Co-design of an intervention to optimize mammographic screening participation in women with obesity and/or physical disabilities.

BACKGROUND: Mammographic breast screening/rescreening rates are suboptimal for women with obesity and/or physical disabilities. This study describes development of an intervention framework targeting obesity- and disability-related barriers to improve participation. METHODS: Mixed methods combined a systematic review with first-person perspectives to optimise screening engagement among women with obesity and/or physical disabilities. Phase 1 (systematic review) was conducted following the PRISMA framework. Phase 2 involved in-depth interviews with n = 8 women with lived experience of obesity and/or physical disabilities. An inductive coding approach was applied to the data which was then combined with Phase 1 results to develop the intervention framework. RESULTS: Six studies were included in the systematic review. Tailored education based on individual risk increased willingness to undergo mammographic screening. Recommendations to improve the screening experience included partnerships with consumers, targeted messaging, and enhanced professional development for breast screening staff. Participants also identified strategies to improve the uptake of screening and the experience itself. CONCLUSION: Development and evaluation of interventions informed by frameworks like the one developed in this study are needed to improve engagement in screening to promote regular participation among women with physical disabilities and/or obesity. IMPLICATIONS FOR PRACTICE: Successful implementation of practice interventions co-designed by women with obesity and/or physical disabilities are likely to improve their breast screening participation. Enhanced training of radiographers aimed at upskilling in empathetic communication around required manoeuvring and potentially longer screening times for clients with obesity and/or physical disabilities may encourage more positive client practitioner interactions. Client information aimed at women with obesity should include information on how to prepare for the appointment and explain there may be equipment limitations compromising imaging which may not be completed at an initial appointment.

Illness representations of people with later-onset functional seizures.

PURPOSE: Although functional seizures can start at any age, little is known about the individuals for whom onset occurs after the age of 40. It has been proposed that health-related traumatic events are more relevant causal factors for people with 'later-onset functional seizures' than for those whose functional seizures begin earlier in life, however, the illness representations of people with later-onset functional seizures have not yet been investigated. This study aimed to understand the experiences and illness representations of people with later-onset functional seizures. METHODS: This was a mixed-methods study. People with later-onset functional seizures were recruited via a neurologist's caseload and online membership-led organisations. Semi-structured interview transcripts were analysed using Template Analysis according to the Common-Sense Model (CSM). Self-report measures of demographic and clinical details were collected to characterise the sample and verify themes. RESULTS: Eight people with later-onset functional seizures participated in the study. Illness representations relating to all domains of the CSM as well as an additional theme of 'Triggers' were identified. Functional seizures were characterised as a mysterious brain disorder analogous to a computer malfunction and involving involuntary movements associated with alterations in consciousness. Perceptions of duration were indefinite, and triggers were unknown or at the extremes of autonomic arousal. Half of the sample identified health-related events/trauma as causal. Opinions were divided on 'cumulative life stress' as a causal factor. Most perceived themselves to have limited or no control but having 'control' over seizures was conceptualised as different to reducing their likelihood, frequency, or impact. Later-onset functional seizures were viewed as being more detrimental for caring and financial responsibilities but to have advantages for acceptance. CONCLUSIONS: This is the first study to assess the illness representations of people with later-onset functional seizures. Many themes were similar to those identified in samples including people with earlier-onset functional seizures. Health-related trauma or events were the most strongly endorsed perceived causal factor, but with the exception of 'consequences', all representations were characterised by uncertainty. Clinicians should hold in mind the interaction between life stage and the consequences of later-onset functional seizures.

Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacterium and Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along with enrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alterations that allow disease progression in esophageal cancer.

How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Has the HCV cascade of care changed among people who inject drugs in England since the introduction of direct-acting antivirals?

BACKGROUND: In England, over 80 % of those with hepatitis C virus (HCV) infection have injected drugs. We quantified the HCV cascade of care (CoC) among people who inject drugs (PWID) in England and determined whether this improved after direct-acting antivirals (DAAs) were introduced. METHODS: We analysed data from nine rounds of national annual cross-sectional surveys of PWID recruited from drug services (2011-2019; N = 12,320). Study rounds were grouped as: 'Pre-DAAs' (2011-2014), 'Prioritised DAAs' (2015-2016) and 'Unrestricted DAAs' (2017-2019). Participants were anonymously tested for HCV antibodies and RNA and completed a short survey. We assessed the proportion of PWID recently (current/previous year) tested for HCV. For participants ever HCV treatment eligible (past chronic infection with history of treatment or current chronic infection), we assessed the CoC as: HCV testing (ever), received a positive test result, seen a specialist nurse/doctor, and ever treated. We used logistic regression to determine if individuals progressed through the CoC differently depending on time-period, whether time-period was associated with recent testing (all participants) and lifetime HCV treatment (ever eligible participants), and predictors of HCV testing and treatment in the Unrestricted DAAs period. RESULTS: The proportion of ever HCV treatment eligible PWID reporting lifetime HCV treatment increased from 12.5 % in the Pre-DAAs period to 25.6 % in the Unrestricted DAAs period (aOR:2.40, 95 %CI:1.95-2.96). There were also increases in seeing a specialist nurse/doctor. The largest loss in the CoC was at treatment for all time periods. During the Unrestricted DAAs period, recent (past year) homelessness (vs never, aOR:0.66, 95 %CI:0.45-0.97), duration of injecting (≤3 years vs >3 years; aOR:0.26, 95 %CI:0.12-0.60), never (vs current, aOR:0.31, 95 %CI:0.13-0.75) or previously being prescribed OAT (vs current, aOR:0.67, 95 %CI:0.47-0.95), and never using a NSP (vs past year, aOR:0.27, 95 %CI:0.08-0.89) were negatively associated with lifetime HCV treatment. The proportion of PWID reporting recent HCV testing was higher during Unrestricted DAAs (56 %) compared to Pre-DAAs (48 %; aOR:1.28, 95 %CI:1.06-1.54). CONCLUSION: COC stages from seeing a specialist onwards improved after DAAs became widely available. Further improvements in HCV testing are needed to eliminate HCV in England.

Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS: We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.

Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.

Moderators of cognitive behavioural therapy treatment effects and predictors of outcome in the CODES randomised controlled trial for adults with dissociative seizures.

OBJECTIVE: We explored moderators of cognitive behavioural therapy (CBT) treatment effects and predictors of outcome at 12-month follow-up in the CODES Trial (N = 368) comparing CBT plus standardised medical care (SMC) vs SMC-alone for dissociative seizures (DS). METHODS: We undertook moderator analyses of baseline characteristics to determine who had benefited from being offered CBT 12 months post-randomisation. Outcomes included: monthly DS frequency, psychosocial functioning (Work and Social Adjustment Scale - WSAS), and health-related quality of life (Mental Component Summary (MCS) and Physical Component Summary (PCS) SF-12v2 scores). When moderating effects were absent, we tested whether baseline variables predicted change irrespective of treatment allocation. RESULTS: Moderator analyses revealed greater benefits (p < 0.05) of CBT on DS frequency for participants with more (≥22) symptoms (Modified PHQ-15) or ≥ 1 current (M.I.N.I.-confirmed) comorbid psychiatric diagnosis at baseline. The effect of CBT on PCS scores was moderated by gender; women did better than men in the CBT + SMC group. Predictors of improved outcome included: not receiving disability benefits, lower anxiety and/or depression scores (PCS, MCS, WSAS); shorter duration, younger age at DS onset, employment, fewer symptoms and higher educational qualification (PCS, WSAS); stronger belief in the diagnosis and in CBT as a "logical" treatment (MCS). Some variables that clinically might be expected to moderate/predict outcome (e.g., maladaptive personality traits, confidence in treatment) were not shown to be relevant. CONCLUSION: Patient complexity interacted with treatment. CBT was more likely to reduce DS frequency in those with greater comorbidity. Other patient characteristics predicted outcome regardless of the received intervention.

Gender diversity in therapeutic radiography: A mixed methods exploration of the gender influences impacting on male students' career choices.

INTRODUCTION: A significant gender imbalance exists in therapeutic radiography, with male radiographers contributing to less than one fifth of the UK registered workforce. This research aimed to explore male student recruitment experiences to identify gender-sensitive strategies to employ within future recruitment drives. METHODS: An exploratory mixed methods design commenced with therapeutic radiography student focus groups, analysed via descriptive thematic analysis. The focus group themes informed an online questionnaire survey targeting enrolled male therapeutic radiography students in the UK. Both phases explored students' experiences of their career choice and the impact, if any, their gender had on this selection. RESULTS: Three focus groups (n = 9) yielded four major themes: the invisible profession; career choices; gender influences; gender-sensitive approaches. Survey responses (n = 38) represented 9 UK institutions, a 25% estimated response rate. Over half (55%) had little or no awareness of the career at entry, with many discovering the profession 'by accident'. Many had never seen recruitment materials; 40% (n = 15) stated they were not designed to appeal to male applicants, with 18% (n = 7) suggesting they reflected more stereotypical female traits. CONCLUSION: Targeting gender imbalances is always controversial but doing nothing will maintain the status quo and perpetuate an unrepresentative workforce. Earlier awareness-raising of therapeutic radiography is essential, with promotional imagery suitable for different audiences and focusing equally on care and technology. Recruitment language should embrace 'leadership' attributes as well as 'caring' attributes. Supported by male role models, outreach events should emphasise the profession in terms of a sustainable, fulfilling and rewarding career. IMPLICATIONS FOR PRACTICE: The findings have provided detailed recommendations on which to focus a specific recruitment and marketing strategy to encourage male applicants to consider a career in therapeutic radiography.

Online psychological interventions to reduce symptoms of depression, anxiety, and general distress in those with chronic health conditions: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Over the past 15 years, there has been substantial growth in web-based psychological interventions. We summarize evidence regarding the efficacy of web-based self-directed psychological interventions on depressive, anxiety and distress symptoms in people living with a chronic health condition. METHOD: We searched Medline, PsycINFO, CINAHL, EMBASE databases and Cochrane Database from 1990 to 1 May 2019. English language papers of randomized controlled trials (usual care or waitlist control) of web-based psychological interventions with a primary or secondary aim to reduce anxiety, depression or distress in adults with a chronic health condition were eligible. Results were assessed using narrative synthases and random-effects meta-analyses. RESULTS: In total 70 eligible studies across 17 health conditions [most commonly: cancer (k = 20), chronic pain (k = 9), arthritis (k = 6) and multiple sclerosis (k = 5), diabetes (k = 4), fibromyalgia (k = 4)] were identified. Interventions were based on CBT principles in 46 (66%) studies and 42 (60%) included a facilitator. When combining all chronic health conditions, web-based interventions were more efficacious than control conditions in reducing symptoms of depression g = 0.30 (95% CI 0.22-0.39), anxiety g = 0.19 (95% CI 0.12-0.27), and distress g = 0.36 (95% CI 0.23-0.49). CONCLUSION: Evidence regarding effectiveness for specific chronic health conditions was inconsistent. While self-guided online psychological interventions may help to reduce symptoms of anxiety, depression and distress in people with chronic health conditions in general, it is unclear if these interventions are effective for specific health conditions. More high-quality evidence is needed before definite conclusions can be made.

Patients with resolution of low-lying placenta and placenta previa remain at increased risk of postpartum hemorrhage.

OBJECTIVE: To determine whether women who experience resolution of low placentation (low-lying placenta or placenta previa) are at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. METHODS: This was a retrospective cohort study of women who delivered at Mount Sinai Hospital between 2015 and 2019, and who were diagnosed with low-lying placenta or placenta previa on transvaginal ultrasound at the time of the second-trimester anatomical survey, with resolution of low placentation on subsequent ultrasound examination. Women undergoing second-trimester anatomical survey who had normal placentation on transvaginal ultrasound 3 days before or after the cases were randomly identified for comparison. The primary outcome was the rate of postpartum hemorrhage. Secondary outcomes included the need for a blood transfusion, use of additional uterotonic medication, the need for additional procedures to control bleeding, and maternal admission to the intensive care unit. Outcomes were assessed using a multivariable logistic regression model. RESULTS: A total of 1256 women were identified for analysis, of whom 628 had resolved low placentation and 628 had normal placentation. Women with resolved low placentation, compared to those with normal placentation throughout pregnancy, had significantly higher mean age (33.0 ± 5.4 years vs 31.9 ± 5.5 years; P < 0.01) and lower mean body mass index at delivery (27.9 ± 5.5 kg/m2 vs 30.2 ± 5.7 kg/m2 ; P < 0.01), and were more likely to have undergone in-vitro fertilization, be of non-Hispanic white race, have posterior placental location (all P < 0.01) and have private/commercial health insurance (P = 0.04). Patients with resolved low placentation vs normal placentation had greater odds of postpartum hemorrhage (adjusted odds ratio (aOR), 3.5 (95% CI, 2.0-6.0); P < 0.01), use of additional uterotonic medication (aOR, 2.2 (95% CI, 1.5-3.1); P < 0.01) and increased rates of additional procedures to control bleeding (aOR, 4.0 (95% CI, 1.3-11.9); P = 0.01). CONCLUSION: Despite high rates of resolution of low-lying placenta and placenta previa by term, women with resolved low placentation remain at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Reproductive factors and breast arterial calcification: a systematic review and meta-analysis.

BACKGROUND: Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS: MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS: Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS: BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO: CRD42020141644.

Early Prophylactic Gastrectomy for the Management of Gastric Adenomatous Proximal Polyposis Syndrome (GAPPS).

Background: Gastric adenomatous proximal polyposis syndrome (GAPPS) is a recently described, rare, autosomal dominant condition characterized by the extensive involvement of the proximal stomach with hundreds of heterogeneous fundic gland polyps with antral and duodenal sparing. GAPPS is caused by a point mutation of the APC gene promoter 1B and is associated with a risk of malignant transformation, distant metastasis, and death. There are no surveillance, screening, or treatment guidelines for managing GAPPS. The few reported cases have been variably managed with endoscopic surveillance or prophylactic gastrectomy. However, there is no consensus on the optimal management approach. Summary: In this case series, we review the relevant literature on GAPPS and present two siblings who underwent early prophylactic total gastrectomies with good outcomes. Conclusion: Due to the poor correlation between the endoscopic findings on sampled polyps and the risk of harboring invasive gastric cancer, patients with GAPPS should be strongly considered for early prophylactic total gastrectomies in the absence of prohibitive comorbidities.

Transient heating in fixed length optical cavities for use as temperature and pressure standards.

Optical refractometry techniques enable realization of both pressure and temperature directly from properties of the gas. The NIST refractometer, a fixed length optical cavity (FLOC) has previously been evaluated for operation as pressure standard, and now in this paper, is evaluated for the feasibility of operation as a primary temperature standard as well. The challenge is that during operation, one cavity is filled with gas. Gas dynamics predicts that this will result in heating which in turn will affect the cavity temperature uniformity, impeding the ability to measure the gas temperature with sufficient accuracy to make the standard useful as a primary standard for temperature or pressure. Temperature uniformity across the refractometer must be less than 0.5 mK for measurements of the refractivity to be sufficiently accurate for the FLOC. This paper compares computer modeling to laboratory measurements, enabling us to validate the model to predict thermal behavior and to accurately determine the measurement uncertainty of the technique. The results presented in this paper show that temperature of the glass elements of the refractometer and 'thermal-shell' copper chamber are equivalent to within 0.5 mK after an equilibration time of 3000 s (when going from 1 kPa to 100 kPa). This finding enables measurements of the copper chamber to determine the gas temperature to within an uncertainty (k = 1) of 0.5 mK. Additionally, the NIST refractometer is evaluated for feasibility of operation as temperature standard.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Normothermic ex vivo perfusion of the limb allograft depletes donor leukocytes prior to transplantation.

INTRODUCTION: The donor immune compartment plays a central role in graft rejection of the vascularised composite allograft (VCA) by contributing to 'direct presentation'. Using our limb ex vivo normothermic machine perfusion (EVNP) protocol designed for prolonged allograft preservation, this study aimed to assess whether donor leukocytes responsible for allograft rejection are mobilised from the donor compartment. METHODS: Five genetically different pig forelimbs underwent perfusion via the brachial and radial collateral artery for 6 h after 2 h of cold storage. Oxygenated haemodilute leucocyte-deplete blood was recirculated at normothermia using an extracorporeal perfusion system. Tissue perfusion was evaluated clinically and biochemically via blood perfusate. The temporal kinetics of donor leucocyte extravasation, cytokine secretion and cell-free DNA was characterised in the circulating perfusate. RESULTS: Flow cytometry revealed increasing populations of viable leukocytes over time, reaching 49 billion leukocytes by 6 h. T (3.0 × 109 cells) and B cells (3.1 × 108 cells) lymphocytes, monocytes (2.7 × 109 cells), granulocytes (8.1 × 109 cells), NK (6.3 × 108) and γδ (8.1 × 108) cells were all identified. Regulatory T cells comprised a minor population (1.6 × 107 cells). There was a cumulative increase in pro-inflammatory cytokines suggesting that the donor limb has the capacity to elicit significant inflammatory responses that could contribute to leucocyte activation and diapedesis. CONCLUSION: EVNP not only acts as a preservation tool, but could also be utilized to immunodeplete the VCA allograft prior to transplantation. This has clinical implications to mitigate acute rejection and prevent graft dysfunction and supports the future application of machine perfusion in graft preservation and immune modulation.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

Suspected cauda equina syndrome: no reduction in investigation, referral and treatment during the COVID-19 pandemic.

INTRODUCTION: Compression of the cauda equina can lead to bladder, bowel and sexual dysfunction with lower limb pain, numbness and weakness. Urgent surgical decompression aims to prevent progressive neurological deficit. Symptoms of cauda equina syndrome (CES), such as back pain, sciatica and bladder dysfunction are common in the population, but the majority of those investigated do not have radiological cauda equina compression. However, a missed diagnosis can have significant medical, social and legal consequences. We investigated the effect of the COVID-19 pandemic on presentation and management of suspected CES. METHODS: This retrospective cohort study analysed referral, investigation and treatment of CES in a regional neurosurgical centre during the initial COVID-19 surge between March and May 2020 compared with March to May 2019. RESULTS: Referrals for suspected CES were similar during the COVID-19 pandemic (n = 275) compared with 2019 (n = 261, p = 0.596) despite a significant (19%) decrease in total emergency neurosurgical referrals (1248 in 2020 vs 1544 in 2019, p < 0.001). Nineteen (7%) of the suspected CES referrals underwent decompression in 2020, similar to 16 (6%) in 2019 (p = 0.867). There were no differences in outcomes or complications and no evidence of delays in presentation or treatment. CONCLUSIONS: Unlike other emergency neurosurgical conditions, the number of referrals for suspected CES and the percentage of referrals with radiological cauda equina compression were unchanged during the COVID-19 pandemic. The persistence of CES referrals when many people stayed away from hospital highlights the distress and worry caused by suspected CES and its symptoms to both patients and healthcare providers.