
WUTH publication: Psychological distress and trauma during the COVID-19 pandemic: survey of doctors practising anaesthesia, intensive care medicine, and emergency medicine in the United Kingdom and Republic of Ireland
Author: Tom Roberts, Robert Hirst, Camilla Sammut-Powell, Charles Reynard, Jo Daniels, Daniel Horner, Mark D Lyttle, Katie Samuel, Blair Graham, Michael J Barrett, James Foley, John Cronin, Etimbuk Umana, Joao Vinagre, Edward Carlton, TERN; PERUKI; I-TERN; RAFT, TRIC and SATURN Collaborators
Abstract: Keywords: COVID-19; anaesthesia; emergency medicine; intensive care; mental health; psychological trauma.
Thursday, 24 June 2021
CCC publication: Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases
Author: Richard S P Huang, James Haberberger, Kimberly McGregor, Douglas A Mata, Brennan Decker, Matthew C Hiemenz, Mirna Lechpammer, Natalie Danziger, Kelsie Schiavone, James Creeden, Ryon P Graf, Roy Strowd, Glenn J Lesser, Evangelia D Razis, Rupert Bartsch, Athina Giannoudis, Talvinder Bhogal, Nancy U Lin, Lajos Pusztai, Jeffrey S Ross, Carlo Palmieri, Shakti H Ramkissoon
Abstract: Background: Among patients with breast carcinoma who have metastatic disease, 15%-30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of patients with breast carcinoma brain metastases (BCBMs) and compared it with a cohort of patients with primary breast carcinomas (BCs).
CCC publication: A review of the evidence base for utilizing Child-Pugh criteria for guiding dosing of anticancer drugs in patients with cancer and liver impairment
Citation: ESMO Open. 2021, 6(3), 100162. Epub 2021 Jun 5
Author: C Palmieri, I R Macpherson
Abstract: As the liver is vital for the metabolism of many anticancer drugs, determining the correct starting doses in cancer patients with liver impairment is key to safe prescription and prevention of unnecessary adverse effects. Clinicians typically use liver function tests when evaluating patients; however, prescribing information and summaries of product characteristics often suggest dosing of anticancer drugs in patients with liver impairment based on the Child-Pugh criteria, even though the criteria were not developed for this purpose. In this review, we assessed all the oncological small molecule and cytotoxic drugs approved by the United States Food and Drug Administration (FDA) over a 5-year period from 2014 to 2018. The various entry criteria related to these drugs-with respect to hepatic function-in key pivotal studies were compared with their approved dosing recommendations found in prescribing information and summaries of product characteristics. We found that 46% of drugs have dosing recommendations based on Child-Pugh criteria alone, despite the fact that only 8% of these drugs were tested within studies that used the Child-Pugh criteria as entry criteria. Moreover, we note that the data used to make recommendations based on Child-Pugh criteria are typically from small studies that may lack an appropriate patient population. We propose that these findings, along with details surrounding the development of the Child-Pugh criteria, call into question the validity and appropriateness of using Child-Pugh criteria for dosing recommendations of anticancer drugs.
Keywords: Child-Pugh criteria; anticancer drugs; dosing; liver impairment.
CCC publication: Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
Citation: Radiation Oncology. 2021, 16(1), 95
Author: Louise Turtle, Neeraj Bhalla, Andrew Willett, Robert Biggar, Jonathan Leadbetter, Georgios Georgiou, James M Wilson, Sindu Vivekanandan, Maria A Hawkins, Michael Brada, John D Fenwick
Abstract: Background: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC).
Materials and methods: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy).
Results: Following re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values.
Conclusions: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.
Keywords: Cardiac-sparing; Heart; NSCLC; Radiotherapy; Survival.
CCC publication: Long-term outcomes of patients with poor prognostic factors following transanal endoscopic microsurgery for early rectal cancer
Author: Muhammad A Javed, Sarah Shamim, Simone Slawik, Timothy Andrews, Amir Montazeri, Shakil Ahmed
Abstract: Aim: Management of early rectal cancer following transanal microscopic anal surgery poses a management dilemma when the histopathology reveals poor prognostic features, due to high risk of local recurrence. The aim of this study is to evaluate the oncological outcomes of such patients who undergo surgery with total mesorectal excision (TME), receive adjuvant chemo/radiotherapy (CRDT/RT) or receive close surveillance only (no further treatment).