2020

Global longitudinal strain detects trastuzumab induced cardiotoxicity early in a clinical population (2020)

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Type of publication:
Conference abstract

Author(s):
*Grylls, J., *Ellis, C., *Ingram, T., *Lee, E.

Citation:
European Heart Journal – Cardiovascular Imaging 2020; Volume 21, Issue Supplement 1

Abstract:
Background: Trastuzumab is highly effective in the treatment of breast cancer, and is often used as an adjuvant therapy. Due to its potential cardiotoxicity, serial monitoring of cardiac function is vital. Ejection fraction (EF) by two-dimensional echocardiography is routinely used but has limitations in measurement variability. Myocardial deformation imaging, in particular Global Longitudinal Strain (GLS), can detect pre-clinical myocardial dysfunction. However, its use is not yet adopted into routine clinical practice.
Aims: Our aim was to ascertain if a clinically significant reduction in GLS (≥11% from baseline) occurred before the onset of EF reduction, in patients who developed cardiotoxicity whilst receiving trastuzumab.
Methods: Between January 2014 and January 2019, 235 consecutive patients received trastuzumab and underwent serial echocardiography at 3 monthly intervals at our institute. Cardiotoxicity is defined as a ≥10% EF reduction from baseline or an EF <50%. Women who developed cardiotoxicity as defined by this change in EF were retrospectively studied.Two-dimensional speckle tracking was used to derive peak longitudinal strain in each myocardial segment from the apical four-, three- and two-chamber view images. GLS was taken as the average value of all these segments. The median time to ≥11% GLS reduction and ≥10% EF reduction or EF <50% was compared.
Results: Thirteen women (mean age 53 ± 9.5 years) developed cardiotoxicity. EF was 61.8 ± 4.4% at baseline and 45.7 ± 7.5% following therapy (p = 0.00). A ≥11% reduction in GLS from baseline was observed in all patients: GLS -20.2 ± 1.5% and -15.6 ± 2.1%, p = 0.00. The median time to cardiotoxicity as defined by EF and GLS was 6 months and 3 months, respectively (p = 0.031), as shown in Table 1. Repeatability analysis showed both EF and GLS measurements in our cohort have good measurement reproducibility. Inter-observer intraclass correlation (ICC) for EF and GLS were 0.912 and 0.913, respectively. Intra-observer ICC for EF and GLS were 0.925 and 0.900, respectively.
Conclusion: Cardiotoxicity developed in a significant portion (6%) of our patients receiving trastuzumab. As a reduction in GLS was detectable early and preceded that of EF by 3 months, this may represent a therapeutic window for initiation of cardio-protective medication, if and when the use of GLS is incorporated into routine practice for cardiotoxicity surveillance.

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Evaluating the Trade-offs Men with Localised Prostate Cancer Make Between the Risks and Benefits of Treatments: The COMPARE Study (2020)

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Type of publication:
Journal article

Author(s):
Watson V, McCartan N, Krucien N, Abu V, Ikenwilo D, Emberton M, Ahmed HU

Study involved patients at Shrewsbury and Telford Hospital NHS Trust

Citation:
Journal of Urology. 2020 Aug;204(2):273-280

Abstract:
PURPOSE: COMPARE (COMparing treatment options for ProstAte cancer) aimed to evaluate and quantify the trade-offs patients make between different aspects of active surveillance and definitive therapy.
METHODS: A Discrete Choice Experiment (DCE) tool was used to elicit patients' preferences for different treatment characteristics in 34 urology departments. Patients with localised prostate cancer completed the DCE within one week of being diagnosed and before they made treatment decisions. The DCE was pre-tested (N=5) and piloted (n=106) with patients. Patients chose their preferred treatment profile based on six characteristics: treatment type (active surveillance, focal therapy, radical therapy), return to normal activities, erectile function, urinary function, not needing more cancer treatment and 10-15 year cancer-specific survival. Different tools were designed for low-intermediate (n=468) and high-risk (n=166) patients. An error-components conditional logit model was used to estimate preferences and trade-offs between treatment characteristics.
RESULTS:Low-intermediate risk patients were willing to trade 6.99% absolute decrease in survival to have active surveillance over definitive therapy. They were willing to trade 0.75%, 0.46% and 0.19% absolute decrease in survival for a one-month reduction in time-to-return to normal activities, and 1% absolute improvements in urinary and sexual function, respectively. High-risk patients were willing to trade 3.10%, 1.04% and 0.41% absolute decrease in survival for a one-month reduction in time-to-return to normal activities and 1% absolute improvements in urinary and sexual function, respectively.
CONCLUSIONS: Patients with low-intermediate risk prostate cancer preferred active surveillance to definitive therapy. Patients of all risks were willing to trade-off cancer-specific survival for improved quality-of-life.Registration:clinicaltrials.gov Registration Identifier NCT01177865Funding:Medical Research Council (UK) (grant reference: G1002509)

CT Calcium Score In The Elderly With Aortic Stenosis (2020)

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Type of publication:
Conference abstract

Author(s):
*Pastfield E.; *Botley S.; *Pakala V.; *Ingram T.; *Lee E.

Citation:
Journal of Cardiovascular Computed Tomography; 2020; vol. 14 (no. 1)

Abstract:
Introduction: Degenerative aortic stenosis is a common condition. Many elderly frail patients with multiple comorbidities now have an alternative to conventional surgery since the availability of transcutaneous aortic valve implantation (TAVI). Echocardiography (echo) remains the key tool for the diagnosis of aortic stenosis. CT calcium scoring, has proven a useful adjunct to diagnosis, when there are discordant echo measurements. The current societies' consensus propose a cut-off score (>2000 for men and >1200 for women) above which 'severe aortic stenosis is likely'. However, many elderly patients have discordant echo measurements, low calcium score despite having severe aortic stenosis. We propose that the adverse event rates in elderly patients, regardless of calcium score category, are not significantly different. Method(s): We retrospectively examined the records of consecutive patients undergoing CT calcium score between Jan 2017 and Sep 2019. These investigations were done, either for TAVI procedure planning or as an adjunct to assessing the severity of aortic stenosis (in the case of discordant echo measurements). All these patients were followed up for adverse events, defined as a composite of heart failure, chest pain or death. Statistical analysis was performed using SPSS 25 (IBM). Result(s): 88 patients, age 82+/-6 years, 55% men, underwent CT aortic valve calcium scoring and echo. Peak aortic velocity 3.9 +/- 0.8 m/s, mean gradient 35 +/- 13 mmHg, aortic valve area 0.8 +/- 0.2cm2, stroke volume index (SVI) 38 +/- 11 ml/m2. 52.4% of the study population had discordant echo measurements and 43.6% had SVI<35ml/m2. The calcium score for women and men were 2230 +/- 1250 and 3866 +/- 1997 respectively. 24% of these patients had calcium score below the cut-off value for 'likely severe aortic stenosis'. Median follow up was 382 days (range 66-1381 days) from the initial echo. Adverse events occurred in 20+/-4% and 29+/-5% in the 'high' and 'low' calcium score groups, independent t-test, p=0.40. Using Kaplan-Meier survival curve, there is no difference in the event free survival days between the two groups, 888 days for the 'low' and 702 days for the 'high' calcium score groups, Log rank Chi-square=0.26, p=0.61. Conclusion(s): In an elderly population with aortic stenosis, there is no difference in short term adverse event rates (composite of heart failure/death/chest pain) as categorised by their calcium scores. Therefore, the current diagnostic approach may under estimate the severity of aortic stenosis in some patients. [Formula presented]

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome (2020)

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Type of publication:
Journal article

Author(s):
Jabbari E, Holland N, Chelban V, Jones PS, Lamb R, Rawlinson C, Guo T, Costantini AA, Tan MMX, Heslegrave AJ, Roncaroli F, Klein JC, Ansorge O, Allinson KSJ, Jaunmuktane Z, Holton JL, Revesz T, Warner TT, Lees AJ, Zetterberg H, Russell LL, Bocchetta M, Rohrer JD, Williams NM, Grosset DG, Burn DJ, Pavese N, Gerhard A, Kobylecki C, Leigh PN, Church A, Hu MTM, Woodside J, Houlden H, Rowe JB, Morris HR.

Patients at Shrewsbury and Telford Hospital NHS Trust were recruited into this study.

Citation:
JAMA Neurol. 2020 Mar 1;77(3):377-387.

Abstract:
IMPORTANCE:
Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied.

OBJECTIVE:
To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD.

DESIGN, SETTING, PARTICIPANTS:
This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019.

MAIN OUTCOMES AND MEASURES:
Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures.

RESULTS:
A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05).

CONCLUSIONS AND RELEVANCE:
These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.

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Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial (2020)

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Type of publication:
Randomised controlled trial

Author(s):
Fernando I.N.; Spooner D.; Latief T.N.; Stevens A.; Bowden S.J.; Herring K.; Ahmed I.; Rea D.W.; Brookes C.L.; Marshall A.; Dunn J.; Grieve R.; Poole C.J.; Churn M.; *Agrawal R.K.; Brunt A.M.; Goodman A.; Canney P.; Ritchie D.; Bishop J.

Citation:
Radiotherapy and Oncology; 2020; Vol 24; p. 52-61

Abstract:
Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity.
Method(s): SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893.
Finding(s): Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). Interpretation(s): Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF.

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The diagnostic value of cytology in parotid Warthin's tumors: international multicenter series (2020)

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Type of publication:
Journal article

Author(s):
Borsetto, Daniele; Fussey, Jonathan M; Cazzador, Diego; Smith, Joel; Ciorba, Andrea; Pelucchi, Stefano; Donà, Sara; Boscolo-Rizzo, Paolo; Tomasoni, Michele; Lombardi, Davide; Nicolai, Piero; Zanoletti, Elisabetta; Colangeli, Roberta; Emanuelli, Enzo; *Osborne, Max S; *Ahsan, Syed F; Tofanelli, Margherita; Tirelli, Giancarlo; McNamara, Katherine; Liew, Leonard; *Harrison, Katherine; Fassina, Ambrogio; Sarcognato, Samantha; Sharma, Neil; Rao, Kanishka; Pracy, Paul; Nankivell, Paul

Citation:
Head & Neck; 2020; Vol 42(3) p. 522-529

Abstract:
INTRODUCTION Warthin's tumor (WT) is a common benign salivary gland neoplasm with a negligible risk of malignant transformation. However, there is a risk of malignant tumors being misdiagnosed as WT on cytology and inappropriately managed conservatively.
METHODS Patients from nine centers in Italy and the United Kingdom undergoing parotid surgery for cytologically diagnosed WT were included in this multicenter retrospective series. Definitive histology was compared with preoperative cytological diagnoses. Surgical complications were recorded.
RESULTS A total of 496 tumors were identified. In 88.9%, the final histological diagnosis was WT. In 21 cases (4.2%) a malignant neoplasm was diagnosed, which had been incorrectly labeled as WT on cytology.
CONCLUSIONS The risk of undiagnosed malignancy should be balanced against surgical risks when considering the management of WT. Although nonsurgical management remains an appropriate option, there may be a rationale for serial clinical or radiological evaluation if surgical excision is not performed.

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An Epidemiological Study of Foot and Ankle Motocross Motorcycling Injuries in the United Kingdom (2020)

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Type of publication:
Journal article

Author(s):
*Orfanos G.; *Paavana T.; *Hill S.O.; *Singh R.A.; *Hay S.M.

Citation:
Foot and Ankle Surgery; Oct 2020; vol. 26 (no. 7); p. 797-800

Abstract:
Background: Motocross is a recreational and competitive sport involving motorcycle racing on off-road circuits. Participants have enjoyed their sport worldwide for over 100 years. In the United Kingdom, there are over 200 clubs, with over 900 events annually. Unfortunately, little evidence exists on motocross injuries and their prevention. The aim of this study is to report and to quantify the different foot and ankle injuries observed in motocross.
Method(s): Data was collected prospectively between August 2010 to August 2015 at our regional trauma unit, regardless of whether the sport was performed competitively or recreationally.
Result(s): Foot and ankle related injuries were identified in 210 patients (age range 4-78 years), with the majority being male participants (189, 90%). The majority of injuries occurred within the 21- to 30-year-old-age group. Most injuries were sustained around the start of the motocross season, in early spring and the summer months. A total of 76 patients (36%) required operative intervention. The most common injury was ankle fracture (49, 23%), followed by ankle sprain (44, 21%).
Conclusion(s): This is the first epidemiological study in the United Kingdom documenting foot and ankle injuries in motocross. The frequency and severity of motocross-related injuries is presented. This may serve to provide recommendations and guidelines in the governing bodies of this sport. The surge in motocross popularity is correlates with an increase in injuries and inevitably the resources required to treat them.
Level of Evidence: Prospective descriptive epidemiological study. Level 1.

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Management of mid-urethral tape complications: a retrospective study (2020)

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Type of publication:
Journal article

Author(s):
Offiah I.; *Rachaneni S.; Dua A.

Citation:
Journal of Obstetrics and Gynecology of India; 2020 Apr;70(2):152-157

Abstract:
Background/purpose of the study: Following mid-urethral tape insertion, for stress urinary incontinence (SUI), a proportion of women experience complications such as voiding dysfunction or tape erosion which fail to respond to conservative management approaches. These women thus require further surgical treatment. Our objective was to describe the outcomes of the surgical management of complications in these women.
Method(s): This retrospective study describes the results obtained following the surgical management of midurethral tape complications. Twenty-nine consecutive women who required mid-urethral tape lysis, loosening or excision for tape-related complications in the period 2007-2017 were included. Primary outcomes were improvement in voiding dysfunction and resolution of pain, while secondary outcomes were evaluation of the recurrence of stress urinary incontinence and patient satisfaction. Patient outcomes were measured using the Patient Global Impression of Improvement questionnaire.
Result(s): There were 1459 mid-urethral tape procedures performed in the study period. Twenty-nine women (1.99%) who had revision surgery for tape complication were identified. Interventions included tape loosening or lysis in 19 women and tape excision in ten women. Twenty-three of the 29 patients reported a significant improvement in their symptoms postoperatively. Two women had a recurrence of SUI in the tape excision cohort; all patients following tape loosening or lysis remained continent.
Conclusion(s): Tape revision surgery is a safe and effective treatment for mid-urethral tape complications with the majority of women maintaining continence following revision. Early intervention and proactive
management of complications, by the appropriate specialist, will improve outcomes.

Practice pattern variability in the management of acute severe colitis: A UK provider survey (2019)

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Type of publication:
Journal article

Author(s):
Sebastian S.; Lisle J.; Subramanian S.; Dhar A.; Shenoy A.; Limdi J.; *Butterworth J.; Allen P.B.; Samuel S.; Moran G.; Shenderey R.; Parkes G.; Raine T.; Lobo A.J.; Kennedy N.A.

Citation:
Frontline Gastroenterology; Jul 2020; vol. 11 (no. 4); p. 272-279

Abstract:
Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy. Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted. The survey evaluated provider characteristics and general practice in the setting of ASUC, followed by a vignette with linked questions.
Result(s): The response rate of the survey was 31% (209/682 IBD section members). 134 (78%) reported they would use standard infliximab dose (5 mg/kg) while 37 (22%) favoured a higher front-loading dose of 10 mg/kg citing low albumin, high C-reactive protein as their reason for their preference. IBD specialists chose the higher front-loading dose more often compared with other gastroenterologists (p=0.01) In the specific case vignette, accelerated induction (AI) was favoured by 51% of the respondents while 25% used the standard induction regime and 19% favoured colectomy. IBD specialists more often favoured AI compared with other gastroenterologists (p=0.03) with the main reason being presence of predictors of low infliximab levels (74%). The reasons cited for favouring standard induction (n=57) included lack of evidence for AI (18), their usual practice (11), unlicensed regime (7), and safety concerns (4).
Conclusion(s): There are significant variations in practice in the use of infliximab rescue therapies with an urgent need for development of care pathways to standardise practice.

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