Author: Jason Curtis

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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Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cohort study (2023)

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Type of publication:
Journal article

Author(s):
Mantaka A; Gatselis N; Triantos CK; *Thalheimer U; Leandro G; Zachou K; Konstantakis C; Saitis A; Thomopoulos K; Kouroumalis EA; Dalekos GN; Samonakis DN

Citation:
Minerva gastroenterology. 69(1):107-113, 2023 Mar.

Abstract:
BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used.

RESULTS: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not  statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047).

CONCLUSIONS: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

The Perils of Riding Motocross: A Summary of this Extensive, Prospective Study (2023)

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Type of publication:Journal article

Author(s):Hay B; *Singh R; Hay S

Citation:Indian Journal of Orthopaedics. 1-6, 2023 Feb 07

Abstract:Background: Motocross is a high-risk form of motorbiking where serious injuries occur regularly, although little data have been collected to illustrate this relationship. Over 5 years, teams from RJAH Oswestry and RSH sought to demonstrate the impact of Motocross on orthopaedic presentation and workload. Method: Data were collected prospectively over 5 years including 615 orthopaedic injuries associated with both recreational and competitive motocross. Results: An increase in injury and operation frequency was observed, young males were identified as the highest risk participant. This was evident over winter and weekends, during the competitive racing season. A variety of injuries have been implicated, some with life threatening or disabling consequences. Conclusion: Motocross has seen exponential growth in popularity with increases in injuries and operations. This implicates major impacts on finances and healthcare, especially at times of seasonal vulnerability. The authors encourage event organisers to explore the avenues of rider safety in this increasingly popular sport.

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