Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder (FGID) characterized by intermittent episodes of nausea and vomiting. Our aim was to report its prevalence and associated features.Methods: Data concerning demographics, symptoms, and psychiatric comorbidity were collected. Symptoms compatible with CVS were classified as per Rome III criteria. We recorded whether a diagnosis of CVS was considered in patients after negative investigation. We compared demographics and association with other FGIDs in patients with and without CVS.Key Results: 920 of 1002 patients provided data. Of the 920 patients, 112 (12.2%) had symptoms compatible with CVS. Thirteen (11.6%) of these had an organic cause for their symptoms, but 99 patients (88.4%) were deemed to have CVS (prevalence=10.8%). Organic causes for symptoms compatible with CVS included gastroparesis, large hiatus hernia, achalasia, and small bowel obstruction. Only 39.4% of patients with CVS were asked about vomiting symptoms at their initial consultation, and a diagnosis of CVS was considered in only four (4.0%) of the 99 patients. CVS was associated with younger age, tobacco smoking, never having married, psychiatric comorbidity, and presence of symptoms compatible with other FGIDs (P≤.01).Conclusions and Inferences: Prevalence of CVS in this outpatient gastroenterology adult population was 10.8%. Identified associations included younger age, tobacco smoking, psychiatric comorbidity, and symptoms compatible with other FGIDs. The condition was considered as a possible diagnosis in <5% of patients who met the diagnostic criteria.

Aims/hypothesis: Individuals with type 1 diabetes are at increased cardiovascular risk, particularly in the presence of insulin resistance. A prothrombotic environment is believed to contribute to this risk but thrombotic pathways in type 1 diabetes are only partially understood and the role of platelets is incompletely studied. We hypothesised that platelets from individuals with type 1 diabetes exhibit platelet hyperactivity due to both increased propensity for activation and diminished sensitivity to inhibition, with an amplified maladaptive phenotype in those with insulin resistance. Methods: Blood samples were obtained from individuals with type 1 diabetes enrolled on the ‘Double diabEtes and adVErse cLinical Outcome: identification of mechanistic Pathways’ (DEVELOP) study with insulin resistance assessed as estimated glucose disposal rate (eGDR), whereby eGDR >8 or <6 mg kg⁻¹ min⁻¹ indicates normal insulin sensitivity or advanced insulin resistance, respectively. Platelet function was analysed using whole blood multiparameter flow cytometry to simultaneously measure three distinct markers of activation, including integrin α_IIbβ₃ (PAC-1 binding), P-selectin (CD62P) and phosphatidylserine (PS) (Annexin V). Both activation and inhibition responses of the platelets were investigated, which were subjected to the machine learning tool Full Annotation Shape-constrained Trees (FAUST) to characterise platelet subpopulations. Results: A total of 32 individuals with type 1 diabetes were studied (median age [range] of 24 [18–34] years, 59% male, diabetes duration [mean ± SD] of 14.0 ± 6.3 years and HbA_1c of 65.3 ± 14.0 mmol/mol [8.1%]). An increased basal expression, measured as mean fluorescence intensity, of all three platelet activation markers was detected in the type 1 diabetes group compared with healthy control participants (CD62P expression 521 ± 246 vs 335 ± 67; p<0.001, PAC-1 370 ± 165 vs 231 ± 88; p=0.011 and PS 869 ± 762 vs 294 ± 109; p=0.001). Following platelet stimulation, an enhanced activation of these markers was found in the type 1 diabetes group. Within the type 1 diabetes group, those with advanced insulin resistance (eGDR8 mg kg⁻¹ min⁻¹) with single agonist stimulation CD62P expression (29,167 ± 2177 vs 22,829 ± 2535, p<0.001 and PAC-1 19,339 ± 11,749 and 5187 ± 2872, p=0.02). Moreover, individuals with type 1 diabetes showed reduced sensitivity to platelet inhibition by prostacyclin (PGI₂) compared with control participants. Stratification of individuals with type 1 diabetes by insulin resistance demonstrated that in the presence of PGI₂, suppression of stimulated CD62P was 17 ± 11% and 33 ± 12% (p=0.02) for advanced insulin resistance and normal insulin sensitivity groups, respectively, with even larger differences demonstrated for PAC-1 (48 ± 17% and 75 ± 7%; p=0.006) and PS exposure (33 ± 12% and 84 ± 10%; p=0.001). Furthermore, FAUST analysis showed that, under basal conditions, there was a different distribution of the eight platelet subpopulations comparing advanced insulin resistance and normal insulin sensitivity groups, with differences also detected following PGI₂ inhibition. Conclusions/interpretation: Our novel characterisation of platelets in type 1 diabetes shows a maladaptive phenotype with increased basal activity together with hyperactivation following stimulation and diminished responses to inhibition. Insulin resistance appears to further drive this adverse thrombotic phenotype, suggesting an enhanced platelet-driven cardiovascular risk in those with type 1 diabetes and reduced insulin sensitivity. Graphical

Cardiovascular complications remain the leading cause of morbidity and mortality in individuals with diabetes, driven by interlinked metabolic, inflammatory, and thrombotic changes. Hyperglycaemia, insulin resistance/deficiency, dyslipidaemia, and associated oxidative stress have been linked to abnormal platelet function leading to hyperactivity, and thus increasing vascular thrombotic risk. However, emerging evidence suggests platelets also contribute to low-grade inflammation and additionally possess the ability to interact with circulating immune cells, further driving vascular thrombo-inflammatory pathways. This narrative review highlights the role of platelets in inflammatory and immune processes beyond typical thrombotic effects and the impact these mechanisms have on cardiovascular disease in diabetes. We discuss pathways for platelet-induced inflammation and how platelet reprogramming in diabetes contributes to the high cardiovascular risk that characterises this population. Fully understanding the mechanistic pathways for platelet-induced vascular pathology will allow for the development of more effective management strategies that deal with the causes rather than the consequences of platelet function abnormalities in diabetes.

Introduction: Primary hyperaldosteronism (PA) can affect up to 10% of patients with hypertension. Adrenal vein sampling (AVS) is used to distinguish between unilateral and bilateral aldosterone production. However, it is invasive, technically challenging and is only performed in a limited number of centres. This audit aimed to evaluate the effectiveness of AVS in informing the management of PA in a large teaching hospital. Methods: A retrospective audit of all AVS (n=38) performed in LTHT from 2011 to 2020 was conducted. Half of the cases were excluded due to limited access to data from regional referrals. Data collected included patients’ age at time of sampling, biochemistry, radiological and histological findings and outcomes following AVS. Results: Of the 19 patients who underwent AVS, the average age at time of sampling was 54.5 and 12 (63%) were males. All patients had hypertension and 16 (84%) had >1 episode of hypokalaemia. 15 (79%) patients had radiological evidence of unilateral disease. 8 (42%) patients underwent a saline infusion test prior which demonstrated failure to suppress aldosterone secretion. AVS was unsuccessful in 8 (42%) patients due to failure in cannulating the right adrenal vein. Lateralisation was demonstrated in 7 (64%) patients, of which 6 (86%) were concordant with radiology. Following AVS, 11 (58%) patients underwent unilateral adrenalectomy. Hypokalaemia resolved in all patients (9) following surgery and 9 patients (82%) had reduction in the number of antihypertensive medications. Histology demonstrated unilateral adenoma consistent with Conn’s tumour in majority (80%) of the cases. AVS results informed decisions regarding conservative or surgical management in 13 (68%) patients. Conclusion: Despite failure due to technical difficulty in a significant proportion of cases, AVS remained useful in informing the management of patients with PA. The vast majority of patients following successful AVS and subsequent surgery had positive outcomes and concordant histology.