University Hospital Southampton NHS Foundation Research Articles

O04 Delineation of psoriasis from uninvolved skin using an artificial neural network as a means of targeting phototherapy to psoriatic lesions

Abstract Introduction and aims Narrowband ultraviolet B therapy (NB-UVB) is an effective treatment for psoriasis. Currently, NB-UVB is delivered in whole-body cabinets to all of the patient’s skin, thus increasing the risk of normal skin sunburning and the potential risk of skin cancer development. This limits the NB-UVB doses that can be used and requires patients attend sessions three times weekly for up to 10 weeks in order to complete treatment. An artificial intelligence (AI)-mediated, targeted NB-UVB approach would avoid these risks and allow use of higher NB-UVB doses for the areas of the skin affected by psoriasis. We sought to train an artificial neural network on digital images of psoriasis, and subsequently test this trained model in order to assess its accuracy at distinguishing psoriasis from unaffected skin. Methods Overall, 104 digital images of psoriasis from 14 patients with this skin condition, who attended the dermatology department at University Hospital Southampton NHS Foundation Trust, were used to train a conditional generative adversarial network– ‘pix2pix’. Areas of psoriasis were delineated within the images prior to the images being augmented by randomly cropping, rotating and altering colour intensity, thereby increasing the total number to 23 111 images to train and test the neural network. Results The trained neural network was able to identify psoriasis in unseen digital images with 96.73% accuracy at the pixel level across the dataset. The output of the neural network (i.e. a computer-generated image of psoriasis) acted as a signal source for a digital micromirror device (DMD) that was able to shape visible light and project this light over the original image of psoriasis, while avoiding the uninvolved skin. Conclusions It is possible to differentiate psoriasis from unaffected skin within digital images using an artificial neural network. We demonstrated that AI-mediated targeted phototherapy using a DMD is feasible.

Clearing the air: Assessing healthcare professionals' awareness of air pollution's health consequences

Air pollution (AP) significantly jeopardises health, with the Royal College of Physicians accepting the adverse effects of AP are not being sufficiently communicated to patients by healthcare professionals (HCP). To explore HCPs' understanding and attitudes toward AP and its health impacts, we conducted a service evaluation survey in a group of hospital doctors.A questionnaire comprising 20 questions about AP and its health associations was completed by 133 hospital doctors working at University Hospital Southampton NHS Foundation Trust, UK.While 65% (n = 86) of respondents strongly agreed that AP is relevant to health, 79% (n = 105) felt insufficiently trained on AP and its health associations.The survey shows that HCPs' knowledge of AP and its connection to poor health is a major barrier in discussions with patients. Further research is needed to understand whether these views are nationally shared among HCPs and to explore the most effective strategies for enhancing AP awareness.

A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications

Background The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (μCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a μCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies. Methods The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients. The facility employs specialised μCT equipment explicitly designed for histology applications, allowing whole-block XRH imaging of formalin-fixed and paraffin-embedded tissue specimens. It also enables correlative imaging by combining μCT imaging with other microscopy techniques, such as immunohistochemistry (IHC) and serial block-face scanning electron microscopy, as well as data visualisation, image quantification, and bespoke analysis. Results Over the past seven years, the XRH facility has successfully completed over 120 projects in collaboration with researchers from 60 affiliations, resulting in numerous published manuscripts and conference proceedings. The facility has streamlined the μCT imaging process, improving productivity and enabling efficient acquisition of 3D datasets. Discussion & Conclusions The 3D X-ray Histology (XRH) facility at UHS is a pioneering platform in the field of histology and biomedical imaging. To the best of our knowledge, it stands out as the world's first dedicated XRH facility, encompassing every aspect of the imaging process, from user support to data generation, analysis, training, archiving, and metadata generation. This article serves as a comprehensive guide for establishing similar XRH facilities, covering key aspects of facility setup and operation. Researchers and institutions interested in developing state-of-the-art histology and imaging facilities can utilise this resource to explore new frontiers in their research and discoveries.

A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications.

The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (μCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a μCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies. The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients. The facility employs specialised μCT equipment explicitly designed for histology applications, allowing whole-block XRH imaging of formalin-fixed and paraffin-embedded tissue specimens. It also enables correlative imaging by combining μCT imaging with other microscopy techniques, such as immunohistochemistry (IHC) and serial block-face scanning electron microscopy, as well as data visualisation, image quantification, and bespoke analysis. Over the past seven years, the XRH facility has successfully completed over 120 projects in collaboration with researchers from 60 affiliations, resulting in numerous published manuscripts and conference proceedings. The facility has streamlined the μCT imaging process, improving productivity and enabling efficient acquisition of 3D datasets. The 3D X-ray Histology (XRH) facility at UHS is a pioneering platform in the field of histology and biomedical imaging. To the best of our knowledge, it stands out as the world's first dedicated XRH facility, encompassing every aspect of the imaging process, from user support to data generation, analysis, training, archiving, and metadata generation. This article serves as a comprehensive guide for establishing similar XRH facilities, covering key aspects of facility setup and operation. Researchers and institutions interested in developing state-of-the-art histology and imaging facilities can utilise this resource to explore new frontiers in their research and discoveries.

The Significance and Burden of Congenital Cytomegalovirus Infection: Interviews with Two Leading Experts

Human cytomegalovirus (CMV) is a member of the family Herpesviridae. This virus can remain dormant in the body over a long period after initial infection. Transmission of CMV occurs through direct contact with bodily fluids, such as saliva, urine, blood, semen, and breast milk, from individuals who are actively shedding the virus in these bodily fluids. CMV is extremely common and is found throughout all geographical locations and socioeconomic groups. Congenital cytomegalovirus (cCMV) infection is the most common congenital infection globally and has potentially severe consequences for infants; however, there is little awareness of cCMV infection among pregnant females, families, and healthcare professionals (HCP). For this article, EMJ conducted interviews in March 2023 with two leading experts: Christine E. Jones from the University of Southampton and University Hospital Southampton NHS Foundation Trust, UK; and Megan Pesch from the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, USA, and the National CMV Foundation, Tampa, Florida, USA, both of whom have a wealth of experience and expertise in the management of cCMV. The experts gave valuable insights into topics such as the impact of cCMV infection on infants and their families and on public health; and screening, diagnosis, and treatment of cCMV infection. The experts also explored the potential complications of cCMV, particularly sensorineural hearing loss, the importance of prevention of maternal infection, and strategies to raise awareness of cCMV infection among HCPs and the public. In addition, Pesch provided a patient advocate perspective on the consequences of cCMV infection, sharing their experience of how cCMV has impacted their child, themself, and their family.

Ldquo]Adrenal Giants[rdquo] Review of adrenal masses ≥ 10 cm detected and treated during a 10- year period at the University Hospital Southampton NHS Foundation Trust, United Kingdom

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Editorial: Lipids to support physiology and function: both quantity and quality are important

aSchool of Human Development and Health, Faculty of Medicine bNIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK cFatty Acid Research Institute dDepartment of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA Correspondence to Philip C. Calder, School of Human Development and Health, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: [email protected]

Clinical impact of syndromic molecular point-of-care testing for gastrointestinal pathogens in adults hospitalised with suspected gastroenteritis (GastroPOC): a pragmatic, open-label, randomised controlled trial

Single-occupancy isolation rooms are a finite resource in UK hospitals but are crucial in preventing transmission of infection. Patients with suspected gastroenteritis are nursed in single-occupancy rooms, but delays in laboratory testing lead to non-infectious patients remaining isolated for prolonged periods unnecessarily. Rapid molecular test panels for gastrointestinal pathogens have a run time of around 1 h but their clinical impact is unknown. We aimed to evaluate the clinical impact of syndromic molecular point-of-care testing (mPOCT) for gastrointestinal pathogens in adult patients presenting to hospital with suspected gastroenteritis on single-occupancy room use and a range of other outcome measures. In this pragmatic, open-label, randomised controlled trial, we enrolled adults hospitalised with suspected gastroenteritis in a large UK hospital. Patients were randomly allocated (1:1) to receive syndromic mPOCT of stool or rectal samples, or to routine clinical care (control) with laboratory testing. The primary outcome was the duration of time in single-occupancy rooms assessed on a modified intention-to-treat basis. Secondary outcomes included the time to results, time to de-isolation, antibiotic use, and safety outcomes. The study was registered with ISRCTN, ISRCTN88918395, and is complete. Between March 20, 2017 and March 17, 2020, from 455 patients assessed for eligibility, we enrolled 278 patients, 138 assigned to mPOCT (one withdrawal) and 140 to the control group. The duration (geometric mean) of single-occupancy room isolation was 1·8 days (95% CI 1·5-2·2) in the mPOCT group compared with 2·6 days (2·2-3·0) in the control group (exponentiated coefficient 0·70 [95% CI 0·56 to 0·87]; p=0·0017). The median (IQR) time to results was 1·7 h (1·5-2·0) for mPOCT and 44·7 h (21·2-66·1) for the control group (p<0·0001). Time to de-isolation was 0·6 days (0·3-1·8) in the mPOCT group compared with 2·2 days (1·2-3·2) in the control group, (p<0·0001). Antibiotics were given in 89 (65%) of 137 in the mPOCT group and 66 (47%) of 140 in the control group (p=0·0028). There were no differences between groups in length of hospital stay, or in safety outcomes including mortality, intensive care unit admission, or readmission to hospital. mPOCT for gastrointestinal pathogens in patients with suspected gastroenteritis returned results more rapidly than conventional testing and was associated with a reduction in single-occupancy room use. However, these benefits need to be balanced against a potential increase in antibiotic use. University Hospital Southampton NHS Foundation Trust.

Comparative genomic epidemiology of serotype 3 IPD and carriage isolates from Southampton, UK between 2005 and 2017.

Serotype 3 pneumococci remains a significant cause of disease despite its inclusion in PCV13. Whilst clonal complex 180 (CC180) represents the major clone, recent studies have refined the population structure into three clades: Iα, Iβ and II, with the last being a recent divergent and more antibiotic-resistant. We present a genomic analysis of serotype 3 isolates from paediatric carriage and all-age invasive disease, collected between 2005 and 2017 in Southampton, UK. Forty-one isolates were available for analysis. Eighteen were isolated during the annual cross-sectional surveillance of paediatric pneumococcal carriage. The remaining 23 were isolated from blood/cerebrospinal fluid specimens at the University Hospital Southampton NHS Foundation Trust laboratory. All carriage isolates were CC180 GPSC12. Greater diversity was seen with invasive pneumococcal disease (IPD) with three GPSC83 (ST1377: n=2, ST260: n=1) and one GPSC3 (ST1716). For both carriage and IPD, Clade Iα was dominant (94.4 and 73.9 % respectively). Two isolates were Clade II with one from carriage (a 34-month-old, October 2017) and one invasive isolate (49-year-old, August 2015). Four IPD isolates were outside the CC180 clade. All isolates were genotypically susceptible to penicillin, erythromycin, tetracycline, co-trimoxazole and chloramphenicol. Two isolates (one each from carriage and IPD; both CC180 GPSC12) were phenotypically resistant to erythromycin and tetracycline; the IPD isolate was also resistant to oxacillin.In the Southampton area, carriage and invasive disease associated with serotype 3 is predominantly caused by Clade Iα CC180 GPSC12.

Unexpected benefits: reflections on virtual relationship building within public involvement during the Covid-19 pandemic

The Covid-19 pandemic reduced research collaborations with public contributors and prevented face-to-face interaction. The formation of Researcher Coffee Mornings within the Wessex region aimed to continue relationships between the research community and public through the pandemic. Researcher Coffee Mornings were regular Zoom meetings run by public involvement staff at University Hospital Southampton NHS Foundation Trust, UK. They were created to provide pastoral support and ‘check-ins’ between staff and public contributors during the Covid-19 pandemic. Reorganisation, implemented by public involvement staff but led by public contributors, meant that the events evolved over time. The Researcher Coffee Mornings were a means to share updates about research with the public. They were a safe space for involvement staff, researchers and the public to exchange knowledge and share experiences. This article highlights the intended and unexpected benefits of investing in relationships. We reflect on these benefits through the perspectives of the public involvement staff, public contributors and researchers. Investing in relationships has brought value to everyone involved. By demonstrating the benefits of providing regular, inclusive spaces for relationship building between the research community and public contributors, we hope to encourage others to invest in relationship building in their settings, to improve public involvement practices.

Surgery for Ulcerative Colitis in the White British and South Asian Populations in Selected Trusts in England 2001-2020: An Absence of Disparate Care and a Need for Specialist Centres.

Over the last decade, there has been extensive evidence that patients with inflammatory bowel disease from minority communities in the UK receive less than optimal care. In none of the studies has the role of surgery in the management of acute and severe ulcerative colitis been considered in any detail. A freedom of information (FOI) request was sent to 14 NHS Trusts in England, which serve significant South Asian populations. Details of the type of surgery patients from the South Asian and White British communities received between 2021 and 2020 were requested. Detailed responses were obtained from eight Trusts. Four hundred and ten White British patients underwent surgery for ulcerative colitis over this period at these eight Trusts, together with 67 South Asian patients. There was no statistically significant difference in the distribution across the types of surgery undergone by the two communities overall (χ2 = 1.3, ns) and the proportions who underwent an ileo-anal anastomosis with pouch (z = −1.2, ns). However, within individual trusts, at the University Hospital Southampton NHS Foundation Trust, a significantly greater proportion of South Asian patients had an ileo-anal anastomosis with pouch compared to White British patients. At Cambridge University Hospitals NHS Foundation Trust, all 72 patients who underwent surgery for ulcerative colitis were White British. This study has shown that, in general, for patients with a severe flare of ulcerative colitis where medical treatment has failed and surgery is warranted, the nature of the procedures offered is the same in the White British and South Asian communities. However, of concern is the number of units with low volume procedures. For most Trusts reported in this study, the overall number of Ileo-anal pouch anastomosis or anastomosis of ileum to anus procedures performed over a number of years was substantially below that required for a single surgeon to achieve competence. These findings reinforce the argument that inflammatory bowel disease surgery should be performed in a limited number of high-volume centres rather than across a wide range of hospitals so as to ensure procedures are carried out by surgeons with sufficient and on-going experience.

Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity.

Abstract Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. To determine T cell subsets and effector molecules that drive pathogenesis of severe asthma, we performed single-cell transcriptome analysis of &amp;gt;50,000 airway CD4+ T cells isolated from bronchoalveolar lavage (BAL) samples from 30 patients with mild and severe asthma. We observed striking heterogeneity in the nature of CD4+ T cells present in asthmatics' airways with tissue-resident memory (TRM) cells making a dominant contribution. Notably, in severe asthmatics a subset of CD4+ TRM cells (CD103-expressing) was significantly increased, comprising nearly 65% of all CD4+ T cells in the airways of male patients with severe asthma when compared to mild asthma (13%). This subset was enriched for transcripts linked to T cell receptor (TCR) activation (HLA-DRB1, HLA-DPA1, CD40LG) and cytotoxicity (GZMB, GZMH), and following stimulation expressed high levels of transcripts encoding for pro-inflammatory non-TH2 cytokines (CCL3, CCL4, CCL5, TNF, LIGHT) that could fuel persistent airway inflammation and remodeling. Our findings indicate the need to look beyond the traditional T2 model of severe asthma to better understand the heterogeneity of this disease. This work was supported by (i) NIH research grant R01HL114093 (PV) and equipment grants (S10RR027366 - BD FACSAria Fusion, and S10OD025052 - Illumina Novaseq 6000); the William K. Bowes Jr. Foundation (P.V.). The WATCH study is supported by the Southampton NIHR Biomedical Research Centre and the Southampton NIHR Clinical Research Facility which are funded by the NIHR and are a partnership between the University of Southampton and University Hospital Southampton NHS Foundation Trust.

Survival Outcomes following LINAC based Stereotactic Radiosurgery/Stereotactic Radiotherapy (SRST) treatment of brain metastases: The Wessex Experience

Abstract Aims Since 2016, the University Hospital Southampton NHS Foundation Trust (UHSFT) has been commissioned by NHS England to deliver SRST to brain metastases. At UHSFT, all referrals are discussed at the Wessex Neurosciences multidisciplinary team meeting. Referrals that satisfy the criteria set by NHS England (estimated prognosis greater than 6 months, absence or controlled extracranial disease or potentially controllable extracranial disease with a Karnofsky Performance Status &amp;gt;70%) will be offered SRST. This retrospective study was performed to assess overall survival rates of patients with brain metastases treated with SRST with further tumour subtype analysis. We also benchmarked our results with other SRST centres. Method Retrospective data collection was performed for all the patients who have been treated with SRST. Patients who received SRST to a single metastasis, multiple metastases and/or to the resection cavity between 01/01/2017 to 30/09/2019 were included in this study. All treatment was delivered using a LINAC based SRST platform. Prescription doses ranged from 13.5 Gy to 21 Gy in a single fraction, 21 to 24 Gy in 3 fractions and 25 Gy in 5 fractions. Patients are treated using a stereotactic thermoplastic immobilisation shell and dynamic conformal arc therapy with ExacTrac TM and Cone Beam CT imaging. Dates of death were obtained from the NHS Digital Spine and survival analysis using median overall survival was performed using the Kaplan Meier Method. Results 277 patients were treated between 01/01/17 and 30/9/2019. The median overall survival from the Kaplan Meier Method was shown to be 14.7 months and the 6-month overall survival was 71% for all patients. Sub-group analysis of individual tumour sites showed: lung (n=110) median OS 12.1 months, melanoma (n=58) median OS 26.4 months, breast (n=46) median OS not reached (67% still alive) but 18 months survival was 70%, renal (n=22) median OS 15.4 months and colorectal (n=19) median OS 6 months. “Other” tumour sites (n=22) included patients with ovarian, neuroendocrine, sarcoma, testis, oesophagus, unknown primary and gallbladder which were grouped together due to small patient numbers. 41% of patients treated were alive at the time of analysis. Conclusion Patients with brain metastases treated with SRST at UHFST have similar outcomes compared to other SRST centres. These patients have a median overall survival of 14.7 months. However, 29% of patients analysed did not survive more than 6 months. Further collection and analysis of the data might improve patient selection and their outcomes.

Developing an intervention to optimise the outcome of cardiac surgery in people with diabetes: the OCTOPuS pilot study

BackgroundCardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to improved postoperative outcomes. The aim of this study was to develop and pilot a specialist diabetes team-led intervention to improve surgical outcomes in people with diabetes.DesignOpen pilot feasibility studySettingDiabetes and cardiothoracic surgery departments, University Hospital Southampton NHS Foundation TrustParticipantsSeventeen people with diabetes undergoing cardiothoracic surgeryInterventionFollowing two rapid literature reviews, a prototype intervention was developed based on a previously used nurse-led outpatient intervention and tested.Primary outcomeFeasibility and acceptability of delivering the interventionSecondary outcomesBiomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In depth qualitative interviews with participants and healthcare professionals were used to explore perceptions and experiences of the intervention and how it might be improved.ResultsThirteen of the 17 people recruited completed the study and underwent cardiothoracic surgery. All components of the OCTOPuS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention as a result of feedback from the participants and healthcare professionals. Median (IQR) HbA1c was 10 mmol/mol (3, 13) lower prior to surgery than at baseline.ConclusionThis study has shown that it is possible to develop a clinical pathway to improve diabetes management prior to admission. The clinical and cost-effectiveness of this intervention will now be tested in a multicentre randomised controlled trial in cardiothoracic centres across the UK.Trial registrationISRCTN; ISRCTN10170306. Registered 10 May 2018.

Elective DC cardioversion: a comparison of the carbon footprint of the care pathways for warfarin and DOAC treated patients.

Editor – What is the impact of changing anticoagulation from warfarin to direct-acting oral anticoagulants (DOAC) on the carbon footprint (CF) of the elective direct current cardioversion (EDCCV) care pathway (supplementary material S1; Fig S1)? After Integrated Research Application System (230497), institutional approval (RHM-CR10347) and patient consent, we recruited all patients presenting for EDCCV under general anesthesia at University Hospital Southampton NHS Foundation Trust (UHS) between 2012–2017. Prospectively, data from 22 patients were analysed: mode of transport to their general practitioner and UHS, anaesthesia drugs, disposables, oxygen, waste generation and time spent …

DNA methyltransferase inhibitor guadecitabine combined with cisplatin and gemcitabine chemotherapy (SPIRE): Randomized expansion phase as neoadjuvant therapy for bladder urothelial carcinoma.

447 Background: Pre-clinical data support a hypothesis that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers including urothelial carcinoma (UC). SPIRE comprised a previously reported phase Ib dose escalation phase for incurable metastatic solid cancers which established a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin (GC) chemotherapy (Crabb et al, ESMO Congress 2018, abstract 425P). We now report the SPIRE phase IIa randomised dose expansion phase which tested neoadjuvant treatment of bladder UC. Methods: Patients had T2-4a N0 M0 bladder UC intended for radical treatment. All patients received an investigator choice of 3 or 4 planned, 21-day, GC cycles (cisplatin 70 mg/m2, IV, day 8; gemcitabine 1000 mg/m2, IV, days 8 and 15). 20 patients were randomised (1:1, open label) to whether they also received guadecitabine 20 mg/m2, SC, on days 1 to 5, and G-CSF prophylaxis 300 µg, SC, on days 15 to 21. The primary objective for the expansion phase was to confirm a safe and biologically effective dose and schedule for this combination for future investigation. Circulating cell free DNA LINE-1 promotor methylation was measured as a guadecitabine pharmacodynamic endpoint. Trial registration: ISRCTN 16332228. Funding: Cancer Research UK, Astex Pharmaceuticals. Sponsor: University Hospital Southampton NHS Foundation Trust. Results: Median age was 68 (interquartile range (IQR) 59-72). 19 (95%) patients were male and 17 (85%) had T2 stage. The commonest grade ≥3 adverse events were neutropenia and thrombocytopenia with one or both affecting 6 (60%) patients in each treatment arm (no grade 5 events). One episode of neutropenic fever occurred (guadecitabine arm). Addition of guadecitabine to GC, versus GC alone, resulted in similar cisplatin dose intensity (median total doses 408 mg (IQR 384-435 mg) and 435 mg (IQR 384-435 mg) respectively) but modestly reduced gemcitabine dose intensity (median total doses 10,450 mg (IQR 9,500-11,400) and 12,768 mg (IQR 9,500-12,768) respectively). All patients completed post-chemotherapy radical treatment (8 cystectomy, 2 radiotherapy, in each arm) with similar timing post chemotherapy and peri-operative morbidity scores. LINE-1 promotor methylation depletion occurred at cycle day 8 in guadecitabine treated patients. Conclusions: Guadecitabine in combination with GC and G-CSF is safe and tolerable in this combination compared to GC alone as neoadjuvant treatment for UC. Radical surgery or radiotherapy delivery, and cisplatin dose intensity, were not compromised. Pharmacodynamic endpoints are optimal with this treatment schedule. Addition of guadecitabine to GC warrants further investigation. Clinical trial information: 16332228.

Supporting efforts for a global COVID-19 vaccine.

British Journal of NursingVol. 30, No. 1 CommentSupporting efforts for a global COVID-19 vaccineKirsty GladasKirsty GladasE-mail Address: [email protected]Lead Clinical Educator for Research, University Hospital Southampton NHS Foundation TrustSearch for more papers by this authorKirsty GladasPublished Online:12 Jan 2021https://doi.org/10.12968/bjon.2021.30.1.6AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Caddy S. Developing a vaccine for Covid-19. BMJ. 2020;369:m1790. https://doi.org/10.1136/bmj.m1790 Crossref, Medline, Google ScholarKrammer F. SARS-CoV-2 vaccines in development. Nature. 2020; 586:516–527. https://doi.org/10.1038/s41586-020-2798-3 Crossref, Medline, Google ScholarNational Institute for Health Research. CRN Wessex. 2020a. https://tinyurl.com/y8h582vh (accessed 16 December 2020 Google ScholarNational Institute for Health Research. Restart framework. 2020. https://tinyurl.com/y8r2dxeo (accessed 16 December 2020) Google ScholarUniversity Hospital Southampton. Southampton's COVID-19 vaccine trial volunteers thanked by Prime Minister. 2020. https://tinyurl.com/ycphnrfy (accessed 16 December 2020) Google Scholar FiguresReferencesRelatedDetailsCited byMeasuring the impact of the COVID-19 vaccine rolloutIan Peate18 February 2021 | Independent Nurse, Vol. 2021, No. 2 14 January 2021Volume 30Issue 1ISSN (print): 0966-0461ISSN (online): 2052-2819 Metrics History Published online 12 January 2021 Published in print 14 January 2021 Information© MA Healthcare LimitedPDF download

Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised&amp;nbsp;Non-Inferiority&amp;nbsp;Trial&amp;nbsp;Comparing&amp;nbsp;Heterologous&amp;nbsp;And Homologous&amp;nbsp;Prime-Boost Schedules with An Adenoviral Vectored and mRNA COVID-19 Vaccine

Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised&amp;nbsp;Non-Inferiority&amp;nbsp;Trial&amp;nbsp;Comparing&amp;nbsp;Heterologous&amp;nbsp;And Homologous&amp;nbsp;Prime-Boost Schedules with An Adenoviral Vectored and mRNA COVID-19 Vaccine

Improving the care of patients with acute kidney injury.

Becky Bonfield, Lead Advanced Nurse Practitioner, University Hospital Southampton NHS Foundation Trust (Becky.Bonfield@uhs.nhs.uk), runner-up in the Renal Nurse of the Year category in the BJN Awards 2020.

Variation in UK guidelines for the first-line antimicrobial management of paediatric orbital cellulitis-time for national recommendations.

Stimes GT, Girotto JE. Applying pharmacodynamics and antimicrobial stewardship to pediatric preseptal and orbital cellulitis. Paediatr Drugs. 2019;21:427–38. Article Google Scholar Georgakopoulos CD, Eliopoulou MI, Stasinos S, Exarchou A, Pharmakakis N, Varvarigou A. Periorbital and orbital cellulitis: a 10-year review of hospitalised children. Eur J Ophthalmol. 2010;20:1066–72. Article Google Scholar Tsirouki T, Dastiridou AI, Ibanez Flores N, Castellar Cerpa J, Moschos MM, Brazitikos P, et al. Orbital cellulitis. Surv Ophthalmol. 2018;63:543–53. Article Google Scholar Amin N, Syed I, Osborne S. Assessment and management of orbital cellulitis. Br J Hosp Med. 2016;77:216–20. Article Google Scholar Wong SJ, Levi J. Management of pediatric orbital cellulitis: a systematic review. Int J Pediatr Otorhinolaryngol. 2018;110:123–9. Article Google Scholar Markham JL, Hall M, Bettenhausen JL, Myers AL, Puls HT, McCulloh RJ. 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The authors declare that they have no conflict of interest. Publisher’s note Springer...