Adoption of routine surgical video recording: a nationwide freedom of information act request across England and Wales.

Background: Surgical video contains data with significant potential to improve surgical outcome assessment, quality assurance, education, and research. Current utilisation of surgical video recording is unknown and related policies/governance structures are unclear. Methods: A nationwide Freedom of Information (FOI) request concerning surgical video recording, technology, consent, access, and governance was sent to all acute National Health Service (NHS) trusts/boards in England/Wales between 20th February and 20th March 2023. Findings: 140/144 (97.2%) trusts/boards in England/Wales responded to the FOI request. Surgical procedures were routinely recorded in 22 trusts/boards. The median estimate of consultant surgeons routinely recording their procedures was 20%. Surgical video was stored on internal systems (n = 27), third-party products (n = 29), and both (n = 9). 32/140 (22.9%) trusts/boards ask for consent to record procedures as part of routine care. Consent for recording included non-clinical purposes in 55/140 (39.3%) trusts/boards. Policies for surgeon/patient access to surgical video were available in 48/140 (34.3%) and 32/140 (22.9%) trusts/boards, respectively. Surgical video was used for non-clinical purposes in 64/140 (45.7%) trusts/boards. Governance policies covering surgical video recording, use, and/or storage were available from 59/140 (42.1%) trusts/boards. Interpretation: There is significant heterogeneity in surgical video recording practices in England and Wales. A minority of trusts/boards routinely record surgical procedures, with large variation in recording/storage practices indicating scope for NHS-wide coordination. Revision of surgical video consent, accessibility, and governance policies should be prioritised by trusts/boards to protect key stakeholders. Increased availability of surgical video is essential for patients and surgeons to maximally benefit from the ongoing digital transformation of surgery. Funding: KL is supported by an NIHR Academic Clinical Fellowship and acknowledges infrastructure support for this research from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC).

The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K).

The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders as they are key components in regulating cell signalling pathways. In an effort to make probe molecules available for further exploring these targets, we have previously reported PI5P4Kα-selective and PI5P4Kγ-selective ligands. Herein we report the rational design of PI5P4Kα/γ dual inhibitors, using knowledge gained during the development of selective inhibitors for these proteins. ARUK2007145 (39) is disclosed as a potent, cell-active probe molecule with ADMET properties amenable to conducting experiments in cells.

Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.

The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) play a central role in regulating cell signalling pathways and, as such, have become therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders. Many of the PI5P4Kα inhibitors that have been reported to date have suffered from poor selectivity and/or potency and the availability of better tool molecules would facilitate biological exploration. Herein we report a novel PI5P4Kα inhibitor chemotype that was identified through virtual screening. The series was optimised to deliver ARUK2002821 (36), a potent PI5P4Kα inhibitor (pIC50 = 8.0) which is selective vs. other PI5P4K isoforms and has broad selectivity against lipid and protein kinases. ADMET and target engagement data are provided for this tool molecule and others in the series, as well as an X-ray structure of 36 solved in complex with its PI5P4Kα target.

Glaucoma Drainage Device Surgery Outcomes in Children With Uveitic Glaucoma.

PURPOSE: To evaluate outcomes of glaucoma drainage device (GDD) implantation children with uveitic glaucoma. DESIGN: Retrospective interventional case series. METHODS: Success was defined as intraocular pressure (IOP) ≥5 and ≤21 mm Hg. Failure was defined at final follow-up when the IOP was outside the success criterion, and visual function was no perception of light or if further glaucoma surgery (excluding removal of intraluminal stent suture or needling) was required. RESULTS: Fifty eyes of 36 children with uveitic glaucoma underwent GDD implantation. Mean age at surgery was 10.1±3.1 years (range 5-17) with a mean follow-up of 113±61 months (range 8-228). Mean cumulative probabilities of success (95% CI) were 0.98 (0.86-1.00) at 1 year, 0.87 (0.73-0.94) at 5 years, and 0.59 (0.32-0.78) at 15 years. Fourteen tubes were classified as failed, with 12 due to uncontrolled IOP (11 eyes required a second GDD); 1 eye, removal of the tube due to plate exposure; and 1 eye, lost light perception. Postoperative complications occurred in 36% of patients and included hypotony (22%), tube exposure (6%), tube obstruction (4%), corneal decompensation (2%), and cystoid macular edema (2%). Visual acuity remained stable (preoperation 0.35±0.42 vs postoperation 0.45±0.67, P = .49). IOP was significantly reduced from 31.4±7.5 mm Hg to 14.4±5.1 mm Hg (P < .0001) as were the number of glaucoma medications 3.5±1.0 vs 1.1±1.3 (P < .0001). CONCLUSIONS: Refractory pediatric uveitic glaucoma can be treated successfully by GDD implantation. Further interventions to manage consequences of glaucoma or the underlying disease are common, and visual function is maintained in the majority of cases.

The Identification of Potent, Selective, and Brain Penetrant PI5P4Kγ Inhibitors as In Vivo-Ready Tool Molecules.

Owing to their central role in regulating cell signaling pathways, the phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive therapeutic targets in diseases such as cancer, neurodegeneration, and immunological disorders. Until now, tool molecules for these kinases have been either limited in potency or isoform selectivity, which has hampered further investigation of biology and drug development. Herein we describe the virtual screening workflow which identified a series of thienylpyrimidines as PI5P4Kγ-selective inhibitors, as well as the medicinal chemistry optimization of this chemotype, to provide potent and selective tool molecules for further use. In vivo pharmacokinetics data are presented for exemplar tool molecules, along with an X-ray structure for ARUK2001607 (15) in complex with PI5P4Kγ, along with its selectivity data against >150 kinases and a Cerep safety panel.

Effect of trabeculectomy on the rate of progression of visual field damage.

OBJECTIVES: This study quantifies the effect of trabeculectomy on the rate of progression (RoP) of visual field (VF) damage utilising pre- and post-operative visual function as the outcome instead of surrogate outcomes of success. METHODS: Clinical and VF data from 199 sequential patients who underwent trabeculectomy between 2015 and 2016 were extracted from the network of sites of Moorfields Eye Hospital NHS Foundation Trust. Of these, we analysed 80 eyes of 74 patients who met our inclusion criteria of at least three reliable VFs before and after surgery (false positive rate <15%). The change in mean RoP (dB/year) was tested using point-wise sensitivity values through a mixed effect model with random effects on both intercepts and slopes. A broken-stick regression of sensitivity over time, with a breakpoint at the day of surgery, modelled the individual change in RoP. RESULTS: We analysed 10 [9,12] VFs per subject (Median [Interquartile Range]). At surgery, the age was 67 [57, 72] years, mean deviation was -10.84 [-14.7, -5.6] dB and the IOP was 18 [15, 20] mmHg. One year after surgery, the IOP was 10 [8,13] mmHg (p = 0.002). Mean RoP before surgery was -0.94 [-1.20, -0.69] dB/year (Mean [95% credible intervals]) and it was slowed down by 0.62 [0.26, 0.97] dB/year (p < 0.001) after surgery. CONCLUSIONS: Trabeculectomy leads to a significant reduction in the RoP of VF loss postoperatively.

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.

Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunological disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochemical properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kß. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chemical series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.

A picture of health: determining the core population served by an urban NHS hospital trust and understanding the key health needs.

BACKGROUND: NHS hospitals do not have clearly defined geographic populations to whom they provide care, with patients able to attend any hospital. Identifying a core population for a hospital trust, particularly those in urban areas where there are multiple providers and high population churn, is essential to understanding local key health needs especially given the move to integrated care systems. This can enable effective planning and delivery of preventive interventions and community engagement, rather than simply treating those presenting to services. In this article we describe a practical method for identifying a hospital's catchment population based on where potential patients are most likely to reside, and describe that population's size, demographic and social profile, and the key health needs. METHODS: A 30% proportional flow method was used to identify a catchment population using an acute hospital trust in West London as an example. Records of all hospital attendances between 1st April 2017 and 31st March 2018 were analysed using Hospital Episode Statistics. Any Lower Layer Super Output Areas where 30% or more of residents who attended any hospital for care did so at the example trust were assigned to the catchment area. Publicly available local and national datasets were then applied to identify and describe the population's key health needs. RESULTS: A catchment comprising 617,709 people, of an equal gender-split (50.4% male) and predominantly working age (15 to 64 years) population was identified. Thirty nine point six percent of residents identified as being from Black and Minority Ethnic (BAME) groups, a similar proportion that reported being born abroad, with over 85 languages spoken. Health indicators were estimated, including: a healthy life expectancy difference of over twenty years; bowel cancer screening coverage of 48.8%; chlamydia diagnosis rates of 2,136 per 100,000; prevalence of visible dental decay among five-year-olds of 27.9%. CONCLUSIONS: We define a blueprint by which a catchment can be defined for a hospital trust and demonstrate the value a hospital-view of the local population could provide in understanding local health needs and enabling population-level health improvement interventions. While an individual approach allows tailoring to local context and need, there could be an efficiency saving were such public health information made routinely and regularly available for every NHS hospital.

May Measurement Month 2019: an analysis of blood pressure screening results in the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2019 (MMM19) blood pressure (BP) measurement campaign to raise awareness of hypertension especially in those who are not aware of their condition. The MMM19 standard protocol designed by the International Society of Hypertension was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken two to three times, using an automated BP apparatus and were inputted either in the MMM19 app or data were recorded in paper form and manually transferred to Excel spreadsheets by encoders supervised by the PSH. A total of 89 941 participated through opportunistic convenience sampling. After multiple imputation, a total of 47 925 (53.3%) participants had hypertension (≥140/90 mmHg or on antihypertensive medication). Of this number, 31 151 (65%) were aware that they had high BP and 30 120 (62.8%) were on antihypertensive medications. Of the 30 120 participants on antihypertensive medications, only 18 373 (61.1%) had controlled BP (<140/90 mmHg). Being overweight or obese were significant predictors of high BP. Other predictors of high systolic BP and diastolic BP were alcohol intake, smoking, and a previous history of hypertension in pregnancy, while pregnant participants had significantly lower BP. The MMM19 campaign succeeded in raising awareness of high BP in our country, and the opportunistic sampling enhanced a sense of people empowerment by their knowing how easy it is to detect high BP and thereby enabling the prevention of long-term health complications. The higher BP control in the MMM19 hypertensive individuals possibly attests to the success of the previous MMM17 and MMM18 campaigns.

Impact of the COVID-19 Pandemic on Emergency Adult Surgical Patients and Surgical Services: An International Multi-center Cohort Study and Department Survey.

OBJECTIVES: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. BACKGROUND: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. METHODS: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. RESULTS: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. CONCLUSION: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.

May Measurement Month 2019: an analysis of blood pressure screening results from Nigeria.

The aim of this study is to estimate the frequency of undetected hypertension across the six geopolitical zones of Nigeria. We conducted an opportunistic screening of adults aged at least 18 years in the month of May 2019. Participants were recruited by trained volunteers using the May Measurement Month protocol. Blood pressure (BP) was measured using validated digital and mercury sphygmomanometers. We defined hypertension as BP ≥140/90 mmHg or the use of BP-lowering medication. A total of 3646 participants (52.8% females) with a mean age of 44.5 ± 15.7 years were screened. Hypertension was present in 39.2% of the participants but only 55. 4% of these were on antihypertensive medications. Only 46.8% hypertensives who were on medications had their BP controlled (<140/90 mmHg). Previous history of hypertension in pregnancy, alcohol intake and smoking were associated with increased mean systolic and diastolic BPs. The frequency of Nigerians with hypertension is high while only about half of those on antihypertensive medications are controlled. A multi-pronged approach to reduce the burden of hypertension is needed.

May Measurement Month 2019: an analysis of blood pressure screening results from Venezuela, Latin America.

Cardiovascular diseases are the main cause of death in Venezuela. Raised blood pressure (BP) accompanied by diabetes mellitus, obesity, lipid abnormalities, and tobacco usage are the biggest contributors to mortality. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. MMM2019 included 24 672 subjects (mean age: 54.7 years, SD 25.2, 63.1% female). The proportion with hypertension was 48.9%; 14.3% were unknown hypertensives, 35.5% of those who receiving treatment had uncontrolled hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg); when considering all hypertensives, 53.3% were controlled. Sixty per cent of those on anti-hypertensive medication were on monotherapy, 27.7% were on two, and 7.7% were on three or more drugs. Body mass index, calculated for the total population, was on average 25.6 (SD: 4.8) kg/m2. 16.2% of participants were classified as obese, 34.0% as overweight, and 4.0% were classified as underweight. Diabetes mellitus was reported by 9.4%, smoking by 7.3%, and 10.5% reported drinking alcohol regularly. Conditions associated with higher BP levels were obesity, diabetes mellitus, and women with a history of hypertension during a previous pregnancy. These results are consistent with the two previous MMM campaigns and indicate that repeated screening can routinely identify hypertension. There is an urgent need for Venezuela to implement programmes of detection, treatment, and control not only for hypertension but also for other common cardiovascular risk factors.

Uptake and accessibility of surgical robotics in England.

BACKGROUND: The distribution, utilisation and accessibility of surgical robotics in England is unknown. METHODS: A nationwide Freedom of Information (FOI) request was sent to all acute National Health Service (NHS) trusts. Accessibility was assessed for 32 843 Lower Super Output Areas in England. RESULTS: All 149 acute NHS trusts responded to the FOI request. Sixty-one robots are distributed between 48 trusts. The number of robots and robotic procedures has increased annually. Urological procedures comprise 84.2% of robotic procedures. Procedure volume varies between robotic centres ranging from 1 to 683 in 2018. Over 2.4 million people have a travel time of over 1 hour to their nearest robotic centre. DISCUSSION: National accessibility to robotic services and case volumes are variable and does not represent good value for the NHS. A national robotic surgery registry could improve the quality of robotic surgery and is needed to dynamically assess national provision of this technology.

Coordinated assembly and release of adhesions builds apical junctional belts during de novo polarisation of an epithelial tube.

Using the zebrafish neural tube as a model, we uncover the in vivo mechanisms allowing the generation of two opposing apical epithelial surfaces within the centre of an initially unpolarised, solid organ. We show that Mpp5a and Rab11a play a dual role in coordinating the generation of ipsilateral junctional belts whilst simultaneously releasing contralateral adhesions across the centre of the tissue. We show that Mpp5a- and Rab11a-mediated resolution of cell-cell adhesions are both necessary for midline lumen opening and contribute to later maintenance of epithelial organisation. We propose that these roles for both Mpp5a and Rab11a operate through the transmembrane protein Crumbs. In light of a recent conflicting publication, we also clarify that the junction-remodelling role of Mpp5a is not specific to dividing cells.

New geographic model of care to manage the post-COVID-19 elective surgery aftershock in England: a retrospective observational study.

OBJECTIVES: The suspension of elective surgery during the COVID-19 pandemic is unprecedented and has resulted in record volumes of patients waiting for operations. Novel approaches that maximise capacity and efficiency of surgical care are urgently required. This study applies Markov multiscale community detection (MMCD), an unsupervised graph-based clustering framework, to identify new surgical care models based on pooled waiting-lists delivered across an expanded network of surgical providers. DESIGN: Retrospective observational study using Hospital Episode Statistics. SETTING: Public and private hospitals providing surgical care to National Health Service (NHS) patients in England. PARTICIPANTS: All adult patients resident in England undergoing NHS-funded planned surgical procedures between 1 April 2017 and 31 March 2018. MAIN OUTCOME MEASURES: The identification of the most common planned surgical procedures in England (high-volume procedures (HVP)) and proportion of low, medium and high-risk patients undergoing each HVP. The mapping of hospitals providing surgical care onto optimised groupings based on patient usage data. RESULTS: A total of 7 811 891 planned operations were identified in 4 284 925 adults during the 1-year period of our study. The 28 most common surgical procedures accounted for a combined 3 907 474 operations (50.0% of the total). 2 412 613 (61.7%) of these most common procedures involved 'low risk' patients. Patients travelled an average of 11.3 km for these procedures. Based on the data, MMCD partitioned England into 45, 16 and 7 mutually exclusive and collectively exhaustive natural surgical communities of increasing coarseness. The coarser partitions into 16 and seven surgical communities were shown to be associated with balanced supply and demand for surgical care within communities. CONCLUSIONS: Pooled waiting-lists for low-risk elective procedures and patients across integrated, expanded natural surgical community networks have the potential to increase efficiency by innovatively flexing existing supply to better match demand.

Insights from a global snapshot of the change in elective colorectal practice due to the COVID-19 pandemic.

BACKGROUND: There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation. OBJECTIVE: To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for behaviour change. DESIGN: An online survey of colorectal cancer service change globally in May and June 2020. PARTICIPANTS: Attending or consultant surgeons involved in the care of patients with colorectal cancer. MAIN OUTCOME MEASURES: Changes in the delivery of diagnostics (diagnostic endoscopy), imaging for staging, therapeutics and surgical technique in the management of colorectal cancer. Predictors of change included increased hospital bed stress, critical care bed stress, mortality and world region. RESULTS: 191 responses were included from surgeons in 159 centers across 46 countries, demonstrating widespread service reduction with global variation. Diagnostic endoscopy was reduced in 93% of responses, even with low hospital stress and mortality; whilst rising critical care bed stress triggered complete cessation (p = 0.02). Availability of CT and MRI fell by 40-41%, with MRI significantly reduced with high hospital stress. Neoadjuvant therapy use in rectal cancer changed in 48% of responses, where centers which had ceased surgery increased its use (62 vs 30%, p = 0.04) as did those with extended delays to surgery (p<0.001). High hospital and critical care bed stresses were associated with surgeons forming more stomas (p<0.04), using more experienced operators (p<0.003) and decreased laparoscopy use (critical care bed stress only, p<0.001). Patients were also more actively prioritized for resection, with increased importance of co-morbidities and ICU need. CONCLUSIONS: The COVID-19 pandemic was associated with severe restrictions in the availability of colorectal cancer services on a global scale, with significant variation in behaviours which cannot be fully accounted for by hospital burden or mortality.