Author: Jason Curtis

Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial (2023)

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Type of publication:
Journal article

Author(s):
Nutting C.; Finneran L.; Roe J.; Sydenham M.A.; Beasley M.; Bhide S.; Boon C.; Cook A.; De Winton E.; Emson M.; Foran B.; Frogley R.; Petkar I.; *Pettit L.; Rooney K.; Roques T.; Srinivasan D.; Tyler J.; Hall E.

Citation:
Lancet Oncology. 24(8):868-880, August 2023

Abstract:
BACKGROUND: Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT. METHOD(S): DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete. FINDINGS: From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39.5 months (IQR 37.8-50.0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77.7 [SD 16.1] vs 70.6 [17.3]; mean difference 7.2 [95% CI 0.4-13.9]; p=0.037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths. INTERPRETATION: Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers. FUNDING: Cancer Research UK.

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Management And Assessment Of Indeterminate (U3) Thyroid Nodules: A 5-Year Multisite Retrospective Study (2023)

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Type of publication:
Journal article

Author(s):
*Patel R.; *Conybeare A.; *Panesar H.; *Badrol S.; *Sood S.

Citation:
Journal of Ayub Medical College, Abbottabad : JAMC. 35(2) (pp 216-219), April 2023.

Abstract:
BACKGROUND: The U grading of Ultrasound scan (USS) is used to assess the likelihood of malignancy in a thyroid nodule and help determine those that warrant an FNAC confirmation. All those of a U3-5 warrant an FNAC for confirmation and typing. This study aims to review the follow-up practice and the likelihood of picking up a malignancy on subsequent USS and FNAC, for those determined as an indeterminate U3 nodule. METHOD(S): We retrospective reviewed the trust database (Portal) for patients who had a U3 nodule reported on USS identified, and clinical, operative and outcomes data were analysed. RESULT(S): 258 scans were identified over a 5-year period. The average age was 59 (range 15- 95) years old at first USS with a female to the male sex ratio of 4:1. The average number of USS that each patient prior to final diagnosis had averaged at 2.8 (range 1-12). Of those with an initial Thy status, 64 (33%) were benign (Thy2) and a further 49 (25%) were non diagnostics (Thy1). Over time, only 7 nodules were upgraded to a potential malignancy. Of those who underwent surgery, a final histological diagnosis was obtained in 41 cases. Only Thy1, 2 and 3f produced benign final histology results. CONCLUSION(S): For those indeterminate (U3) nodules of Th1-3f, electing for a watch and wait management strategy is reasonable for up to 2.5 years and 4 follow-up scans at an interval of 6-12 months should be implemented. A Thy2 result on a U3 nodule should not be taken as completely reassuring, a high index of suspicion of malignancy must be maintained.

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An overview of bone cement: Perioperative considerations, complications, outcomes and future implications. (2023)

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Type of publication:
Journal article

Author(s):
*Patel, Ravi; Mcconaghie, Greg; Webb, Jeremy; Laing, Georgina; *Roach, Richard; Banerjee, Robin.

Citation:
Journal of Perioperative Practice. 2023 May 26. [epub ahead of print]

Abstract:
Polymethyl methacrylate is commonly known as bone cement and is widely used for implant fixation in various orthopaedic arthroplasty and trauma surgery. The first bone cement use in orthopaedics is widely accredited to the famous English surgeon, John Charnley, who in 1958, used it for total hip arthroplasty. Since then, there have been many developments in cementing techniques in arthroplasty surgery. This overview aims to cover the perioperative considerations of bone cement, including cementing techniques, current outcomes and complications such as bone cement implantation syndrome. The overview will additionally consider future developments involving bone cement in orthopaedic arthroplasty.

Rheumatoid nodule presenting as an indeterminate soft tissue mass in the sole of the foot (2023)

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Type of publication:
Journal article

Author(s):
*Patel R.; Nand R.; Sunderamoorthy D.

Citation:
Journal of Surgical Case Reports. 2023(5) (no pagination), May 2023.

Abstract:
A 64-year-old lady with a background of rheumatoid arthritis presented to the foot and ankle clinic with lump underneath the sole of her foot causing significant discomfort. Examination revealed she had a swelling of the first and the second metatarsophalangeal joints. Magnetic resonance imaging revealed abnormal soft tissue thickening between the second and the third metatarsal and a single large encapsulating indeterminate soft tissue mass with a peripheral inflammatory rim. The appearance was suggestive of a malignant sarcoma rather than a rheumatoid nodule or rheumatoid tenosynovitis. The patient was referred to the regional sarcoma unit where the scans were reviewed, and a sarcoma was ruled out. The patient then underwent excision of the indeterminate soft tissue mass. Histology revealed granulomatous infiltration suggestive of a rheumatoid nodule. This has not been described previously in the literature.

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Focused transoesophageal TOE (fTOE): A new accreditation pathway (2023)

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Type of publication:
Journal article

Author(s):
Rubino A.; Peck M.; *Miller A.; Edmiston T.; Klein A.A.; Orme R.; Sankar V.; Fletcher N.; O'Keeffe N.; Skinner H.

Citation:
Journal of the Intensive Care Society. Date of Publication: 2023. [epub ahead of print]

Abstract:
The concept of a focused ultrasound study to identify sources of haemodynamic instability has revolutionized patient care. Point-of-care ultrasound (POCUS) using transthoracic scanning protocols, such as FUSIC Heart, has empowered non-cardiologists to rapidly identify and treat the major causes of haemodynamic instability. There are, however, circumstances when a transoesphageal, rather than transthoracic approach, may be preferrable. Due to the close anatomical proximity between the oesophagus, stomach and heart, a transoesphageal echocardiogram (TOE) can potentially overcome many of the limitations encountered in patients with poor transthoracic ultrasound windows. These are typically patients with severe obesity, chest wall injuries, inability to lie in the left lateral decubitus position and those receiving high levels of positive airway pressure. In 2022, to provide all acute care practitioners with the opportunity to acquire competency in focused TOE, the Intensive Care Society (ICS) and Association of Anaesthetists (AA) launched a new accreditation pathway, known as Focused Transoesophageal Echo (fTOE). The aim of fTOE is to provide the practitioner with the necessary information to identify the aetiology of haemodynamic instability. Focused TOE can be taught in a shorter period of time than comprehensive and teaching programmes are achievable with support from cardiothoracic anaesthetists, intensivists and cardiologists. Registration for fTOE accreditation requires registration via the ICS website. Learning material include theoretical modules, clinical cases and multiple-choice questions. Fifty fTOE examinations are required for the logbook, and these must cover a range of pathology, including ventricular dysfunction, pericardial effusion, tamponade, pleural effusion and low preload. The final practical assessment may be undertaken when the supervisors deem the candidate's knowledge and skills consistent with that required for independent practice. After the practitioner has been accredited in fTOE, they must maintain knowledge and competence through relevant continuing medical education. Accreditation in fTOE represents a joint venture between the ICS and AA and is endorsed by Association of Cardiothoracic Anaesthesia and Critical care (ACTACC). The process is led by TOE experts, and represents a valuable expansion in the armamentarium of acute care practitioners to assess haemodynamically unstable patients.

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Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol (2023)

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Type of publication:
Journal article

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Sachdeva, Ashwin; Jones, Craig; Hoyle, Alex; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Gilson, Clare; Rush, Hannah; Abdel-Aty, Hoda; Amos, Claire L; Murphy, Claire; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Parkar, Nazia; Pugh, Cheryl; Diaz-Montana, Carlos; Pezaro, Carmel; Grant, Warren; Saxby, Helen; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzouebi, Mymoona; Parikh, Omi; Robinson, Angus; Montazeri, Amir H; Wylie, James; Zarkar, Anjali; Cathomas, Richard; Brown, Michael D; Jain, Yatin; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D.

Citation:
Lancet Oncology. 24(5):443-456, 2023 May.

Abstract:
BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76.6 months (95% CI 67.8-86.9) in the abiraterone group versus 45.7 months (41.6-52.0) in the standard of care group (hazard ratio [HR] 0.62 [95% CI 0.53-0.73]; p<0.0001). In the abiraterone and enzalutamide trial, median overall survival was 73.1 months (61.9-81.3) in the abiraterone and enzalutamide group versus 51.8 months (45.3-59.0) in the standard of care group (HR 0.65 [0.55-0.77]; p<0.0001). We found no difference in the treatment effect between these two trials (interaction HR 1.05 [0.83-1.32]; pinteraction=0.71) or between-trial heterogeneity (I2 p=0.70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.

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MYC/BCL6 Double Hit Lymphoma Negative For (3;8) BCL6:MYC Fusion is Associated With Inferior Survival, in Contrast with T(3;8) Positive Pseudo-Double Hit Lymphoma (2023)

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Type of publication:
Conference abstract

Author(s):
Maybury, B. D.; James, L.; Chadderton, N.; Dowds, J.; Venkatadasari, I.; Riley, J.; Qureshi, I.; Talbot, G.; Giles, H. V.; Phillips, N. J.; Gonzalez, M. Vega; Rakesh, P.; Haslam, A.; Davies, D.; Moosai, S.; Lane, S. A.; *Shenouda, A.; Cherian, G. V.; Kaudlay, P. K.;Starczynski, J.; et al

Citation:
Hematological Oncology, June 2023 Supplement 1; 41: 205-207.

Abstract:

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The SSS revolution in fungal diagnostics: speed, simplicity and sensitivity (2023)

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Type of publication:
Journal article

Author(s):
*Baker, Jacob; Denning, David W.

Citation:
British Medical Bulletin. 147(1):62-78, 2023 Sep 12.

Abstract:
INTRODUCTION: Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive and time-intensive fungal culture. SOURCES OF DATA: We present the recent developments in fungal diagnostics in the fields of serological and molecular diagnosis for the most clinically relevant pathogens; developments that have the potential to revolutionize fungal diagnosis through improvements in speed, simplicity and sensitivity. We have drawn on a body of evidence including recent studies and reviews demonstrating the effectiveness of antigen and antibody detection and polymerase chain reaction (PCR) in patients with and without concurrent human immunodeficiency virus infection. AREAS OF AGREEMENT: This includes recently developed fungal lateral flow assays, which have a low cost and operator skill requirement that give them great applicability to low-resource settings. Antigen detection for Cryptococcus, Histoplasma and Aspergillus spp. are much more sensitive than culture. PCR for Candida spp., Aspergillus spp., Mucorales and Pneumocystis jirovecii is more sensitive than culture and usually faster. AREAS OF CONTROVERSY: Effort must be made to utilize recent developments in fungal diagnostics in clinical settings outside of specialist centres and integrate their use into standard medical practice. Given the clinical similarities of the conditions and frequent co-infection, further study is required into the use of serological and molecular fungal tests, particularly in patients being treated for tuberculosis. GROWING POINTS: Further study is needed to clarify the utility of these tests in low-resource settings confounded by a high prevalence of tuberculosis. AREAS TIMELY FOR DEVELOPING RESEARCH: The diagnostic utility of these tests may require revision of laboratory work flows, care pathways and clinical and lab coordination, especially for any facility caring for the immunosuppressed, critically ill or those with chronic chest conditions, in whom fungal disease is common and underappreciated.

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Correlative effect between sac regression and clinical outcomes following endovascular repair in abdominal aortic aneurysm: fact or myth? (2023)

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Type of publication:
Journal article

Author(s):
Al-Tawil, Mohammed; Muscogliati, Eduardo; Jubouri, Matti; Saha, Priyanshu; *Patel, Ravi; Mohammed, Idhrees; Bailey, Damian M; Williams, Ian M; Bashir, Mohamad

Citation:
Expert Review of Medical Devices. 1-8, 2023 Jun 16

Abstract:
INTRODUCTION: Endovascular aneurysm repair (EVAR) has rapidly become the preferred management of abdominal aortic aneurysm (AAA). Sac regression status post-EVAR has been linked to clinical outcomes as well as the choice of EVAR device. The aim of this narrative review is to investigate the relationship between sac regression and clinical outcomes post-EVAR in AAA. Another aim is to compare sac regression achieved with the main EVAR devices. AREAS COVERED: We carried out a comprehensive literature search on multiple electronic databases. Sac regression was usually defined as a decrease in the sac diameter (>10 mm) over follow-up. This revealed that individuals who had sac regression post-EVAR had significantly lower mortality, and higher event-free survival rates. Further, lower rates of endoleak and reintervention were observed in patients with regressing aneurysm sacs. Sac regression patients also had significantly lower odds of rupture compared to counterparts with stable or expanded sacs. The choice of EVAR device was also shown to impact regression, with the Fenestrated Anaconda showing favorable results. EXPERT OPINION: Sac regression post-EVAR in AAA is an important prognostic factor as it translates to improved mortality and morbidity. Therefore, this relationship must be seriously taken into consideration during follow-up.

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Cardiovascular disease morbidity is associated with social deprivation in subjects with familial hypercholesterolaemia (FH): a study comparing FH individuals in UK primary care and the UK Simon Broome register linked with secondary care records (2022)

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Type of publication:
Conference abstract

Author(s):
Iyen B.; Qureshi N.; Roderick P.; *Capps N.; Durrington P.N.; McDowell I.F.W.; Cegla J.; Soran H.; Schofield J.; Neil H.A.W.; Kai J.; Weng S.; Humphries S.E.

Citation:
Atherosclerosis Plus. Conference: HEART UK 35th Annual Medical & Scientific Conference. Virtual. 49(Supplement 1) (pp S4-S5), 2022. Date of Publication: October 2022

Abstract:
Background: Measures of social deprivation are associated with higher cardiovascular diseases (CVD) morbidity and mortality. To determine if this is also seen in subjects with Familial Hypercholesterolaemia (FH), CVD morbidity has been examined in participants in the UK primary care database (CPRD) and in the UK Simon Broome (SB) register using linkage to the UK secondary care Hospital Episodes Statistics (HES). Method(s): A composite CVD outcome was analysed (first HES outcome of coronary heart disease, myocardial infarction, stable or unstable angina, stroke, TIA, PVD, heart failure, PCI and CABG). The measure of socio-economic status/deprivation used was the English index of multiple deprivation (IMD). Cox proportional hazards regression estimated hazards ratios (HR) for incident CVD and mortality [95% CI] in each IMD quintile. <br/>Result(s): We identified 4,309 patients with FH in UK CPRD primary care database (followed from 1988 to 2020), free from CVD, and 2988 SB register participants, with linked secondary care HES records. In both groups, the prevalence of FH was considerably lower in the most deprived quintile (60% in CPRD and 52% in SB). CPRD patients in the most deprived quintile (IMD-5) had the highest prevalence of obesity and of smoking compared to those from IMD quintiles 1,2,3 and 4 (p-value for trend, all <0.001). Compared to least deprived, the most deprived individuals had the highest risk of composite CVD (unadjusted HR 1.71 [CI 1.22-2.40]), however, on adjustment for smoking and alcohol consumption, there were no statistical differences in CVD risk between socio-economic groups. In the FH Register patients there was an increase in the incidence rates and hazards ratios for composite CVD with increasing quintiles of deprivation. After adjustment for age, sex, smoking and alcohol consumption, this effect remained statistically significant (quintile 5 vs 1, HR = 1.83 [1.54-2.17]. Conclusion(s): Patients with FH are underdiagnosed in lower socio-economic groups. In both CPRD and the SB Register the most deprived FH patients had the highest risk of CVD and mortality, but in CPRD but not in the SB register this was largely explained by smoking and alcohol consumption. Clinicians should adopt more effective strategies to detect FH in lower socio-economic groups, and to optimise risk factor management and to support lifestyle changes and medication adherence for this group.

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