Is pelvic ultrasound useful in the clinical assessment and management of women with right iliac fossa pain? A single-centre retrospective study.

INTRODUCTION: Acute right iliac fossa (RIF) pain is a common presenting symptom in surgical patients, with a wide range of differentials, particularly in premenopausal females. This study explores ultrasound usage in the management of women aged 16-55 years presenting with RIF pain. METHODS: A total of 1,082 patients who presented to a tertiary hospital over 12 months were included. Data were collected from patients' electronic records, including initial clinical impression, imaging, management, operative findings, histology and subsequent hospital attendances within 6 weeks and within 6 months. RESULTS: Following clinical assessment, 607 (56%) of patients underwent an ultrasound. Of these, 280 (25.9%) patients received no radiological imaging on initial presentation, and 252 (42%) had pathology identified on ultrasound. The most common finding was an ovarian cyst, closely followed by unexplained free pelvic fluid. Of the 607 patients scanned, 29 (4.8%) had an ultrasound diagnosis of appendicitis; 254 of 1,082 (23.5%) patients underwent operative management. Of the 254 patients who had surgery, 179 (70.5%) had preoperative imaging. Of the 29 (11.4%) cases where the intraoperative finding was gynaecological, 15 (51.7%) cases had not had any preoperative imaging. The negative appendicectomy rate was 21.3% (45/211). Of the 45 patients who had a histologically normal appendix, 22 (48.9%) had not had any previous imaging. Ultrasound had a specificity of 78% for diagnosing appendicitis. CONCLUSIONS: In patients who underwent operative management, a negative finding or finding not requiring surgical management was associated with no preoperative imaging. This supports the use of ultrasound scans as an adjunct in a multimodal approach to the assessment of women presenting with RIF pain.

Validation of metastasis-free survival as a surrogate endpoint for overall survival in localized prostate cancer in the era of docetaxel for castration-resistant prostate cancer.

BACKGROUND: Prior work from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium (ICECaP-1) demonstrated that metastasis-free survival (MFS) is a valid surrogate for overall survival (OS) in localized prostate cancer (PCa). This was based on data from patients treated predominantly before 2004, prior to docetaxel being available for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate surrogacy in a more contemporary era (ICECaP-2) with greater availability of docetaxel and other systemic therapies for mCRPC. PATIENTS AND METHODS: Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for localized PCa, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS was defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R2 ≥ 0.7 defined a priori as clinically relevant. RESULTS: A total of 15 164 IPD from 14 trials were included in ICECaP-2, with 70% of patients treated after 2004. The median follow-up was 8.3 years and the median postmetastasis survival was 3.1 years in ICECaP-2, compared with 1.9 years in ICECaP-1. For surrogacy condition 1, Kendall's tau was 0.92 for MFS with OS at the patient level, and R2 from weighted linear regression (WLR) of 8-year OS on 5-year MFS was 0.73 (95% confidence interval 0.53-0.82) at the trial level. For condition 2, R2 was 0.83 (95% confidence interval 0.64-0.89) from WLR of log[hazard ratio (HR)]-OS on log(HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. CONCLUSIONS: MFS remained a valid surrogate for OS in a more contemporary era, where patients had greater access to docetaxel and other systemic therapies for mCRPC. This supports the use of MFS as the primary outcome measure for ongoing adjuvant trials in localized PCa.

Issue 2 - "Update on adverse respiratory effects of indoor air pollution". Part 2): Indoor air pollution and respiratory diseases: Perspectives from Italy and some other GARD countries.

OBJECTIVE: to synthesize the Italian epidemiological contribution to knowledge on indoor pollution respiratory impact, and to analyze the perspective of some GARD countries on the health effects of indoor air pollution. RESULTS: Italian epidemiological analytical studies confirmed a strong relationship between indoor air pollution and health in general population. Environmental tobacco smoke, biomass (wood/coal) fuel for cooking/heating and indoor allergens (house dust mites, cat and dog dander, mold/damp) are the most relevant indoor pollution sources and are related to respiratory and allergic symptoms/diseases in Italy and in other GARD countries such as Mexico, Brazil, Vietnam, India, Nepal and Kyrgyzstan. Community-based global health collaborations are working to improve prevention, diagnosis and care of respiratory diseases around the world, specially in low- and middle-income countries, through research and education. CONCLUSIONS: in the last thirty years, the scientific evidence produced on respiratory health effects of indoor air pollution has been extensive, but the necessity to empower the synergies between scientific community and local administrations remains a challenge to address in order to implement effective interventions. Based on abundant evidence of indoor pollution health effect, WHO, scientific societies, patient organizations and other members of the health community should work together to pursue the GARD vision of "a world where all people breathe freely" and encourage policy makers to increase their engagement in advocacy for clean air.

The therapeutic and commercial landscape of stem cell vesicles in regenerative dermatology.

Extracellular vesicles (EVs) are lipid enveloped nanoparticles that are naturally produced by cells and function in the intercellular transfer of biological material such as proteins, RNAs and metabolites. They have been shown to act in an autocrine and paracrine manner to alter the functions of local and distant recipient cells, with a growing body of evidence highlighting their wide-ranging functions in regenerative processes such as stem cell maintenance, tissue repair and immune modulation. EVs offer several potential advantages over stem cell therapies such as improved safety profiles, scalability, and enhanced storage and quality control of the final product. In fact, many of the pro-regenerative outcomes of stem cell therapies have been attributed to the release of mesenchymal stem cell-derived EVs (MSC-EVs) and their potent effects on extracellular matrix turnover, local cell recruitment, proliferation and angiogenesis is now well described. These positive outcomes have led to clinical trials assessing the safety of MSC-EVs for applications in wound healing and the treatment of cutaneous ulcers, as well as the emergence of multiple commercial MSC-EV sources marketed for topical application in cosmetic medicine. However, regenerative EV therapeutics remain in their infancy and pertinent questions regarding product standardisation, potency and the regulatory landscape surrounding the development of these promising nano-therapeutics must be addressed to ensure safe and effective clinical adoption. In this article we provide an overview of the emerging landscape of MSC-EVs in regenerative dermatology and cosmetic science, highlighting the underlying biological mechanisms pertinent to their application and providing a perspective on current safety considerations, regulation and future directions in the field.

Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.

Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study.

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions. INTRODUCTION: The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723). METHODS: Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model. RESULTS: Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts. CONCLUSIONS: Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression.

BACKGROUND: Protection of islets without systemic immunosuppression has been a long-sought goal in the islet transplant field. We conducted a pilot biocompatibility/safety study in healthy dogs followed by a dose-finding efficacy study in diabetic dogs using polyethylene glycol diacrylate (PEGDA) microencapsulated allogeneic canine islets. METHODS: Prior to the transplants, characterization of the canine islets included the calculations determining the average cell number/islet equivalent. Following measurements of purity, insulin secretion, and insulin, DNA and ATP content, the islets were encapsulated and transplanted interperitoneally into dogs via a catheter, which predominantly attached to the omentum. In the healthy dogs, half of the microspheres injected contained canine islets, the other half of the omentum received empty PEGDA microspheres. RESULTS: In the biocompatibility study, healthy dogs received increasing doses of cells up to 1.7 M cells/kg body weight, yet no hypoglycemic events were recorded and the dogs presented with no adverse events. At necropsy the microspheres were identified and described as clear with attachment to the omentum. Several of the blood chemistry values that were abnormal prior to the transplants normalized after the transplant. The same observation was made for the diabetic dogs that received higher doses of canine islets. In all diabetic dogs, the insulin required to attempt to control blood glucose was cut by 50-100% after the transplant, down to no required insulin for the course of the 60-day study. The dogs had no adverse events and behavioral monitoring suggested normal activity after recovery from the transplant. CONCLUSIONS AND IMPLICATIONS: The study provides evidence that PEGDA microencapsulated canine islets reversed the signs of diabetes without immunosuppression and led to states of insulin-independence or significantly lowered insulin requirements in the recipients.

Transcriptomic and cellular decoding of functional brain connectivity changes reveal regional brain vulnerability to pro- and anti-inflammatory therapies.

BACKGROUND: Systemic inflammation induces acute changes in mood, motivation and cognition that closely resemble those observed in depressed individuals. However, the mechanistic pathways linking peripheral inflammation to depression-like psychopathology via intermediate effects on brain function remain incompletely understood. METHODS: We combined data from 30 patients initiating interferon-α treatment for Hepatitis-C and 20 anti-tumour necrosis factor (TNF) therapy for inflammatory arthritis and used resting-state functional magnetic resonance imaging to investigate acute effects of each treatment on regional global brain connectivity (GBC). We leveraged transcriptomic data from the Allen Human Brain Atlas to uncover potential biological and cellular pathways underpinning regional vulnerability to GBC changes induced by each treatment. RESULTS: Interferon-α and anti-TNF therapies both produced differential small-to-medium sized decreases in regional GBC. However, these were observed within distinct brain regions and the regional patterns of GBC changes induced by each treatment did not correlate suggesting independent underlying processes. Further, the spatial distribution of these differential GBC decreases could be captured by multivariate patterns of constitutive regional expression of genes respectively related to: i) neuroinflammation and glial cells; and ii) glutamatergic neurotransmission and neurons. The extent to which each participant expressed patterns of GBC changes aligning with these patterns of transcriptomic vulnerability also correlated with both acute treatment-induced changes in interleukin-6 (IL-6) and, for Interferon-α, longer-term treatment-associated changes in depressive symptoms. CONCLUSIONS: Together, we present two transcriptomic models separately linking regional vulnerability to the acute effects of interferon-α and anti-TNF treatments on brain function to glial neuroinflammation and glutamatergic neurotransmission. These findings generate hypotheses about two potential brain mechanisms through which bidirectional changes in peripheral inflammation may contribute to the development/resolution of psychopathology.

Large-scale serum analysis identifies unique systemic biomarkers in psoriasis and hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in HS with psoriasis is lacking. OBJECTIVES: To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity. METHODS: In this cross-sectional study, 1536 serum proteins were assessed using the Olink Explore (Proximity Extension Assay) high-throughput panel in patients with moderate-to-severe HS (n = 11), patients with psoriasis (n = 10) and age- and body mass index-matched healthy controls (n = 10). RESULTS: HS displayed an overall greater dysregulation of circulating proteins, with 434 differentially expressed proteins (absolute fold change ≥ 1·2; P ≤ 0·05) in patients with HS vs. controls, 138 in patients with psoriasis vs. controls and 503 between patients with HS and patients with psoriasis. Interleukin (IL)-17A levels and T helper (Th)1/Th17 pathway enrichment were comparable between diseases, while HS presented greater tumour necrosis factor- and IL-1ß-related signalling. The Th17-associated markers peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) were able to differentiate psoriasis from HS accurately. Both diseases presented increases of atherosclerosis-related proteins. Robust correlations between clinical severity scores and immune and atherosclerosis-related proteins were observed across both diseases. CONCLUSIONS: HS and psoriasis share significant Th1/Th17 enrichment and upregulation of atherosclerosis-related proteins. Despite the greater body surface area involved in psoriasis, HS presents a greater serum inflammatory burden.

Epistaxis in people with hereditary haemorrhagic telangiectasia: surgical management and psychological impact.

From the emergency management of acute epistaxis to the surgical procedures for chronic epistaxis, this article covers the options available to control the archetypal symptom of hereditary haemorrhagic telangiectasia while exploring the psychological effect such a disease has on the patient.

Digital mammographic interpretation by UK radiographer mammographers: A JAFROC analysis of observer performance.

INTRODUCTION: Radiologists utilise mammography test sets to bench mark their performance against recognised standards. Using a validated test set, this study compares the performance of radiographer readers against previous test results for radiologists. METHODS: Under similar test conditions radiographer readers were given an established test set of 60 mammograms and tasked to identify breast cancer, they were measured against their ability to identify, locate and give a confidence level for cancer being present on a standard set of mammographic images. The results were then compared to previously published results for radiologists for similar or the same test sets. RESULTS: The 10 radiographer readers demonstrated similar results to radiologists and for lesion sensitivity were the highest scoring group. The study group score a sensitivity of 83; a specificity of 69.3 and lesion sensitivity of 74.8 with ROC and JAFROC scores of 0.86 and 0.74 respectively. CONCLUSION: Under test conditions radiographers are able to identify and accurately locate breast cancer in a range of complex mammographic backgrounds. IMPLICATIONS FOR PRACTICE: The study was performed under experimental conditions with results comparable to breast radiologists under similar conditions, translation of these findings into clinical practice will help address access and capacity issues in the timely identification and diagnosis of breast cancer.

Use of fertility preservation services in male reproductive-aged cancer patients.

While fertility preservation is a major concern among reproductive age cancer patients, little is known about access and use of fertility preserving services. We examined use of fertility preserving services among men with common solid tumors. A total of 3648 men age 18-40 including 2610 (71.6%) with testicular cancer, 939 (25.7%) with colorectal and 99 (2.7%) with prostate cancer were identified. Fertility preservation services were utilized in 9.3% of men overall including 4.1% who underwent fertility evaluation only and 7.8% who had a fertility preservation procedure. The rate of fertility preservation services rose from 6.6% (95%CI, 3.2-10.0) in 2008 to 12.4% (95%CI, 7.3-17.5) in 2017 (P = 0.04). Use of fertility preservation service was more common in patients with testicular (11.6%, aRR = 3.31; 95% CI 2.22-4.92) and prostate cancer (6.1%, aRR = 3.14; 95% CI 1.28-7.70) compared to those with colon cancer (3.4%). Younger men were more likely to utilize fertility preservation services. 11.5% of men age ≤ 35 years vs. 5.2% of men 36-40 used these services (P < 0.0001). Fertility preservation services were used in 10.8% of those who received chemotherapy (aRR = 1.81; 95% CI, 1.45-2.27) and in 8.1% of those who received radiation (aRR = 1.30 95% CI, 0.98-1.73). Medicaid patients were less likely to receive fertility preservation services than those with commercial insurance (0.7% vs. 10.1%; aRR = 11.58, 95%CI 2.10-63.69). These data indicate that while use of fertility preserving services is increasing, overall use of services is low among reproductive age males with cancer.

Botulinum neurotoxin injections in essential infantile esotropia-a comparative study with surgery in large-angle deviations.

PURPOSE: To compare botulinum neurotoxin (BNT) injections to surgery as first-line therapy in large-angle essential infantile esotropia (IE). PATIENTS AND METHODS: Children between the ages 6 months and 6 years with IE of ≥40 prism dioptres (PD) were randomised to either a maximum of three BNT injections or surgical intervention of bimedial rectus muscle recession for angles ≤60 PD and augmented with BNT injection in angles >60 PD. Time taken for each procedure was documented. Orthophoria or misalignment of ≤10 PD was regarded as a complete response (CR). Follow-up visits were done at 3, 6, 12 and 24 weeks. RESULTS: Mean (SD) age and baseline angle of esotropia were 26.9 (14.5) months and 61.9 PD (12.8), respectively, for the overall cohort. The proportion of children who achieved CR was significantly higher in the surgery arm compared to the BNT injection arm (OR = 4.01, 95% CI 1.74-9.22) but the time taken was six times longer (p < 0.0001). In the BNT arm, 55.2% of children aged ≤24 months and 16% of children >24 months achieved CR. In children with esotropia ≤60 PD, CR was achieved in 50% while those with esotropia >60 PD CR was achieved in 25%. CONCLUSION: Surgery remains the gold standard for treatment of esotropia but BNT injection is a safe and effective alternative in children ≤24 m and with smaller angles of esotropia ≤60 PD in resource-limited centres.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Standard versus hypofractionated intensity-modulated radiotherapy for prostate cancer: assessing the impact on dose modulation and normal tissue effects when using patient-specific cancer biology.

Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 15.3% (p-value: <0.01) and 23.8% (p-value: 0.02) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 43.3% (p-value: < 0.01) and 41.8% (p-value: 0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.

Upskilling the surgical workforce for vascular access provision during the COVID-19 pandemic - The Salisbury experience.

A vascular access device is defined as a catheter inserted into veins allowing fluids and medicines to be delivered intravenously1. The need for such devices in acutely unwell patients has remained steady throughout the COVID-19 pandemic. We describe here our experience of up-skilling the resident plastic surgery and maxillofacial surgical registrars to provide a vascular access service to reduce the workload on our intensive care colleagues. We hope that our practice and an 'all hands on deck' approach to the utilisation of baseline skills within the existing workforce will inform other departments to help ease the burden on critical care departments as we progress through the next stages of the COVID-19 pandemic.

A multi-centre analysis of a decade of endoscopic pharyngeal pouch surgery in Cheshire and Merseyside.

BACKGROUND: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks. METHODS: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites. RESULTS: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres. CONCLUSION: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Voxel-level biological optimisation of prostate IMRT using patient-specific tumour location and clonogen density derived from mpMRI.

AIMS: This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches. METHODS: IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control. RESULTS: The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning. CONCLUSIONS: It was concluded that varying the dose distribution within the prostate to take account for each patient's clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.