Recent Submissions

  • Incidental finding of an undifferentiated sarcoma during lower limb Doppler ultrasound: a case report

    Eteng, Rajuno Ernest (2024-05)
    Introduction: Undifferentiated sarcoma is considered a rare and aggressive type of soft tissue sarcoma with the lower extremity reported as the common site for soft tissue sarcomas. Case presentation: We present a rare incidental finding of undifferentiated sarcoma during lower limb Doppler ultrasound with a presenting symptom of right thrombotic-like calf pain in a 49-year-old female. Discussion: On ultrasound, the presented undifferentiated sarcoma appeared as a large heterogeneous, oval-shaped, soft tissue mass deeply seated in the right calf with involvement of the soleus muscle. The features on ultrasound mimicked those of a hematoma; however, the possibility of the lesion being a haematoma was promptly ruled out with the demonstration of internal vascularity on colour Doppler application. The case was then referred to a sarcoma triage multidisciplinary team for a review. Magnetic resonance imaging, computed tomography and biopsy were parts of the diagnostic workup for this case, histology confirmed the soft tissue lesion to be an undifferentiated sarcoma. Emergency above knee amputation of the right leg was performed as part of the patient's treatment. Conclusion: This case report presents a rare incidental finding of undifferentiated sarcoma encountered during lower limb Doppler ultrasound causing thrombotic-like calf pain. Sonographers are encouraged to pay necessary attention and carefully examine any adjacent and incidental soft tissue lesion during lower limb Doppler ultrasound using compression, two-dimensional imaging and colour imaging, especially those that appear with characteristic features of malignancy; urgent referral should be made of such cases to a tertiary soft tissue sarcoma centre for further evaluation and management.
  • Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a multicentre, double-blind, randomised, placebo-controlled trial

    Hubbard, Marie (2024-04-25)
    Background: Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants. Methods: AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed. Findings: Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators. Interpretation: Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice. Funding: UK National Institute for Health and Care Research.
  • Leveraging the pleural space for anticancer therapies in pleural mesothelioma

    Darlison, Liz; Fennell, Dean (2024-05-10)
    Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies. Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.
  • Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial

    Fennell, Dean; Nelson, Louise (2024-05-10)
    Background: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. Methods: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. Findings: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. Interpretation: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. Funding: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895). Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
  • Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets

    Baruah, Paramita (2024-06)
    Background: Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown. Objectives: The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq). Methods: scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules. Results: scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume. Conclusions: Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.
  • A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes

    Graham-Brown, M P M; Hull, Katherine; Medcalf, James; Adenwalla, Sherna (2024-03)
    Background: Acute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales. Methods: Twenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established. Results: 989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality. Conclusions: Outcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.
  • Tertiary centre study highlights low inpatient deintensification and risks associated with adverse outcomes in frail people with diabetes

    Aftab, Faseeha; Fazil, Mohamed; Gallagher, Alison; Higgins, Kath; Lwin, Huin; Melson, Eka; Thomas, Anu; Thottungal, Kevin; Tun, HayMar (2024-03)
    Introduction: The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes. Methods: A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected. Results: Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication). Conclusion: The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.
  • Making research everybody's business-innovation to introduce foundation doctors to research

    Brunskill, Nigel; Choudhary, Pratik; Davies, Melanie; Screder, Sally (2024-03-05)
    In order to train a future workforce able to meet the needs of its patients it is vital to ensure that opportunities to engage in research are inbuilt to training programmes. This strategy meets national recommendations recently published by NIHR, RCP and GMC. A nationally funded expansion of 'standard' Foundation programmes offers a unique opportunity to develop innovative new posts which include exposure to clinical research. In NHSE Midlands a pilot Foundation Year two (F2) post in Diabetes Research was implemented in August 2022, embedded into a standard Foundation programme. Subjective evaluation of the post, by F2 doctors and trainers, has been very positive and a further two posts in Research and Innovation commence August 2023 and 2024. These unique and geographically co-located programmes also aim to support the widening participation in medicine agenda. This model could be adapted within any Foundation School.
  • A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures

    Singh, Harvinder (2024-04-22)
    Aims: Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods: The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England - Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024.
  • Comparison of interventions for lateral elbow tendinopathy: A systematic review and network meta-analysis for patient-rated tennis elbow evaluation pain outcome

    Dhingra, Mohit; Lowdon, Hamish; Singh, Harvinder Pal (2024-04-27)
    Purpose: There is controversy regarding the optimal treatment for lateral elbow tendinopathy (LET), and not all available treatment options have been compared directly with placebo/control. A network meta-analysis was conducted to compare the effectiveness of different LET treatments directly and indirectly against control/placebo based on a validated outcome, the Patient-Rated Tennis Elbow Evaluation (PRTEE) pain score. Methods: Randomized, controlled trials comparing different treatment methods for LET were included, provided they reported outcome data using the PRTEE pain score. A network meta-analysis with random effect was used to combine direct and indirect evidence between treatments compared with placebo in the short term (up to six weeks) and midterm (more than six weeks and up to six months) after intervention. Results: Thirteen studies with 12 comparators including control/placebo were eligible. The results indicated no significant improvement in PRTEE pain score in the short term across all treatments compared with control/placebo. In the midterm, physiotherapy/exercise showed benefit against placebo (mean difference: -4.32, 95% confidence interval: -7.58 and -1.07). Although steroid injections, dry needling, and autologous blood also exhibited potential treatment effects, it is crucial for the clinician to consider certain pitfalls when considering these treatments. The limited number of small studies and paucity of data call for caution in interpreting the results and need for further evidence. Conclusions: Patients should be informed that there is currently no strong evidence that any treatment produces more rapid improvement in pain symptoms when compared with control/placebo in the short and medium terms. Type of study/level of evidence: Therapeutic I.
  • A practical approach to screening for Carbapenemase-Producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals

    Jenkins, David (2024-04-26)
    Introduction: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. Methods: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. Key findings: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. Conclusion: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.
  • Serial postoperative circulating tumor DNA assessment has strong prognostic value during long-term follow-up in patients with breast cancer

    Ahmed, Samreen; Richards, Cathy (2024-04)
    Purpose: Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer. Methods: A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data. Results: Personalized Signatera assays detected ctDNA ahead of clinical or radiologic relapse in 30 of the 34 patients who relapsed (patient-level sensitivity of 88.2%). Relapse was predicted with a lead interval of up to 38 months (median, 10.5 months; range, 0-38 months), and ctDNA positivity was associated with shorter relapse-free survival (P < .0001) and overall survival (P < .0001). All relapsing triple-negative patients (n = 7/23) had a ctDNA-positive test within a median of 8 months (range, 0-19 months), while the 16 nonrelapsed patients with triple-negative breast cancer remained ctDNA-negative during a median follow-up of 58 months (range, 8-99 months). The four patients who had negative tests before relapse all had hormone receptor-positive (HR+) disease and conversely, five of the 122 nonrelapsed patients (all HR+) had an occasional positive test. Conclusion: Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. Our study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result.
  • Bronchoscopy-guided antimicrobial therapy for cystic fibrosis

    Jain, Kamini (2024-05-03)
    Background: Early diagnosis and treatment of lower respiratory tract infections is the mainstay of management of lung disease in cystic fibrosis (CF). When sputum samples are unavailable, diagnosis relies mainly on cultures from oropharyngeal specimens; however, there are concerns about whether this approach is sensitive enough to identify lower respiratory organisms. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL) are invasive but allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may increase the accuracy of diagnosis of lower respiratory tract infections and improve the selection of antimicrobials, which may lead to clinical benefits. This is an update of a previous review that was first published in 2013 and was updated in 2016 and in 2018. Objectives: To evaluate the use of bronchoscopy-guided (also known as bronchoscopy-directed) antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. Search methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. The date of the most recent searches was 1 November 2023. Selection criteria: We included randomised controlled studies involving people of any age with CF that compared the outcomes of antimicrobial therapies guided by the results of bronchoscopy (and related procedures) versus those guided by any other type of sampling (e.g. cultures from sputum, throat swab and cough swab). Data collection and analysis: Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information when required. We assessed the certainty of the evidence using the GRADE criteria. Main results: We included two studies in this updated review. One study enrolled 170 infants under six months of age who had been diagnosed with CF through newborn screening. Participants were followed until they were five years old, and data were available for 157 children. The study compared outcomes for pulmonary exacerbations following treatment directed by BAL versus standard treatment based on clinical features and oropharyngeal cultures. The second study enrolled 30 children with CF aged between five and 18 years and randomised participants to receive treatment based on microbiological results of BAL triggered by an increase in lung clearance index (LCI) of at least one unit above baseline or to receive standard treatment based on microbiological results of oropharyngeal samples collected when participants were symptomatic. We judged both studies to have a low risk of bias across most domains, although the risk of bias for allocation concealment and selective reporting was unclear in the smaller study. In the larger study, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was low because Pseudomonas aeruginosa isolation in BAL samples at five years of age in both groups were much lower than the expected rate that was used for the power calculation. We graded the certainty of evidence for the key outcomes as low, other than for high-resolution computed tomography scoring and cost-of-care analysis, which we graded as moderate certainty. Both studies reported similar outcomes, but meta-analysis was not possible due to different ways of measuring the outcomes and different indications for the use of BAL. Whether antimicrobial therapy is directed by the use of BAL or standard care may make little or no difference in lung function z scores after two years (n = 29) as measured by the change from baseline in LCI and forced expiratory volume in one second (FEV1) (low-certainty evidence). At five years, the larger study found little or no difference between groups in absolute FEV1 z score or forced vital capacity (FVC) (low-certainty evidence). BAL-directed therapy probably makes little or no difference to any measure of chest scores assessed by computed tomography (CT) scan at either two or five years (different measures used in the two studies; moderate-certainty evidence). BAL-directed therapy may make little or no difference in nutritional parameters or in the number of positive isolates of P aeruginosa per participant per year, but may lead to more hospitalisations per year (1 study, 157 participants; low-certainty evidence). There is probably no difference in average cost of care per participant (either for hospitalisations or total costs) at five years between BAL-directed therapy and standard care (1 study, 157 participants; moderate-certainty evidence). We found no difference in health-related quality of life between BAL-directed therapy and standard care at either two or five years, and the larger study found no difference in the number of isolates of Pseudomonas aeruginosa per child per year. The eradication rate following one or two courses of eradication treatment and the number of pulmonary exacerbations were comparable in the two groups. Mild adverse events, when reported, were generally well tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of BAL in 4.8% of procedures. Authors' conclusions: This review, limited to two well-designed randomised controlled studies, shows no evidence to support the routine use of BAL for the diagnosis and management of pulmonary infection in preschool children with CF compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence is available for adults.
  • From bench to bedside- is there a role of IL-17 drugs in rheumatoid arthritis?

    Moorthy, Arumugam (2024-05-02)
    Introduction: IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. Areas covered: This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. Expert opinion: The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.
  • Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes

    Zaccardi, Francesco (2024-06)
    Aim: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. Materials and methods: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. Results: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. Conclusions: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.
  • A systematic review and meta-analysis of 29 studies predicting diagnostic accuracy of CT, MRI, PET, and USG in detecting extracapsular spread in head and neck cancers

    Ameerally, Phil; Conboy, Peter; Mair, Manish; Oladejo, Olaleye; Salha, Rami; Vaidhyanath, Ram (2024-04-10)
    Background: Extracapsular spread (ECS) is the extension of cancer cells beyond the lymph node capsule and is a significant prognostic factor in head and neck cancers. This meta-analysis compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. Methodology: The authors conducted a systematic review and meta-analysis of studies that compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. They included studies that were published between 1990 and December 2023 and that used histopathology as the reference standard for ECS. Results: The pooled sensitivity and specificity of CT scan were 0.63 (95% CI = 0.53-0.73) and 0.85 (95% CI = 0.74-0.91), respectively. The pooled sensitivity and specificity of MRI were 0.83 (95% CI = 0.71-0.90) and 0.85 (95% CI = 0.73-0.92), respectively. The pooled sensitivity and specificity of PET were 0.80 (95% CI = 0.74-0.85) and 0.93 (95% CI = 0.92-0.94), respectively. The pooled sensitivity and specificity of USG were 0.80 (95% CI = 0.68-0.88) and 0.84 (95% CI = 0.74-0.91), respectively. MRI had significantly higher sensitivity than CT scan (p-0.05). The specificity of CT and MRI was not significantly different (p-0.99). PET scan had the highest specificity among all imaging modalities. Conclusion: MRI is the most accurate imaging modality for detecting ECS in head and neck cancers. CT scan is a reasonable alternative, but PET scan may be considered when high specificity is required. USG may not add any further benefit in detecting ECS.
  • MRI reporting radiographers - has there been a progression or regression in numbers and scope of practice?

    Estall, Helen (2024-05-03)
    Introduction: The aim of this study was to determine whether there had been a progression or regression in the numbers and scope of practice of reporting radiographers in Magnetic Resonance Imaging (MRI) in the United Kingdom (UK), using data from a previous study conducted by the author in 2019/20 as a comparison. Methods: Data was gathered via a survey sent to multiple users and groups of MRI Radiographers in the UK. The survey consisted of a questionnaire, using both numerical and free text answers to enable the responders to elaborate on their scope of practice whilst also allowing numerical data to be easily analysed. The responses were analysed for patterns and comparison was made with the data from the previous survey. The questionnaire was based on three main themes of those in training, those trained and those in practice. Results: A total of 62 sites had radiographers in training (n =24) or trained (n = 125) in MRI reporting compared to 46 sites in the previous survey. The majority of responders were from England (n = 56/62) with only a few sites in Scotland (n = 4) and Wales (n = 2). There were 24 radiographers in training, a reduction compared to the previous survey and an increase in the number of radiographers trained (n = 80 to n = 125) and in practice (n = 57 to n = 84). Scope of practice had also increased with the addition of MRCPs, orbits and pituitary. Conclusion: This survey provides evidence that the number and scope of practice of MRI reporting radiographers within the UK has progressed when compared to a previous survey from 2019/20. The numbers however are still low and there remain significant geographical variations. The continued predominance of single handed practice is a concern and the reasons behind this and the slow expansion of skill mix reporting in this modality needs further investigation. Implications for practice: This study provides evidence of the number and scope of practice of the radiographer reporting of MRI examinations in the UK. It also demonstrates that there has been an increase in scope and number of radiographers reporting MRI scans, this will provide evidence and proof of concept for departments looking to initiate or increase this practice.
  • Perceptions of theatre team members to robotic assisted surgery and the aid of technology in colorectal surgery

    Kulkarni, Shreya (2024-05-04)
    The implementation of robotic assisted surgery (RAS) has brought in a change to the perception and roles of theatre staff, as well as the dynamics of the operative environment and team. This study aims to identify and describe current perceptions of theatre staff in the context of RAS. 12 semi-structured interviews were conducted in a tertiary level university hospital, where RAS is utilised in selected elective settings. Interviews were conducted by an experienced research nurse to staff of the colorectal department operating theatre (nursing, surgical and anaesthetics) with some experience in operating within open, laparoscopic and RAS surgical settings. Thematic analysis on all interviews was performed, with formation of preliminary themes. Respondents all discussed advantages of all modes of operating. All respondents appreciated the benefits of minimally invasive surgery, in the reduced physiological insult to patients. However, interviewees remarked on the current perceived limitations of RAS in terms of logistics. Some voiced apprehension and anxieties about the safety if an operation needs to be converted to open. An overarching theme with participants of all levels and backgrounds was the 'Teamwork' and the concept of the [robotic] team. The physical differences of RAS changes the traditional methods of communication, with the loss of face-to-face contact and the physical 'separation' of the surgeon from the rest of the operating team impacting theatre dynamics. It is vital to understand the staff cultures, concerns and perception to the use of this relatively new technology in colorectal surgery.

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