Ectopic pregnancy (EP) is a major high-risk outcome following a pregnancy of unknown location (PUL) classification. Biochemical markers are used to triage PUL as high vs low risk to guide appropriate follow-up. The M6 model is currently the best risk-prediction model. We aimed to update the M6 model and evaluate whether performance can be improved by including clinical factors. This prospective cohort study recruited consecutive PUL between January 2015 and January 2017 at eight units (Phase 1), with two centers continuing recruitment between January 2017 and March 2021 (Phase 2). Serum samples were collected routinely and sent for β-human chorionic gonadotropin (β-hCG) and progesterone measurement. Clinical factors recorded were maternal age, pain score, bleeding score and history of EP. Based on transvaginal ultrasonography and/or biochemical confirmation during follow-up, PUL were classified subsequently as failed PUL (FPUL), intrauterine pregnancy (IUP) or EP (including persistent PUL (PPUL)). The M6 models with (M6P ) and without (M6NP ) progesterone were refitted and extended with clinical factors. Model validation was performed using internal-external cross-validation (IECV) (Phase 1) and temporal external validation (EV) (Phase 2). Missing values were handled using multiple imputation. Overall, 5473 PUL were recruited over both phases. A total of 709 PUL were excluded because maternal age was < 16 years or initial β-hCG was ≤ 25 IU/L, leaving 4764 (87%) PUL for analysis (2894 in Phase 1 and 1870 in Phase 2). For the refitted M6P model, the area under the receiver-operating-characteristics curve (AUC) for EP/PPUL vs IUP/FPUL was 0.89 for IECV and 0.84-0.88 for EV, with respective sensitivities of 94% and 92-93%. For the refitted M6NP model, the AUCs were 0.85 for IECV and 0.82-0.86 for EV, with respective sensitivities of 92% and 93-94%. Calibration performance was good overall, but with heterogeneity between centers. Net Benefit confirmed clinical utility. The change in AUC when M6P was extended to include maternal age, bleeding score and history of EP was between -0.02 and 0.01, depending on center and phase. The corresponding change in AUC when M6NP was extended was between -0.01 and 0.03. At the 5% threshold to define high risk of EP/PPUL, extending M6P altered sensitivity by -0.02 to -0.01, specificity by0.03 to 0.04 and Net Benefit by -0.005 to 0.006. Extending M6NP altered sensitivity by -0.03 to -0.01, specificity by 0.05 to 0.07 and Net Benefit by -0.005 to 0.006. The updated M6 model offers accurate diagnostic performance, with excellent sensitivity for EP. Adding clinical factors to the model improved performance in some centers, especially when progesterone levels were not suitable or unavailable. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

BackgroundStandardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres.MethodsConsensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies.ResultsThree consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital.ConclusionsThis consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units.

Abstract Introduction Mucosal melanoma (MM) is a rare disease, accounting for approximately 1.4% of all melanomas and only 0.03% of all new cancer diagnoses [1]. Traditionally, it is associated with a poor prognosis with an overall 5-year survival rate of less than 25%[1]. Progress in treatment has been hindered by rarity and lack of evidence. Studies however of treatment of subcutaneous melanoma with immunotherapy have demonstrated a significant improvement in survival rates and have become a core part of oncological strategy. This paper will discuss revision of the evidence for the use of immunotherapy in the Head and Neck. Design A systematic review was conducted on 19/01/2019. Medline and Embase databases were searched. 509 articles were collated, of which 52 met the inclusion criteria. Results Results were shown as a comparison of yearly survival rates following different treatment modalities (immunotherapy vs non-immunotherapy) at 2 years, 3 years, and 5 years respectively. Conclusions Immunotherapy outcomes in small studies have shown good data for increasing survival rates at all yearly intervals in MM of the head and neck. Larger clinical trials should be done to accurately distinguish efficacy and survival outcomes of immunotherapy when compared to treatment modalities excluding immunotherapy. The ability to perform larger trials are, however, limited by the rarity of MM of the head and neck.

Dextran, a microbial metabolite of diverse molecular configurations, can be biosynthesized employing selected strains of characterized species of bacteria. Dextran molecules are secreted as an extracellular polysaccharide in the culture medium of the bacterial fermentation system. This microbially produced polymer of glucose possesses multi-faceted characteristics such as its solubility in different solvents and formation of dextran solutions of needed viscosity. Several preparations can be formulated for the desired thermal and rheological properties. Due to such multifunctional characteristics, dextran with different structural specifications is a desired polysaccharide for clinical, pharmaceutical, and food industry commercial applications. Dextran and its derivative products with various molecular weights, in a range of high and low, have established their uses in drug delivery and in analytical devices using columns packed with polysaccharide gel. Therefore, being a neutral raw material, the resourcefulness of dextran preparations of different molecular weights and linkages in their polymer configuration is important. For this purpose, several studies have been performed to produce this commercially important polysaccharide under optimized bacterial cultivation processes. This article aims to overview recently published research reports on some significant applications of dextran in the pharmaceutical and food industries. Studies conducted under optimized conditions in fermentation processes for the biosynthesis of dextran of diverse molecular configurations, which are responsible for its multifunctional properties, have been summarized. Concise information has been presented in three separate tables for each group of specific bacterial species employed to obtain this extracellular microbial polysaccharide.

Abstract Background The incidence of symptomatic cholelithiasis continues to rise. We are now observing an increasing number of cases within an elderly, frail, co-morbid patient population. Gram-negative bacteraemia (GNB) secondary to cholelithiasis in this high-risk patient cohort carries a significant morbidity and mortality rate. Reducing GNB rates has been identified as a national target by Public Health England. Our aim is to evaluate the burden of GNB due to cholelithiasis and the management received in a district general hospital in order to inform approaches to reducing the burden of GNB. Methods A cross-site audit was conducted across two ‘hot’ district general hospitals serving approximately 1 million people within the same NHS foundation trust. Patients with positive blood cultures for GNB secondary to cholelithiasis were identified. Data was collected regarding patient demographics, survival outcomes, whether definitive treatment for cholelithiasis was performed on the index admission and re-admission rates. Results A total of 176 GNB patients from a microbiology database were analysed of which 69 (39%) were identified to have gallstone disease on index admission. Median age of the cohort was 81 years old. Only 10 patients (14%) received a cholecystectomy. Previous gallstone-related admission was found in 23 patients, therefore 23/176 (13%) of GNBs were potentially preventable. Assessment of fitness found 11/176 (6%) were preventable as they were fit for surgery at index non-GNB biliary admission, 4 patients were on a waiting list. Overall, 25 patients were unfit for surgery of which 12 received a drain and 6 were readmitted. Conclusions This audit demonstrated a significant proportion of GNB is caused by gallstone disease however a minority of patients are receiving surgery during admission, relinquishing the opportunity to prevent readmission in surgically fit patients. With long waiting times for elective procedures, combatting the burden of GNB requires a shift towards the use of acute cholecystectomy lists. With an increasingly frail population optimal non-operative management is essential to reducing GNB burden, almost half of these patients received a drain which evidence suggests does not reduce recurrence. Greater use of cystic duct stents advised by NICE in this cohort may reduce GNB admissions.

The study was an analysis of patients managed by plastic surgery services at Heatherwood and Wexham Park hospitals during the calendar year 2022 for complications following cosmetic surgeries performed both internationally and within the United Kingdom. Patients were identified via local databases and encounters and management confirmed with retrospective studies of patient electronic medical records. 23 patients were managed during the year 2022 for complications post cosmetic surgery. 91% (n=21) of complications were related to breast cosmetic surgery and/or abdominoplasties. 78% (n=18) of patients presented within the first two months following their procedure. The most common complications identified were wound dehiscence 43% (n=10), post-operative infection 39% (n=9) and seromas 30% (n=7). The most common country selected for surgery by patients was Turkey with 48% (n=11) of managed patients. 52% (n=12) of cases were managed conservatively and 48% (n=11) of cases required invasive procedures including surgery. 87% (n=20) of patients were discharged with completed treatment. Cosmetic surgery and tourism are an in-demand phenomenon and appear here to stay. The stringent regulatory and legal processes in place in the UK may not be applicable abroad to the detriment of patient care. Greater effort is needed to increase public awareness to the risks involved in seeking international options and how to self-screen suitable clinics. Ongoing current national auditing may need to be expanded to understand the true impact on NHS units in dealing with the aftermath of these surgical expeditions.

We present the case of a 70-year-old woman presenting with nausea, diarrhoea and a generalised rash. Initial blood tests revealed obstructive deranged liver function tests and low haemoglobin. A haemolysis screen revealed raised reticulocytes, low haptoglobin and a positive direct antiglobulin test. 6 days into her admission, she developed lower limb weakness and loss of sensation. MRI spine showed no significant findings. Cerebrospinal fluid showed raised white blood cell count and raised protein. Nerve conduction studies were normal. The clinical picture was in keeping with transverse myelitis. Autoimmune and viral screens were negative except for a single result which provided the unifying diagnosis: Epstein-Barr virus (EBV). She responded to high dose intravenous corticosteroids and her rehabilitation is ongoing. EBV should be considered even in the older population.

BackgroundThe COVID-19 pandemic caused >750 million infections and just under 7 million deaths worldwide, along with shutdowns in social and economic activities. Respiratory particles produced during non-vocalised activities such as breathing, and vocal activities including singing and speaking serve as a major route for respiratory viral disease transmission.MethodsThis work reports concomitant measurements of the exhaled volume of carbon dioxide (VCO2) and minute ventilation (VE), along with respiratory aerosol emitted during breathing, exercising, speaking, and singing, across 33 healthy adult participants.ResultsVCO2 and VE appear to follow a similar trend to aerosol number concentration during the non-vocalised, exercise activities. Vigorous and very vigorous exercises generated 6 and 10 times more exhaled CO2 (L/min) than breathing at rest (p<0.001), ~5 and 8 times greater VE than breathing (p<0.001), respectively. And both vigorous and very vigorous exercise generated significantly more aerosol particles than breathing (p < 0.001). When considering non-vocalised activities (breathing at rest, vigorous exercise, and very vigorous exercise), a strong correlation (R2 = 0.71) between exhaled CO2 production (in mL/s) and mean aerosol mass emission rates is evident. During vocalisation the amount of exhaled CO2 when breathing at rest was similar to that exhaled while speaking (p=0.27) and singing at 70–80 dBA (p=0.23) and only modestly different to that emitted when singing at 90–100 dBA (p=0.02). Conversely, speaking and singing at 70–80 dBA, and singing at 90–100 dBA, generated significantly more aerosol particles than breathing (p<0.001). Consequently, a relatively poor correlation (R2 = 0.02) was observed between exhaled CO2 production in (mL/s) and mean aerosol mass emission during vocalization. P100 Figure 1Box and whisker plots showing time averaged aerosol particle number concentrations in #/cm3 (blue), minute ventilation in L/min (grey), and exhaled carbon dioxide in L/min (red) for the same series of activities (breathing at rest (n = 33), vigorous exercise (n = 25), very vigorous exercise (n = 25), speaking (n = 33), singing at 70–80 dBA (n = 8), and singing at 90–100 dBA (n = 8) across all relevant participants. BoxesConclusionThe correlation between the aerosol mass exhalation and VCO2 is only observed across activities that do not involve vocalisation, i.e. from breathing at rest through to vigorous exercise. Subsequently, using CO2 as a surrogate measure of respirable aerosol in, for example, an indoor space provides and underestimation of the amount of airborne respiratory pathogen exhaled by an infected individual when they are vocalising. Therefore, additional surrogate measures are needed for vocalising.