Staff Publication

The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam (2023)

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Type of publication:
Journal article

Author(s):
Kumar A; Quraishi MN; Al-Hassi HO; El-Asrag ME; Segal JP; Jain M; Steed H; Butterworth J; Farmer A; Mclaughlin J; Beggs A; Brookes MJ Authors Full Name Kumar, Aditi; Quraishi, Mohammed Nabil; Al-Hassi, Hafid O; El-Asrag, Mohammed E; Segal, Jonathan P; Jain, Manushri; Steed, Helen; *Butterworth, Jeffrey; Farmer, Adam; Mclaughlin, John; Beggs, Andrew; Brookes, Matthew

Citation:
Frontiers in Microbiology. 14:1134105, 2023. [epub ahead of print]

Abstract:
Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. alpha-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial alpha/beta-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.

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Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity (2023)

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Type of publication:
Journal article

Author(s):
Fernando IN; Lax S; Bowden SJ; Ahmed I; Steven JH; Churn M; Brunt AM; *Agrawal RK; Canney P; Stevens A; Rea DW Authors Full Name Fernando, I N; Lax, S; Bowden, S J; Ahmed, I; Steven, J H; Churn, M; Brunt, A M; Agrawal, R K; Canney, P; Stevens, A; Rea, D W.

Citation:
Clinical Oncology (Royal College of Radiologists). Volume 35, pages 397-407, 2023 Mar 20.

Abstract:
AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (>=85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

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Frontal fibrosing alopecia in men: is it any different?. (2022)

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Type of publication:
Conference abstract

Author(s):
*Jacob M.A.; *Jain D.; *Shaw R.;

Citation:
British Journal of Dermatology. Conference: 102nd Annual Meeting of the British Association of Dermatologists. Glasgow United Kingdom. 187(Supplement 1) (pp 100), 2022. Date of Publication: July 2022.

Abstract:
Frontal fibrosing alopecia (FFA) is a scarring disease characterized by a receding frontotemporal hairline associated with varying degrees of eyebrow alopecia. It is usually seen in postmenopausal women. FFA has occasionally been reported in men, and can be confused with androgenetic alopecia, and therefore present quite late to the clinician. Although, histopathologically, FFA is similar in both sexes, there are a few differences clinically and with regard to treatment. We aimed to highlight these characteristics. A 51-year-old male presented with hair loss of 3 years' duration involving the eyebrows, sideburns and beard, followed by frontotemporal recession of the hairline. He reported a similar history in his mother and maternal aunt. In addition, he was known to have testosterone deficiency with low levels of total and free testosterone and sex hormone binding globulin, and was on replacement therapy. His remaining serology, including thyroid profile, was within normal limits. Clinical examination showed patchy alopecia of the eyebrows, eyelashes, sideburns and beard. There was frontotemporal recession of hairline along with loss of follicular orifices and perifollicular erythema. Additionally, he had diffuse thinning of the hair over the vertex and nonscarring alopecia over his extremities. A punch biopsy showed end-stage scarring alopecia with perifollicular fibrosis and 'backing off' of the surrounding lichenoid inflammatory infiltrate consistent with lichen planopilaris. A clinical diagnosis of FFA was made and the patient was started on hydroxychloroquine tablets along with 1% topical pimecrolimus twice daily over the patches of alopecia on the face. Common sites of hair loss in men include the sideburns, beard, eyebrows, eyelashes and occipital hair, and facial hair loss may precede eyebrow loss, as was the case in our patient. Facial papules, androgenetic alopecia and loss of body hair are more often observed in men with FFA than in women. In addition, the loss of body hair and eyelashes and the presence of facial papules have been associated with more severe forms of FFA and can be used as a prognostic indicator. Autoimmune conditions like thyroid disease and lichen planus are uncommon in males, although androgen deficiency has been linked to FFA in males in various studies. In addition, hormone-blocking drugs can contribute to FFA. Therefore, it is very important to keep this in mind during history and examination and perform relevant blood tests. In addition, treatment with minoxidil may provide better results in males.

A case of BASCULE (Bier anaemic spots associated with cyanosis and urticaria-like eruption) syndrome associated with postural hypotension. (2022)

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Type of publication:
Conference abstract

Author(s):
*Shaw, Roberta; *Oliwieckim Simone

Citation:
British Journal of Dermatology. Conference: 102nd Annual Meeting of the British Association of Dermatologists. Glasgow United Kingdom. 187(Supplement 1) (pp 206), 2022. Date of Publication: July 2022.

Abstract:
A 15-year-old boy presented to the paediatric dermatology clinic with an unusual bilateral intermittent rash to his lower legs, which he had noticed for many years. The patient demonstrated multiple irregular white macules and urticated papules on a background of cyanosis of the legs when standing for prolonged periods, such as in the shower, and which was relieved by sitting. The mother believed that the rash began after a flu-like illness, and aside from this he was usually fit and well, with no significant past medical history, family history or regular medications. The patient had a full blood screen, including coagulation screen, which were normal. The patient described an intermittent lightheaded sensation on standing. Therefore, while in clinic the patient had a lying and standing blood pressure, which demonstrated a significant systolic drop from 137 mmHg lying to 109 mmHg standing, while his heart rate remained stable. The clinical findings suggested a diagnosis of BASCULE syndrome. BASCULE syndrome is a benign vasomotor dermatosis first described in 2016. The clinical findings described include Bier anaemic spots, cyanosis and urticaria-like eruption. The pathogenic mechanism remains unknown but is thought to be associated with transient tissue hypoxia through arteriolar vasoconstriction causing a paradoxical urticated rash that is worse on standing. Although BASCULE syndrome has been described as a separate entity, there have been links to POTS (postural orthostatic tachycardia syndrome) and orthostatic acrocyanosis, and so these diagnoses should be considered when investigating a patient with similar features.

Addressing patients' concerns in speech and language therapy consultations following the diagnosis and treatment of head and neck cancer (2023)

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Type of publication:
Journal article

Author(s):
*Zuydam, Annette C; Rogers, Simon N; Roe, Justin W G.

Citation:
Current Opinion in Otolaryngology and Head and Neck Surgery. 2023 Volume: 31 Issue 3

Abstract:
PURPOSE OF REVIEW: Head and neck cancer (HNC) and its treatment impacts profoundly on patients' functional abilities, emotional well being and social interactions. Communication and swallowing are fundamental to everyday life, and the Speech and Language Therapist (SLT) has a critical role for both patients and their carers. In clinical practice, patient-reported outcome measures (PROMs) are a key part of the armamentarium of the SLT. The purpose of the review is to summarize how these measures can be beneficial in the context of time pressured SLT outpatient consultations. RECENT FINDINGS: Unmet needs in HNC are common and impact negatively on quality of life. There is an ever-increasing number of articles in this area, and it can be a challenge to identify, distil and summarize those specific to SLT. SUMMARY: In this review, we discuss the scope of holistic evaluation, strengths and limitations of PROMs, the Patient Concerns Inventory-Head and Neck, barriers to the use of outcome measures, the carers perspective and surveillance. SLT are uniquely placed members of the multidisciplinary team and provide expert advice and intervention. The inclusion of PROMs in routine consultations provides a model of follow up, which helps address patients and carers complex and unmet needs, ultimately promoting better outcomes.

An Assessment of Factors That Influence Outcome Following Fixation of Periprosthetic Distal Femur Fractures Associated with Total Knee Arthroplasty (2022)

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Type of publication:
Journal article

Author(s):
*Fakoya, Keji; *Sedarous, Ramy; *Seifo, Mina; *Okoro, Tosan

Citation:
Ortopedia Traumatologia Rehabilitacja. 24(3):193-199, 2022 Jun 30.

Abstract:
BACKGROUND: Periprosthetic distal femur fractures following total knee arthroplasty (PDFFTKA) are increasingly common [1], mainly in elderly patients with significant co-morbidities [2]. Surgical management usually requires balancing prompt fixation for early mobilization with the need to consider the least physiologically demanding option [3]. The aim of this study was to assess predictors of clinical and radiological outcome in patients with PDFFTKA treated with open reduction and internal fixation (ORIF). MATERIALS AND METHODS: A retrospective cohort study of patients managed for PDFFTKA over the last 21 years in the Trauma & Orthopaedics Department of the Royal Shrewsbury Hospital (RSH) was carried out. Radiological images, pre- and post-operatively, were assessed for fracture related parameters. Last known functional status was evaluated using the most recent outpatient review letters. After assessment of normality of data, evaluation of predictors of clinical and radiological outcome was made using correlation analyses. RESULTS: There was no statistically significant correlation between age, primary TKA to fracture interval, and length of intact medial cortex vs clinical outcome for the parametric variables evaluated. For non-parametric variables assessed, there was a statistically significant correlation between clinical outcome and evidence of callus formation (Spearman rho value -0.476; p=0.022). In stratifying the patients with poor and good outcome, there was no difference noted in primary TKA to fracture interval, or length of intact medial cortex (mm) between both groups. In terms of the number of comminuted fragments and anterior flange to fracture distance (mm), there was also no difference noted between the poor and good functional groups. CONCLUSIONS: 1. There was no observed correlation in pre-operative patient and fracture related variables with outcome in this population of patients with PDFFTKA. 2. Post-operative evidence of callus formation appears to be directly related to better clinical outcomes.

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A Pilot Study on the Effect of Colesevelam on the Microbiome in Primary Terminal Ileal Resected Crohn's Disease (2023)

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Type of publication:
Conference abstract

Author(s):
Kumar A.; Quraishi M.N.; Al-Hassi H.O.; Elasrag M.; Segal J.P.; Jain M.; Steed H.; *Butterworth J.; Farmer A.; McLaughlin J.; Beggs A.; Brookes M.

Citation:
Journal of Crohn's and Colitis. Conference: 18th Congress of European Crohn's and Colitis Organisation, ECCO 2023. Copenhagen Denmark. 17(Supplement 1) (pp i532), 2023. Date of Publication: February 2023

Abstract:
Background: Surgery plays a pivotal role in ileal Crohn's disease despite the risk of endoscopic recurrence following an ileocaecal resection greater than 65% within 12 months of surgery. More than 90% of Crohn's patients have a concomitant diagnosis of bile acid diarrhoea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in post-operative Crohn's patients with bile acid diarrhoea can alter the microbiome and prevent disease recurrence. Method(s): Post-operative Crohn's patients with symptoms of diarrhoea underwent 75SeHCAT testing for bile acid diarrhoea. If positive (75SeHCAT < 15%), patients were treated with colesevelam and stool samples were collected at 4-weeks, 8-weeks and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in clinic as per local guidelines. Patients underwent a 6-12 months post-operative colonoscopy where mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeerts score < i2 and disease recurrence 3 i2. Faecal and mucosal 16S ribosomal RNA gene analysis was undertaken to assess a/b-diversity and microbial composition. Result(s): A total of 44 faecal samples and 44 mucosal biopsies were sequenced from 14 patients. 1/10 patients on colesevelam and 2/4 patients not on colesevelam demonstrated disease recurrence. There was no significant difference in a/b-diversity pre- and post-treatment. Pre-treatment, the three most abundant bacterial classes in all patients were Bacteroidia, Clostridia and Gammaproteobacteria (Figure 1). Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the two patients not given colesevelam, 1/2 (50%) showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. Conclusion(s): This small pilot study demonstrated that patients who were given colesevelam, a bile acid sequestrant, were more likely to be in disease remission at their 6-12 months colonoscopy review. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in post-operative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance.

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High BMI at breast cancer diagnosis associated with significantly more metastatic disease, and increased likelihood of death from breast cancer recurrence (2023)

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Type of publication:
Conference abstract

Author(s):
*Lake, Blossom; Damery, Sarah; *Wilson, Mandy; *Appleton, Donna; Jolly, Kate

Citation:
European Journal of Surgical Oncology, February 2023, Volume 49(2), pages E87-E88

Abstract:
Background: 50% of patients with breast cancer are overweight or obese, with the West Midlands having second highest rate of obesity in the UK. Elevated BMI has been associated with breast cancer recurrence. This study looked at recurrence in Shropshire breast cancer survivors.

The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK (2023)

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Type of publication:
Journal article

Author(s):
Okoth, Kelvin; *Parry Smith, William; Thomas, G Neil; Nirantharakumar, Krishnarajah; Adderley, Nicola J

Citation:
BMC Medicine, 2023, 21, Article number: 104

Abstract:
Background
Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk.

Methods
A UK retrospective cohort study (1995–2021) using data from a nationwide database (The Health Improvement Network). Women aged 18–40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls.

Results
During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00–1.19), IHD 1.18 (1.01–1.37), cerebrovascular disease 1.04 (0.92–1.17), HF 1.30 (1.02–1.65), hypertension 1.07 (1.03–1.11), T2DM 1.37 (1.29–1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02–1.52), IHD 1.13 (0.81–1.57), cerebrovascular disease 1.43 (1.10–1.87), HF 0.99 (0.57–1.75), hypertension 1.31 (1.21–1.43), T2DM 1.74 (1.52–1.98).

Conclusions
History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.

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