2023

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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Global impact of COVID-19 pandemic on gastric cancer patients (2023)

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Type of publication:
Journal article

Author(s):
Herrera-Kok J.H.; Parmar C.; Bangash A.H.; Samadov E.; Demirli Atici S.; Cheruvu C.V.; Abouelazayem M.; Yang W.; Galanis M.; Di Maggio F.; Isik A.; *Bandopyadaya S.; Viswanath Y.K.

Citation:
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. (no pagination), 2023. Date of Publication: 02 Mar 2023.[epub ahead of print]

Abstract:

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Intussusception of the appendix in a young adult: an important differential diagnosis of abdominal pain in cystic fibrosis patients? (2023)

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Type of publication:
Journal article

Author(s):
*Venkatasami, Meena; *Cobby, Ellen.

Citation:
Journal of Surgical Case Reports. 2023(3):117, 2023 Mar.

Abstract:
Cystic fibrosis (CF) is commonly associated with gastrointestinal manifestations from infancy to adulthood. Distal intestinal obstruction syndrome (DIOS) affects 20% of CF patients, where intussusception can be a rare complication. A 20-year-old CF male was diagnosed with a 3-day history of right iliac fossa pain and diarrhoea. Clinical examination revealed a tender palpable mass in the right iliac fossa and raised serum inflammatory markers. Contrast computerized-tomography of the abdomen-pelvis suggested intussusception of the appendix and further confirmed on histological analyses. The patient underwent an open appendicectomy where the intussusception had self-resolved. The literature review indicated a scarcity of data with 10 cases reported of intussusception in adult CF patients. Our case was in line with previous research of transient intussusception. This rare case highlights an importance to carry a higher index of suspicion for gastrointestinal manifestations in CF patients where differential diagnoses of DIOS and intussusception should be considered in the acute presentation.

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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, p.159-164

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.

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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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Development and validation of a multivariable risk factor questionnaire to detect oesophageal cancer in 2-week wait patients (2023)

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Type of publication:
Journal article

Author(s):
Ho KMA; Rosenfeld A; Hogan Á; McBain H; Duku M; Wolfson PB; Wilson A; Cheung SM; Hennelly L; Macabodbod L; Graham DG; Sehgal V; Banerjee A; Lovat LB; SPIT Study Group Collaborators,. Included *Butterworth, J and *Button, H from Shrewsbury and Telford Hospital Trust as investigators

Citation:
Clinics and Research in Hepatology and Gastroenterology, 2023 Mar; Vol. 47 (3), pp. 102087

Abstract:
Introduction: Oesophageal cancer is associated with poor health outcomes. Upper GI (UGI) endoscopy is the gold standard for diagnosis but is associated with patient discomfort and low yield for cancer. We used a machine learning approach to create a model which predicted oesophageal cancer based on questionnaire responses. Methods: We used data from 2 separate prospective cross-sectional studies: the Saliva to Predict risk of disease using Transcriptomics and epigenetics (SPIT) study and predicting Risk of disease using detailed Questionnaires (RISQ) study. We recruited patients from National Health Service (NHS) suspected cancer pathways as well as patients with known cancer. We identified patient characteristics and questionnaire responses which were most associated with the development of oesophageal cancer. Using the SPIT dataset, we trained seven different machine learning models, selecting the best area under the receiver operator curve (AUC) to create our final model. We further applied a cost function to maximise cancer detection. We then independently validated the model using the RISQ dataset. Results: 807 patients were included in model training and testing, split in a 70:30 ratio. 294 patients were included in model validation. The best model during training was regularised logistic regression using 17 features (median AUC: 0.81, interquartile range (IQR): 0.69-0.85). For testing and validation datasets, the model achieved an AUC of 0.71 (95% CI: 0.61-0.81) and 0.92 (95% CI: 0.88-0.96) respectively. At a set cut off, our model achieved a sensitivity of 97.6% and specificity of 59.1%. We additionally piloted the model in 12 patients with gastric cancer; 9/12 (75%) of patients were correctly classified. Conclusions: We have developed and validated a risk stratification tool using a questionnaire approach. This could aid prioritising patients at high risk of having oesophageal cancer for endoscopy. Our tool could help address endoscopic backlogs caused by the COVID-19 pandemic.

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