Mikael H Sodergren's research while affiliated with Saint Mary’s Hospital and other places

Cannabis-based products for medicinal use were rescheduled in the UK in November 2018. The primary outcomes of this cross-sectional survey were to assess awareness of legislation governing these products among UK police officers and whether they had received appropriate training. 200 police officers completed the survey, and 57 (28.5%) respondents did not know these products were legal on prescription in the UK. 177 (88.5%) police officers believed they would benefit from more training on them and how to identify legal medical cannabis patients. Education on the legalities of cannabis-based products for medicinal use and why they are prescribed is necessary to improve knowledge among police officers.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a median 5 year-survival rate of 12%. Cannabidiol (CBD) has been found to exhibit antineoplastic potential and may potentiate the anticancer effects of cytotoxic’s such as gemcitabine. CBD therapy has been linked to de novo synthesis of ceramide. The sphingolipid ceramide is a potent tumour suppressor lipid with roles in apoptosis and autophagy. One of the key players involved is ceramide synthase, an enzyme with six isoforms (CerS1-CerS6), reported to have disease prognostic value. Quantitative real time PCR was used to determine mRNA expression levels of ceramide synthase isoforms, GRP78, ATF4 and CHOP. Western blotting was used to analyze protein expression of these markers and knockdown of CerS1 and GRP78 were applied via an siRNA and confirmed by the two mentioned methods. Mice with PDAC xenografts were injected via intraperitoneal method with drugs and tumours were analysed with flow cytometry and processed using H&E and IHC staining. siRNA knockdown of ceramide synthase 1 (CerS1) and analysis point to evidence of a putative CerS1 dependent pathway driven by CBD in activating endoplasmic reticulum (ER) stress target; GRP78. Upon CBD treatment, CerS1 was upregulated and downstream this led to the GRP78/ATF4/CHOP arm of the unfolded protein response (UPR) pathway being activated. In an in vivo model of PDAC in which CerS1 was not upregulated on IHC, there was no observed improvement in survival of animals, however a reduction in tumour growth was observed in combination chemotherapy and CBD group, indicating further investigations in vivo. These findings provide evidence of a potential ceramide induced cytotoxic mechanism of action of CBD in pancreatic ductal adenocarcinoma.

On 26 April 2023, past and present members of the department of surgery and cancer as well as those of wider supporting medical specialties of St Mary’s Hospital (SMH), London, congregated at the Royal Society under the headship of Professor Ara Darzi to celebrate 100 years since the establishment of an academic chair of surgery at SMH. The day also sought to recognise the global impact this institution has had on the surgical field over the past century and to look forwards to the major innovations that will shape the next. The event was divided into nine key sessions: cancer and minimally invasive surgery, vascular surgery, trauma and orthopaedic surgery, medicine’s impact on surgery, design, surgical education, artificial intelligence and digital health, patient safety, and allied technologies. In this article, we describe the founding of academic surgical units in the UK, and also present the key surgical ‘firsts’, breakthroughs and innovations realised at SMH in each of these realms. We finish with a look forwards to what the future holds for this institution and indeed the field of surgery as a whole.

BACKGROUND In 2019, it was estimated that approximately 1.4 million adults in the United Kingdom (UK) purchase illicit cannabis to self-treat chronic physical and mental health conditions. This analysis was conducted following the rescheduling of cannabis-based medicinal products (CBMPs) in the UK, but before the first specialist clinics had started treating patients. OBJECTIVE The aim of this study was to assess the prevalence of illicit cannabis consumption to treat a medically diagnosed condition, following the introduction of specialist clinics who could prescribe legal CBMPs in the UK. METHODS Adults over the age of 18 in the UK were invited to participate in a cross-sectional survey though YouGov® between 22nd and 29th September 2022. A series of questions were asked about respondents’ medical diagnoses, illicit cannabis use, cost of purchasing illicit cannabis per month, and basic demographics. The responding sample was weighted to generate a sample representative of the adult population of the UK. Modelling of population size was conducted based on an adult (≥ 18 years) population of 53,369,083 according to 2021 national census data. RESULTS There were 10,965 respondents to the questionnaire, to which weighting was applied. 5,700 (51.98%) respondents indicated that they were affected by a chronic health condition. The most reported condition was anxiety (n = 1588; 14.48%). Of those suffering with health conditions, 364 (6.38%) purchased illicit cannabis to self-treat health conditions. 1,770,627 (95% confidence interval: 1,073,791–2,467,001) individuals were modelled to consume illicit cannabis for health conditions across the United Kingdom. On multivariable logistic regression, the following were associated with increased likelihood of reporting illicit cannabis use for health reasons: chronic pain, fibromyalgia, post-traumatic stress disorder, multiple sclerosis, other mental health disorders, male gender, younger age, living in London, being unemployed or not working for other reasons, and working part-time (p<0.050). CONCLUSIONS This study highlights the scale of illicit cannabis use for health reasons in the UK and the potential barriers to accessing legally prescribed CBMPs. This is an important step in developing harm reduction policies to transition these individuals, where appropriate, to CBMPs. This is particularly true considering the potential risks from harmful contaminants of illicit cannabis and self-treating a medical condition without clinical oversight. Moreover, it emphasises the need for further funding of randomised controlled trials and the use of novel methodologies to determine the efficacy of CBMPs and their utility in common chronic conditions. CLINICALTRIAL N/A

Introduction The primary aim of this study was to assess changes in sleep‐specific health‐related quality of life (HRQoL) for those prescribed cannabis‐based medicinal products (CBMPs) for insomnia. Methods A case series of UK patients with insomnia was analyzed. Primary outcomes were changes in the Single‐Item Sleep‐Quality Scale (SQS), Generalized Anxiety Disorder‐7 (GAD‐7), and EQ‐5D‐5L at up to 6 months from baseline. Statistical significance was identified as a p value < .050. Results 61 patients were included in the analysis. There was an improvement in the SQS from baseline at 1, 3, and 6 months (p < .001). There were also improvements in the EQ‐5D‐5L Index value and GAD‐7 at 1, 3, and 6 months (p < .050). There were 28 (45.9%) adverse events recorded by 8 patients (13.1%). There were no life‐threatening/disabling adverse events. Conclusion Patients with insomnia experienced an improvement in sleep quality following the initiation of CBMPs in this medium‐term analysis. Fewer than 15% of participants reported one or more adverse events. However, due to the limitations of the study design, further investigation is required before definitive conclusions can be drawn on the efficacy of CBMPs in treating insomnia.

This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline ( P < 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (n = 184, 41.63%) and moderate (n = 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation.