The Princess Alexandra Hospital NHS Trust
Recent publications
Abstract: Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6 i), abemaciclib, palbociclib, and ribociclib, have been FDA-approved for the treatment of hormone receptor-positive (HR+), HER2−negative (HER2−) advanced breast cancer (aBC). This targeted therapy has revived hope in those aBC patients who did not respond to standard therapies. Interestingly, when administered as a single agent, CDK4/6 modulated several peripheral blood cells after a short-course treatment of 28 days. However, the impact of these immune effects has yet to be thoroughly investigated. Methods: We administered abemaciclib, palbociclib, and ribociclib monotherapy to 23 patients with HR+/HER2− metastatic breast cancer. The aim is to investigate the impact of on-treatment modifications on peripheral blood cells and their composite scores in patients after a 28-day course of CDK4/6 i alone. Results: In the current study, we observed a significant decrease in neutrophils (p-value < 0.001) for patients treated with abemaciclib, palbociclib, and ribociclib. An overall decrease of Tregs was observed and potentially linked to palbociclib treatment. The neutrophile to lymphocyte (N/L) ratio was also decreased overall and potentially linked to abemaciclib and palbociclib treatment. Platelets were decreased in patients administered with abemaciclib. Notably, the radiometabolic response was available only for those patients treated with ribociclib and abemaciclib, and only those lesions treated with ribociclib reached statistical relevance. Conclusions: Our study strongly supports the notion that CDK4/6 inhibitors induce tumour immune modulation. N/L ratio and platelet levels decreased due to treatment. Future studies should test whether patients would benefit from immunomodulators in association with CDK4/6 agents in a larger clinical trial. Moreover, the CDK4/6-induced immune modulation could also be considered a potential predictive clinical factor in HR+/HER2− advanced breast cancer.
Objective: To estimate the incidence and postoperative mortality rates of surgery, and variations by age, diabetes, KRT modality and time over a 15-year period. Background: Patients with kidney failure receiving chronic kidney replacement therapy (KRT; dialysis or kidney transplantation) have increased risks of postoperative mortality and morbidity. Contemporary data on the incidence and types of surgery these patients undergo are lacking. Methods: This bi-national population cohort study evaluated all incident and prevalent patients receiving chronic KRT using linked data between Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admission datasets between 2000 and 2015. Patients were categorised by their KRT modality (Hemodialysis [HD], Peritoneal Dialysis [PD], Home Hemodialysis [HHD] and Kidney transplant) for each calendar year. Incidence rates for overall surgery and subtypes were estimated using Poisson models. Logistic regression was used to estimate 30-day/in-hospital mortality risk. Results: Overall, 46,497 patients over a median [IQR] follow-up 6.3years [3.5 - 10.2] underwent 81,332 surgeries. The median incidence rate of surgery remained stable over this period with a median of 14.9 surgeries per 100-patient years. Annual incidence rate was higher in older people and those with diabetes mellitus. Patients receiving HD had a higher incidence rate of surgery compared to kidney transplant recipients (15.8 vs. 10.0 surgeries per 100-patient years, respectively). Overall adjusted postoperative mortality rates decreased by more than 70% over the study period, and were lowest in kidney transplant recipients (1.7%, 95% CI, 1.4-2.0). Postoperative mortality following emergency surgery was more than 3-fold higher than elective surgery (8.4% vs. 2.3%, respectively). Conclusions: Patients receiving chronic KRT have high rates of surgery and morbidity. Further research into strategies to mitigate perioperative risk remain a priority.
In recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody–drug conjugates consisting of a target-specific monoclonal antibody covalently linked to a payload (cytotoxic agent) is a novel and promising therapeutic strategy. In December 2019, the US Food and Drug Administration (FDA) granted accelerated approval to the nectin-4-targeting antibody–drug conjugate, enfortumab vedotin, for the treatment of advanced or metastatic urothelial carcinomas that are refractory to both immune checkpoint inhibitors and platinum-based treatment. Heavily pre-treated urothelial cancer patients reported a significant, 40% response to enfortumab vedotin while other antibody–drug conjugates are currently still under investigation in several clinical trials. We have comprehensively reviewed the available treatment strategies for advanced urothelial carcinoma and outlined the mechanism of action of antibody–drug conjugate agents, their clinical applications, resistance mechanisms and future strategies for urothelial cancer.
Objective To determine the effect of intensive care unit (ICU) length of stay (LOS) on hospital mortality and non-home discharge (NHD) for patients undergoing cardiac surgery over a 16-year period in Australia and New Zealand. Design Retrospective, multicentre, cohort study covering the time period 1 January 2004 to 31 December 2019. Setting One-hundred-and-one hospitals in Australia and New Zealand who submit data to the Australia New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD). Participants Adult patients (age over 18) who underwent coronary artery bypass grafting, valve surgery or combined valve/coronary surgery. Interventions None. Measurements and Main Results We analysed 252,948 cardiac surgical admissions from 101 hospitals with a median age of 68.3 years (interquartile range 60-75.5), of which 74.2% (187,632 of 252,948) were males. A U-shaped relationship was observed between ICU LOS and hospital mortality, with significantly elevated mortality at short (< 20 hours) and long (>5 days) ICU LOS which persisted after adjustment for illness severity and across clinically important subgroups (odds ratio for mortality with ICU LOS>5days= 3.21, 95% confidence interval 2.88-3.58, p<0.001). Conclusions Prolonged duration of ICU LOS after cardiac surgery is associated with increased hospital mortality in a U-shaped relationship. ICU LOS >5 days should be considered as a meaningful definition for prolonged ICU stay after cardiac surgery.
Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial.
IntroductionAs with most medicines historically, clinicians prescribing tildrakizumab have relied on information derived from registration studies undertaken in a prospective controlled clinical trial setting. More recently, clinicians, policymakers, and commissioners increasingly rely on real-world data to inform both policy and practice.MethodsA retrospective real-world data study was undertaken at four specialist dermatology departments in the United Kingdom. All adult patients treated with tildrakizumab for moderate-to-severe plaque psoriasis were included, with data being collected for 122 patients.ResultsPsoriatic patients on tildrakizumab tended to be overweight (median body mass index of 32 (range 19–59) (n = 61); 26/68 (38%) < 90 kg, 32/68 (47%) between 90 and 120 kg, and 10/68 (15%) > 120 kg). The study population had high levels of comorbidities (83/116, 72%), multiple special sites (39/117, 33%), and histories of biological treatments (81/100, 81%). Most patients (61/80, 76%) initiated on tildrakizumab were switched from another biological treatment. Tildrakizumab was effective, with 91/122 (75%) patients remaining on treatment for the duration of the study—a median of 12 months per patient (range 1–29 months)—and achieving a change in median Psoriasis Area and Severity Index (PASI) from 12 to 0.35 and in Dermatology Life Quality Index (DLQI) from 20 to 0. The response rate was 57/66 (86%) when tildrakizumab was used as the first- or second-line biologic compared to 19/31 (61%) when used as the third- to seventh-line. Thirty-three (78.6%) patients over 90 kg of weight received the 200-mg dose of tildrakizumab. All but one (n = 8) patient with body weight over 120 kg maintained response over time. There was one treatment discontinuation; a patient who had a local sensitivity reaction.Conclusions In UK clinical practice, tildrakizumab was well tolerated and effective at doses of 100 mg or 200 mg in a range of patient phenotypes.
Background: To explore the use of a thermoreversible copolymer gel coating to prevent donor tissue scrolling in Descemet's membrane endothelial keratoplasty (DMEK). Methods: PLGA-PEG-PLGA triblock copolymer was synthesised via ring opening polymerisation. Two formulations were fabricated and gelation properties characterized using rheological analyses. Endothelial cytotoxicity of the copolymer was assessed using a Trypan Blue exclusion assay. Thickness of the copolymer gel coating on the endothelial surface was analysed using anterior segment optical coherence tomography (OCT) (RTVue-100, Optovue Inc., California, USA). Gold nanoparticles were added to the copolymer to aid visualization using OCT. Prevention of Descemet membrane donor scrolling was represented via a novel, in vitro, immersion of copolymer coated donor graft material. Results: Two different formulations of PLGA-PEG-PLGA copolymer were successfully fabricated and the desired peak gelling temperature of 24°C was achieved by polymer blending. Application of 20%, 30% and 40% (w/v) polymer concentrations resulted in a statistically significant increase in polymer thickness on the endothelium (p<0.001). There was no detectable endothelial cytotoxicity. The polymer was easy to apply to the endothelium and prevented scrolling of the DMEK graft. Conclusion: This PLGA-PEG-PLGA thermoreversible copolymer gel could be exploited as a therapeutic aid for preventing DMEK graft scrolling.
Background: Hypersomnias of central origin (HOCO) are diverse in origin and symptomatology and remain poorly described in an Australian population. We hypothesized that the rate of human leukocyte antigen (HLA) DQB1*0602 positivity in the Australian cohort would be comparable to international registries. Aims: This study aims to evaluate epidemiological and clinical characteristics of Australian patients with HOCO, including prevalence of HLA DQB1*0602 positivity, the most specific HLA marker associated with narcolepsy. Methods: This is a retrospective study. Patients ≥ 16 years of age presenting with symptoms of hypersomnolence who attended one of 2 Australian sleep centres (New South Wales and Queensland), in the preceding 24 months, and had undergone both HLA serology and mean sleep latency tests (MSLT) were included. Main outcome measures included demographics, HLA DQB1*0602 positivity, MSLT, and clinical parameters (presence of auxiliary narcolepsy symptoms, laboratory tests, relevant prescribed medications). Results: Eighty-eight patients were included. HLA DQB1*0602 positivity was highest in those with type 1 narcolepsy (NT1) (95.7%), and lowest in those without a classifiable disorder (9.1%). Mean sleep latency was lowest and number of sleep onset rapid eye movement periods (SOREMPs) highest in the NT1 group. Comorbid disorders, particularly depression and overweight/obesity, were prevalent in all cohorts. Across all diagnostic groups, dexamphetamine was the most commonly prescribed agent for excessive daytime sleepiness. Conclusions: Patients with hypersomnias of central origin assessed in 2 specialised Australian clinics demonstrate comparable clinical characteristics to other published cohorts internationally, however available pharmacological agents in Australia do not reflect international standards of care. This article is protected by copyright. All rights reserved.
Objectives : To clinically validate a recently proposed classification scheme of post-traumatic bone defects. Methods and Materials : Open fractures were classified utilising a newly introduced classification system. This classification system is based on plain radiographs, assessing the extent and local geometry of bone loss, including: D1 - Incomplete Defects; D2 - Minor/Sub-Critical (Complete) Defects (<2 cm); and D3 - Segmental/Critical Sized Defects (≥2 cm). Reliability was assessed among six independent assessors (three trauma orthopaedic surgeons and three orthopaedic training surgeons) using Fleiss’ kappa tests. 43 open fractures from a tertiary referral trauma centre and their radiographic series were analysed. Results : Interobserver reliability testing demonstrated the proposed classification system had substantial agreement between the 6 observers, κ = 0.623 (z = 33.8), p < 0.001. Intraobserver variability showed a range of substantial to almost perfect agreement of each observer following a three-week interval between repeat assessments, κ range 0.69-0.914, p <0.001. Conclusions : In this representative validation cohort there was substantial agreement between observers when assessing a diverse range of bone defects following long bone open trauma, with highly reproducible assessments by both orthopaedic surgeons and trainee orthopaedic surgeons alike on an internal level. The classification scheme is based on conventional orthogonal radiographs and requires no sophisticated technology, and is therefore pragmatic and applicable to secondary, tertiary and quaternary levels of care for trauma patients. Level of Evidence : III
Current computed tomography (CT) shielding practices are largely based on calculations of scattered radiation emitted from an acrylic head or body phantom, such as the Computed Tomography Dose Index (CTDI) phantom, or anthropomorphic phantoms of these two anatomical categories. This report considers the difference in scattered air kerma or dose from phantom models, to actual patient scatter under a variety of clinical scan conditions. Empirical patient scatter measurements recorded at different positions around the gantry, for 3 different CT scanners, resulted in average patient scatter fractions per unit Dose Length Product (DLP: mGy cm) at 1 m from the isocentre of 0.09 ± 0.03 and 0.17 ± 0.04 µGy (mGy cm)−1 for head and body scans respectively. For the purposes of shielding design and scattered dose estimates to staff it is recommended that a single standard deviation be applied to these averages in the continued interest of conservatism. These values are reasonably comparative to the widely published scatter fractions by the National Council of Radiological Protection using the CTDI phantom, and the British Institute of Radiology using head and body anthropomorphic phantoms.
Background: Coronavirus disease 2019 (COVID-19) has posed significant challenges to the provision of elective and emergency general surgical care. Patterns of presentation have changed and management pathways have also been adapted, moving to more non-operative management (NOM) for some conditions. We investigated how COVID-19 changed the volume of emergency general surgery operating in our district general hospital (DGH). We aimed to evaluate the impact of NOM on outcomes in acute appendicitis. Methods: A retrospective case review of operating lists, patient handover lists, and patient notes was undertaken for patients presented between 1st January 2020 and 3rd June 2020. The study period was divided into two, with the period between 1st January 2020 and 23rd March 2020 representing the pre-COVID cohort. Results: Some 393 emergency general surgery operations were performed in the study period. There was a clear reduction in operating volume after 23rd March 2020. During that same period, 325 patients were assessed with right iliac fossa (RIF) pain. Median age was 21 (range 5-87) and 201 patients were female (61.8%). The rate of NOM for suspected acute appendicitis was 8.8% in the pre-COVID group, which increased to 36.4% in the COVID group. The incidence of normal histology following appendicectomy did not change with this difference in management (16.1% compared to 17.9%, p = 0.78). Conclusions: This study summarizes the changes brought to the provision of emergency general surgery in the setting of a DGH by the COVID-19 pandemic. In particular, NOM was the preferred option for acute appendicitis but this did not alter the negative appendicectomy rate.
Background Non-Surgical Facial Aesthetics (NSFA) encompasses a range of minimally invasive procedures. Complications associated with NSFA often present to local Emergency Departments. There is no representation of NSFA in the undergraduate curriculum. Medical students appear to have little to no exposure to NSFA during their training.The main aims of this study were to gain an insight into the views of final year medical students in pursuing a career in NSFA and assessing their understanding of NSFA competence and complications of common procedures. Method ology: An online survey was completed by 148 medical students across two English Universities. 106/148 (71.6%) of students were from University A and 42/148 (28.4%) were from University B. Results 47.6% (70/148) of medical students would consider pursuing a career in NSFA after graduating from medical school. 76.3% (87/148) and 80.7% (92/148) of students were not aware of the complications associated with the administration of dermal fillers and Botox injections respectively. Most medical students felt a single day training program in NSFA was sufficient to administer non-surgical rhinoplasty 67.8% (99/148) dermal fillers 67.1% (98/148) and Botox injections 68.5% (100/148). Conclusion Despite a large proportion of medical students considering a career in NSFA the majority were unaware of the common complications. Incorporation of NSFA into undergraduate curriculum should improve enhance patient safety, effective management of complications and augment future learning and career progression. This may be achieved by through signposting, student-selected components and as part of structured head and neck teaching.
Aims The Royal College of Paediatrics and Child Health (RCPCH) identified that often Paediatricians of all grades have limited time, often none, for research. This can have far-reaching consequences for the field, including a reduced understanding of research processes that patients may be involved with. The East of England (EoE) deanery is also aware of this issue. We aimed to establish a regional paediatric trainee-led research network (TRN) to enable trainees working at any of the geographically widespread sites in EoE (figure 1) to access research opportunities. This abstract summarises the work done by Paediatric trainees towards this goal. Methods A poll in July 2021 was used to understand the need for a regional Paediatric trainee research network. We also had early input from the RCPCH TRN task and finish group through the EoE representative. Following this, a group of nine enthusiastic trainees joined efforts in July 2021 towards establishing a paediatric TRN in EOE which was named CHEERI (Child Health East of England Research initiative).We created a timeline detailing specific outputs such as gaining stakeholder interest and creating a webspace which would act as a research directory for the region. We conducted meetings with academic leads such as the Head of Paediatrics, Cambridge University; and with the training programme directors. We updated trainees regularly during virtual regional study days which are well-attended. Proformas were sent to all 17 hospitals in the region, feedback from these were used in the development of a virtual research directory, within a website managed by CHEERI. Results 100% of trainees attending a regional Paediatrics meeting surveyed in July 2021 agreed a research network is needed. The CHEERI committee was established through discussing the initiative at a regional study day. It comprises nine trainees (two with academic roles) working at five Trusts, one medical student representative, and two consultant mentors.The RCPCH TRN meetings were helpful especially with guidance from other established regional TRNs, when discussing CHEERI development strategies. Completed proformas and online searches revealed six hospitals with thirty-six active Paediatric non-commercial research projects within the EoE. Five clinical paediatricians have agreed to be voluntary mentors to support trainees develop research goals. Funding used in previous face-to-face meetings were redirected towards developing the CHEERI website. We also launched a Twitter handle: @CHEERI. Challenges faced by CHEERI include lengthy response time to email communications, and lack of protected time for website and research development. Targets developed through committee discussions to launch regional or local trainee-led, consultant-directed scale-able projects. To unite existing resources and national networks, host regional events and workshops to connect research-active consultants with trainees interested in research. • Download figure • Open in new tab • Download powerpoint Abstract 814 Figure 1 Conclusion CHEERI is strongly supported by the RCPCH, EoE academic and clinical training leads. We are a group of mainly clinical trainees with consultant mentorship. We recognise the challenges faced in creating a research network. Ongoing work will include establishing a research project, gaining publications and securing funding for ongoing website and research training purposes. Regions interested in establishing their own similar research networks should contact the RCPCH TRN (https://www.rcpch.ac.uk/resources/rcpch-trainee-research-network).
Aims We surveyed Paediatric trainees in the East of England Deanery to identify the rates of breastfeeding within Paediatricians; the age at which trainees continue to breastfeed until, and to identify any barriers that trainees have in continuing to breastfeed when returning to work, with a view to addressing these issues and improve the support new mothers have in returning to work. Methods Paediatric Trainees across the East of England were surveyed in March and April 2021. The online survey was sent to all trainees in the East of England Deanery via official (deanery-initiated) emails, and unofficially with announcements at regional training events, and links sent via social media. Completion of the survey was entirely voluntary, and all participants demonstrated consent by proceeding with the survey after the consent page on the survey. The survey comprised single best choice/multiple choice/free text question. All trainees were asked to respond irrespective of their gender and experience of breastfeeding. Results Breastfeeding rates amongst Paediatric Trainees in the East of England far exceed that of the national average (97.6% initiated breastfeeding compared to the national average of 81%, with 50% breastfeeding past 12 months of age – compared to the national average of 0.5% at 12 months). 54.5% breastfeeding trainees are still breastfeeding on their return to work, and 22.3% trainees expressed on their return to work. Despite this, 29.5% all mothers surveyed stated that they stopped breastfeeding sooner than they wished as a direct result of returning to work (figure 1). This figure rose to 39.3% for those mothers that continued to breastfeed until within two months of returning to work.For those mothers that express on return to work, infants receive breast milk to an average age of 18.4 months. This compares to an average age of 16.6 months for those mothers that breastfed but did not express at work. Despite this, 34.6% mothers that expressed at work stated that they stopped breastfeeding sooner than anticipated as a direct result of work and 60% women who intentionally gave up breastfeeding stated that they stopped sooner than they anticipated as a direct result of returning to work. The most cited work-related reasons for stopping breastfeeding were long, busy shifts and night shifts (48%); inadequate expressing facilities in the workplace (38%) and a lack of protected time to express (25%). • Download figure • Open in new tab • Download powerpoint Abstract 594 Figure 1 • Download figure • Open in new tab • Download powerpoint Abstract 594 Figure 2 Conclusion The RCPCH has committed to actively promote and support breastfeeding in their facilities, events and organisation, and it is imperative that the staff members working as part of child healthcare, are also actively supported.Returning to work is a major factor in the early cessation for breastfeeding amongst Paediatric trainees, as is a perception that returning to work is not conducive to continuing to breastfeed. Better support for breastfeeding mothers, both in terms of provision of information prior to return, and changes to the workplace should be considered to help the RCPCH achieve its aim to actively support its staff in continuing to breastfeed their own children.
Background Kidney transplant recipients are at increased risk of keratinocyte cancers, namely squamous cell and basal cell carcinomas (SCCs and BCCs). This is primarily due to the high levels of immunosuppression that are required to prevent allograft rejection. Different immunosuppressive medications confer different risks, and the effect of mycophenolate mofetil on SCC and BCC risk is unclear. We explored the relationship between mycophenolate dose prescribed over the entire transplant period and the risk of SCC and BCC. Methods Kidney transplant recipients from Queensland, Australia, were recruited between 2012 and 2014 and followed until mid-2016. During this time transplant recipients underwent regular skin examinations to diagnose incident SCCs and BCCs. Immunosuppressive medication regimens were obtained from hospital records, and the average mycophenolate dose/day over the entire transplantation period was calculated for each patient. Doses were divided into three ranked groups, and adjusted relative risks (RRadj) of developing SCC and BCC tumours were calculated using negative binomial regression with the lowest dosage group as reference. Recipients who had used azathioprine previously were excluded; further sub-group analysis was performed for other immunosuppressant medications. Results There were 134 kidney transplant recipients included in the study. The average age was 55, 31% were female and 69% were male. At the highest median mycophenolate dose of 1818 mg/day the SCC risk doubled (RRadj 2.22, 95% CI 1.03–4.77) when compared to the reference group of 1038 mg/day. An increased risk persisted after accounting for ever-use of ciclosporin, ever-use of tacrolimus, and when excluding mammalian target of rapamycin users. This increased risk was mainly carried by kidney transplant recipients immunosuppressed for five or more years (RRadj = 11.05 95% CI 2.50–48.81). In contrast, there was no significant association between BCC incidence and therapy with the highest compared with the lowest mycophenolate dosage (RRadj = 1.27 95% CI 0.56–2.87). Conclusion Higher mycophenolate dosage is associated with increased SCCs in kidney transplant recipients, particularly those immunosuppressed for more than five years. The increased SCC risk persists after accounting for usage of other immunosuppressant medications.
Oxidative stress has been implicated in many diseases, including reproductive and pregnancy disorders, from subfertility to maternal vascular disease or preterm labour. There is, however, discrepancy within the standardized markers of oxidative stress in obstetrics and gynaecology in clinical studies. This review aims to present the scope of markers used between 2012 and 2022 to describe oxidative stress with regard to reproduction, pregnancy, and pregnancy-related issues. Despite the abundance of evidence, there is no consensus on the set of standardised markers of oxidative stress which poses a challenge to achieve universal consensus in order to appropriately triangulate the results.
Introduction A negative appendicectomy rate (NAR) is defined as the portion of pathologically normal appendices removed surgically in patients suspected of having acute appendicitis. The lifetime risk of acute appendicitis is 8.6% for males and 6.7% for females; contrarily, the lifetime risk of appendicectomy is 12% for males and 23.1% for females. This study aims primarily to evaluate the true NAR in females of childbearing age to offer insight into potential strategies to reduce the number of unnecessary operative procedures carried out, along with their associated morbidity and mortality. Methods All emergency appendicectomies over a one-year period were retrospectively identified and collected from a single tertiary care centre. Preoperative clinical, laboratory and postoperative histopathological data were collected. The negative appendicectomy rate in subgroups divided by biomarkers and radiological imaging findings were analysed. The diagnostic value of these modalities in the context of acute appendicitis was found by calculating the sensitivity, specificity, positive predictive values, and negative predictive values. Results A total of 417 patients were included (median age 26; M:F, 0.7:1.0). The overall negative appendicectomy rate was 35.0% (146/417). Two-hundred sixty-one patients underwent an appendicectomy in the child-bearing age group. The NAR was significantly higher in those females with raised WBC and C-reactive protein (CRP) compared to their male counterparts (p-value -<0.001). Conclusion Women of childbearing age have a higher NAR of 43% when compared to the general population of 35%. Preoperative tests, including ultrasound scans, computed tomography and inflammatory markers in blood tests, help direct those who would benefit from surgery to the operating theatre, however, no test alone is suitably sensitive or specific. To reduce the NAR, management options include a return to observation and serial examination, increased use of low-dose CT or a commitment to improving the performance of ultrasonography.
Introduction Healthcare systems across the world have struggled as a result of the Covid-19 pandemic. Most specialties have redeployed their staff and resources to deal with the pandemic whilst ceasing their planned elective activity. However acute specialties such as Trauma and Orthopaedics still have a significant emergency caseload that must be safely managed, even in a pandemic. The aim of this study was to investigate the change in Orthopaedic Trauma caseload in a Trauma Unit and a Major Trauma Centre during a pandemic compared to pre-pandemic levels and the associated staffing requirements. Methods The data presented was collected from a Trauma Unit and a Major Trauma Centre in the United Kingdom. We compared the number of accident and emergency referrals, fracture clinic appointments, inpatient admissions and operations during the six weeks of the first lockdown from 23rd March to 3rd May 2020, to the same time period in 2019. Results The results showed that the orthopaedic trauma caseload was approximately half that of pre-pandemic levels, reducing by an average of 54.2%. Conclusion A significant orthopaedic trauma caseload still remains to be safely managed during a pandemic and appropriate resources must be allocated. Staff allocation must take into account sick cover and staff wellbeing. A proportion of staff may need to be ring fenced from redeployment to facilitate this.
Introduction Complications following mandibular fractures occur in 9–23% of patients. Identifying those at risk is key to prevention. Previous studies highlighted smoking, age and time from injury to presentation as risk factors but rarely recorded other possible confounders. In this paper, we use a collaborative snapshot audit to document novel risk factors and confirm established risks for complications following the treatment of mandibular fractures. Methods The audit was carried out by 122 OMFS trainees across the UK and Ireland (49 centres) over 6 months, coordinated by the Maxillofacial Surgery Trainees Research Collaborative. Variables recorded included basic demography, medical and social history, injury mechanism and type, management and 30-day outcome. Results Nine hundred and forty-seven (947) patients with fractured mandibles were recorded. Surgical management was carried out in 76.3%. Complications at 30 days occurred 65 (9%) of those who were managed surgically. Risk factors for complications included male sex, increasing age, any medical history, increasing number of cigarettes smoked per week, increasing alcohol use per week, worse oral hygiene and increased time from injury to presentation. Discussion We have used a large prospective snapshot audit to confirm established risk factors and identify novel risk factors. We demonstrate that time from injury to presentation is confounded by other indicators of poor health behaviour. These results are important in designing trial protocols for management of mandibular fractures and in targeting health interventions to patients at highest risk of complications.
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178 members
Kar Hao Teoh
  • Department of Trauma and Orthopaedic Surgery
Vardhini Vijay
  • Department of Surgery
Jaspal S Virdi
  • Department of Urology
Arif Gul
  • Orthopaedics
Hossam El Gendi
  • Department of Cardiology
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Harlow, United Kingdom