A Novel Whole Tissue Explant Model of Hidradenitis Suppurativa.

Hidradenitis Suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to our relatively limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, and many patients' medical needs are not being met. This is partly due to a scarcity of ex vivo human assays and animal models that accurately recapitulate the disease. To address this deficit, we have developed a whole-tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar-media solution, finding that IL-6 and IL-8 concentrations trended upwards in both HS explants and healthy controls, while IL-17A, IL-1ß, and TNF-α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL-2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.

Chronic cannabis use associated with subcortical topological reorganization of structural connectivity in adults.

BACKGROUND: Cannabis is commonly used in the United States. However, chronic cannabis use has been linked to alterations in white matter (WM) integrity. Studies investigating WM in people who use cannabis (PWC) have produced varying results, which may be due to a variety of factors, including a focus on individual WM tracts. Here, we examined WM connectivity using a module-based approach to help clarify whether cannabis use is associated with differences in WM organization. METHODS: Connectomics is used to map complex networks of inter and intra-connected cortical and subcortical regions. A key concept of brain organization is the presence of groups of densely interconnected regions, referred to as modules. Here, we used WM structural connectivity estimates to compare connectome organization between adults who used cannabis regularly (n=53), and adults who did not use cannabis (n=60). We quantified aspects of network organization both across the whole brain and within specific modules. RESULTS: There were no significant results between groups after correcting for multiple comparisons for whole-brain metrics. When considering group differences in network organization metrics for 10 identified modules, we observed that adult PWC showed higher within-module degree, local efficiency, and network strength in a right subcortical module relative to adults that did not use cannabis. CONCLUSIONS: These results suggest that cannabis use in adults is associated with alterations of subcortical WM network organization. The observed differences in WM organization may be due to the involvement of the endocannabinoid system in the alteration of WM growth processes.

Uterine cancer restaging according to the updated 2023 FIGO Guidelines does not uniformly affect prognosis: An institutional retrospective cohort study.

OBJECTIVE: Efforts have been made to better risk stratify patients given the rise in incidence of endometrial cancer (EC). The 2023 FIGO staging now incorporates histologic subtype and molecular classification into determination of EC stage. We sought to elucidate if the new staging system demonstrated prognostic differences compared to the 2009 staging system. METHODS: A retrospective chart review was performed on women treated for EC at our institution from September 2013 to May 2023 and combined with the publicly available TCGA Nature 2013 dataset. Detailed clinical information was captured. Patients were restaged according to the 2023 guidelines. Survival estimates were obtained using Kaplan-Meier method, and the log-rank test was used to compare survival curves for progression-free survival (PFS). RESULTS: 919 patients were included in our analysis. The datasets were comparable regarding histologic grade, stage, and age at diagnosis. 175 (31.5%) of patients in the institution dataset and 115 (31.6%) patients in the TCGA dataset experienced a stage change. Most patients whose stage changed were upstaged (275/290; 94.8%). 3-year PFS estimates for stage IA patients with no stage change versus those upstaged were 92.3% (95% CI: 87.2, 95.4) v. 72.0% (95% CI: 68.4, 84.9), p = 0.002. No significant differences in survival difference were seen in other stage subsets. CONCLUSION: Modest survival differences exist in patients with EC originally staged as IA who underwent upstaging. No significant survival difference is observed in patients who are restaged to stage II or III subsets. Improved risk stratification is needed in assessing prognosis and adjuvant therapy for patients with endometrial cancer.

Salvage strategy for long-term central venous catheter-associated Staphylococcus aureus infections in children: a multi-centre retrospective study in France.

OBJECTIVES: Catheter removal is recommended in adults with Staphylococcus aureus central-line-associated bloodstream infection (CLABSI) but is controversial in children with long-term central venous catheters (LTCVC). We evaluated the occurrence of catheter salvage strategy (CSS) in children with S. aureus LTCVC-associated CLABSI and assessed determinants of CSS failure. METHODS: We retrospectively included children (<18 years) with an LTCVC and hospitalized with S. aureus CLABSI in eight French tertiary-care hospitals (2010-2018). CSS was defined as an LTCVC left in place ≥72 h after initiating empiric antibiotic treatment for suspected bacteraemia. Characteristics of patients were reviewed, and multi-variable logistic regression was performed to identify factors associated with CSS failure (i.e., persistence, recurrence or complications of bacteraemia). RESULTS: We included 273 episodes of S. aureus LTCVC-associated CLABSI. CSS was chosen in 194 out of 273 (71%) cases and failed in 74 of them (38%). The main type of CSS failure was the persistence of bacteraemia (39 of 74 cases, 53%). Factors independently associated with CSS failure were: history of catheter infection (adjusted odds ratio (aOR) 3.18, 95% confidence interval (CI) 1.38-7.36), CLABSI occurring on an implantable venous access device (aOR 7.61, 95% CI 1.98-29.20) when compared with tunnelled-cuffed CVC, polymicrobial CLABSI (aOR 3.45, 95% CI 1.25-9.50), and severe sepsis at the initial stage of infection (aOR 4.46, 95% CI 1.18-16.82). CONCLUSIONS: CSS was frequently chosen in children with S. aureus LTCVC-associated CLABSI, and failure occurred in one-third of cases. The identified risk factors may help clinicians identify children at risk for CSS failure.

Aggregatibacter actinomycetemcomitans infection in children: two case reports and a review of the literature.

Aggregatibacter actinomycetemcomitans (Aa), a Gram-negative coccobacillus commonly associated with endocarditis, poses a rare diagnostic challenge in pediatric cases. The presentation of two pediatric cases-myositis and chest mass-highlights novel aspects, including unusual symptom presentations in children which can be mistaken for malignancy. The limited sensitivity of standard blood tests complicates diagnosis, leading to delayed diagnosis and treatment. Representative samples must be taken, especially if blood cultures are negative. Despite advances in detection methods, diagnosing Aa infection remains difficult due to its rarity in children and variable clinical presentation. In conclusion, a comprehensive understanding of Aa infection in children is essential for early and effective diagnostic and therapeutic management.

Quantum control of a cat qubit with bit-flip times exceeding ten seconds.

Quantum bits (qubits) are prone to several types of error as the result of uncontrolled interactions with their environment. Common strategies to correct these errors are based on architectures of qubits involving daunting hardware overheads1. One possible solution is to build qubits that are inherently protected against certain types of error, so the overhead required to correct the remaining errors is greatly reduced2-7. However, this strategy relies on one condition: any quantum manipulations of the qubit must not break the protection that has been so carefully engineered5,8. A type of qubit known as a cat qubit is encoded in the manifold of metastable states of a quantum dynamical system, and thereby acquires continuous and autonomous protection against bit-flips. Here, in a superconducting-circuit experiment, we implemented a cat qubit with bit-flip times exceeding 10 s. This is an improvement of four orders of magnitude over previously published cat-qubit implementations. We prepared and imaged quantum superposition states, and measured phase-flip times greater than 490 ns. Most importantly, we controlled the phase of these quantum superpositions without breaking the bit-flip protection. This experiment demonstrates the compatibility of quantum control and inherent bit-flip protection at an unprecedented level, showing the viability of these dynamical qubits for future quantum technologies.

Comparison between moyamoya disease and moyamoya syndrome in Israel.

BACKGROUND AND AIMS: Moyamoya is a chronic brain vasculopathy involving the distal intracranial internal carotid artery (ICA) or proximal middle cerebral artery (MCA). Moyamoya patients can be divided into those with primary moyamoya disease (MMD) and those with moyamoya secondary to other known causes such as intracranial atherosclerosis (moymoya syndrome [MMS]). Our aim was to compare the characteristics of MMD patients to those of MMS patients in a sample of Israeli patients seen over the course of 20 years at a tertiary referral center. METHODS: Included patients were diagnosed with either MMD or MMS based on typical imaging findings and the presence or absence of known concomitant vascular risk factors or associated disorders and vascular disease. Patients with MMS were compared to those with MMD. Demographics, symptoms, signs, and radiological data were compared between the groups. Treatment options and long-term rates of recurrent stroke and functional outcome were also studied. RESULTS: Overall, 64 patients were included (25 MMD, 39 MMS). Patients with MMD were significantly younger (median IQR 20 (7-32) vs. 40 (19-52); p=0.035). Patients with MMS more often had vascular risk factors but there were no significant differences in clinical presentations or long-term disability rates between the groups and a similar proportion of patients underwent surgical interventions to restore hemispheric perfusion in both groups (48% vs. 44% MMS vs. MMD; p=0.7). Almost one in four patient had a recurrent stroke after the initial diagnosis in both groups. Most recurrences occurred in the pre-surgery period in the MMS group and in the post-surgery period in the MMD group. CONCLUSIONS: There were no statistically significant differences in clinical or radiological presentations between the MMS and MMD patients. The course is not benign with recurrent stroke occurring in as many as 25%. More data is needed in order to identify those at high risk for stroke occurrence and recurrence.

Liposomal bupivacaine versus conventional anesthetic or placebo for hemorrhoidectomy: a systematic review and meta-analysis.

BACKGROUND: Liposome bupivacaine (LB) is a long-acting anesthetic to enhance postoperative analgesia. Studies evaluating the efficacy of the LB against an active comparator (bupivacaine or placebo) on acute postoperative pain control in hemorrhoidectomy procedures are few and heterogeneous. Therefore, we performed a systematic review and meta-analysis comparing LB's analgesic efficacy and side effects to conventional/placebo anesthetic in hemorrhoidectomy patients. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials investigating the use of LB after haemorrhoidectomy. We searched the literature published from the time of inception of the datasets to August 19, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus. RESULTS: A total of 338 patients who underwent a hemorrhoidectomy procedure enrolled in three randomized clinical trials were included. The overall mean age was 45.84 years (SD ± 11.43), and there was a male predominance (53.55% male). In total 194 patients (52.2%) received LB and 144 (47.8%) received either bupivacaine or placebo. Pain scores at 72 h in the LB (199, 266, and 300 mg) were significantly lower than in the bupivacaine HCl group (p = 0.002). Compared to the bupivacaine/placebo group, the time to first use of opioids in the LB group was significantly longer at LB 199 mg (11 h vs. 9 h), LB 266 mg (19 h vs. 9 h), and LB 300 mg (19 h vs. 8 h) (p < 0.05). Moreover, compared to the bupivacaine/epinephrine group, it was significantly lower in the LB 266 mg group (3.7 vs. 10.2 mg) and at LB 300 mg (13 vs. 33 mg) (p < 0.05). Finally, regarding adverse effects, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups (OR 2.60, 95% CI 1.31-5.16). CONCLUSIONS: Comparing LB to conventional anesthetic/placebo anesthetic for hemorrhoidectomy, we found a statistically significant reduction in pain through 72 h, decreased opioid requirements, and delayed time to first opioid use. Moreover, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups.

The incremental risk of fragility fractures in aging men.

INTRODUCTION: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population. METHODS: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata. RESULTS: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001). CONCLUSION: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality.

Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Effects of tumor type on outcomes in patients with large vessel occlusion stroke and cancer.

BACKGROUND: Large vessel occlusions (LVO) stroke is associated with cancer. Whether this association differs among patients with LVO that undergo endovascular thrombectomy (EVT) according to cancer type remains unknown. PATIENTS AND METHODS: Data from consecutive patients that underwent EVT for LVO at three academic centers were pulled and analyzed retrospectively. Patients with LVO and solid tumors were compared to those with hematological tumors. Associations of cancer type with 90-day functional outcome and mortality were calculated in multivariable analyses. RESULTS: Of the 154 patients with cancer and LVO that underwent EVT (mean age 74±11, 43% men, median NIHSS 15), 137 had solid tumors (89%) and 17 (11%) had hematologic tumors. Patients with solid cancer did not significantly differ from those with hematological malignancy in demographics, risk factor profile, stroke severity and subtype, and procedural variables. Outcome parameters including rates of favorable target recanalization and favorable outcome or mortality at discharge and 90 days post stroke were similar. Safety parameters including rates of symptomatic intracranial hemorrhage also did not differ between the groups. On regression analyses, controlling for various prognostic variables cancer type was not associated with mortality or favorable outcomes. CONCLUSIONS: Our study suggests that the safety and efficacy of EVT in patients with malignancy does not depend on cancer type. Patients with malignancy should be considered for EVT regardless of cancer type.

Reflections of maternity service users and midwives' on the co-creation of interventions to support midwives addressing alcohol during antenatal care.

BACKGROUND: There are divergent perspectives between midwives and pregnant women on how alcohol consumption during pregnancy could be addressed. Co-creation is an approach where lay people and professionals work together as equal partners, offering the opportunity to bridge the gap. OBJECTIVES: Our aim was to evaluate how well we carried out authentic co-creation of an intervention to support midwives have a dialogue about alcohol consumption with pregnant women. PATIENT INVOLVEMENT: Recent maternity service users including women with experience of harm due to alcohol during pregnancy provided feedback on the design, conduct and dissemination of the study. METHODS: An iterative co-creation approach rooted in participatory research methods was used. Five online workshops were carried out with thirteen midwives and six maternity service users via Zoom July-August 2021. Data were analysed using the core values of co-create as a framework: equality, inclusivity, holistic, resource, positivity, transparency, iterative, and sustainability. RESULTS: The co-creation process was productive and rewarding to midwives and maternity service users. There were positive experiences across the co-creation framework with some unintended positive consequences for maternity-service users. DISCUSSION: This evaluation provides new knowledge on how well the co-creation process worked in relation to research involving a sensitive topic that can invite stigma. Co-creation projects require generous time and financial resources to ensure a high-quality process and robust outcome for all. PRACTICAL VALUE: Co-creation of strategies involving both service providers and service users have potential to facilitate evidence-based practice. FUNDING: This research is funded by the National Institute for Health Research (Reference: NIHR201128).

Clinical utility of repeat fetal echocardiography in congenital heart disease.

OBJECTIVES: To investigate the utility of repeat fetal echocardiography (FE) following a diagnosis of structural congenital heart disease (CHD) on the initial FE. We evaluated how often changes in management and counseling occurred based on subsequent FE findings and sought to determine which types of CHD were more likely to have changes in management and/or counseling based on repeat FE. METHODS: This was a retrospective review of all patients who presented to our center between January 2012 and January 2019 and who had more than one FE performed for structural CHD. We reviewed consultation notes to determine whether management or counseling had changed based on FE findings at follow-up visits. Management variables included a change in location or mode of delivery, plan for atrial septostomy, initiation of prostaglandin infusion, umbilical line placement and planned admission location (nursery vs neonatal intensive care unit). We defined a counseling change as any of the above changes in management as well as any meaningful refinements in the cardiac diagnosis that led to a change in the overall prognosis or future management. Initial diagnoses were grouped into anatomically/hemodynamically relevant subgroups. Fisher's exact test was used to assess the relationship between the initial diagnosis and changes in management. Post-hoc pairwise comparisons were performed using Dunnett's test. RESULTS: Between January 2012 and January 2019, 267 patients underwent 534 follow-up FE assessments performed for structural CHD. Management change based on repeat FE occurred in 41/267 (15.4%) cases. A change in management was associated with the diagnosis made at the initial visit (P < 0.001). The proportion of cases with a management change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (4/11 (36.4%)), followed by balanced atrioventricular canal (AVC) defect (5/17 (29.4%)) and left ventricular outflow tract obstruction/aortic valve abnormality or coarctation/interrupted aortic arch (19/68 (27.9%)). No management change occurred in fetuses diagnosed with isolated ventricular septal defect (VSD), truncus arteriosus, pulmonary vein anomaly or isolated arch sidedness/branching abnormality. Compared to those with a VSD, management was significantly more likely to be changed in fetuses with a balanced AVC defect (P = 0.025) and left heart lesions (P = 0.002). Right heart lesions showed a trend towards an increased incidence of management change (P = 0.05). A counseling change based on repeat FE occurred in 108/267 (40.4%) cases. The proportion of cases with a counseling change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (8/11 (72.7%)) and hypoplastic left heart syndrome/critical aortic stenosis (5/9 (55.6%)). CONCLUSIONS: The clinical utility of follow-up FE is associated with the type of CHD diagnosed. Follow-up FE led to changes in management in several types of CHD, most commonly in cases with an initial diagnosis of right and left outflow obstructive lesions and balanced AVC defect. When developing programmatic protocols for the frequency of FE assessments, the type of CHD should be a major determinant, but additional studies are required to reach a consensus on how often serial FE should be performed for each type of CHD. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Patterns of endocardial fibroelastosis without atrioventricular block in fetuses exposed to anti-Ro/SSA antibodies.

Anti-Ro/SSA-antibody-mediated endocardial fibroelastosis (EFE) without atrioventricular (AV) block at presentation is a rare cardiac phenotype. We report on 11 fetuses with this rare type of anti-Ro/SSA-antibody-mediated cardiac involvement, presenting with a distinctive echocardiographic pattern of EFE. Eleven fetuses with isolated EFE at presentation were included from four cardiac centers, and experienced fetal cardiologists reached a consensus regarding EFE location on echocardiography at presentation. Interval changes to subsequent fetal and postnatal echocardiograms were assessed to evaluate response to therapy. Echocardiographic markers of cardiac performance, including diastolic function and AV conduction, were reviewed. Ten fetuses were found to have EFE of the aortic root, proximal aorta and/or left ventricular outflow tract. In the same 10 cases, EFE of the pulmonary root, pulmonary artery and/or right ventricular outflow tract was identified. Six cases had atrial EFE and six had EFE of the crux. Four cases were known to be positive for anti-Ro/SSA antibodies prior to diagnosis, whereas, in the remaining seven, echocardiographic findings prompted testing, which was positive in all cases. The AV interval at presentation was normal in all cases, but one fetus subsequently developed AV block. Nine patients were treated with transplacental dexamethasone, five of which also received intravenous immunoglobulin (IVIG), and one received IVIG only. Of the 10 treated cases, six had improvement in EFE as shown by serial imaging and, in four cases, the severity was unchanged. All patients were liveborn. In our cohort, EFE of the aortic and pulmonary arteries and outflow tracts was nearly universal, and involvement of the atria and the crux of the heart was also common. The high survival rate and low burden of AV block are also suggestive of a distinct phenotype of anti-Ro/SSA-antibody-mediated cardiac disease with a favorable prognosis. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of postnatal circulation in pulmonary atresia/critical stenosis with intact ventricular septum: systematic review and external validation of models.

OBJECTIVE: A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort. METHODS: This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated. RESULTS: Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models. CONCLUSIONS: Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Covid-19 associated free hanging clots in acute symptomatic carotid stenosis.

BACKGROUND: Thrombotic complications including stroke were previously described following Covid-19. We aim to describe the clinical and radiological characteristics of Covid-19 related with acutely symptomatic carotid stenosis (aSCS). METHOD: All patients presenting with an aSCS were prospectively enrolled in an ongoing institutional database. Inclusion criteria for the Covid-19-aSCS group were a combination of both antigen test and a positive reverse-transcriptase (PCR) test for Covid-19 upon admission. Patients with additional potential etiologies for stroke including cardioembolism, carotid dissection or patients with stenosis of <50% on CTA were excluded. A cohort of non-Covid-19 related aSCS patients admitted to the same institution before the pandemic during 2019 served as controls. RESULTS: Compared to controls (n = 31), Covid-19-aSCS (n = 8), were younger (64.2 ± 10.7 vs 73.5 ± 10, p = 0.027), and less frequently had hypertension (50% vs 90%, p = 0.008) or hyperlipidemia (38% vs 77%, p = 0.029) before admission. Covid-19-aSCS patients had a higher admission NIHSS score (mean 9 ± 7 vs 3 ± 4, p = 0.004) and tended to present more often with stroke (88% vs 55%, p = 0.09) rather than a TIA. Covid-19-aSCS patients had higher rates of free-floating thrombus and clot burden on CTA (88% vs 6.5%, p = 0.002). Covid-19 patients also less often achieved excellent outcomes, with lower percentage of mRS score of 0 after 90-days (13% vs 58%, p = 0.022). CONCLUSION: Covid-19- aSCS may occur in a younger and healthier subpopulation. Covid-19- aSCS patients may have higher tendencies for developing complex clots and less often achieve excellent outcomes.

Co-designed weight management intervention for women recovering from oestrogen-receptor positive breast cancer.

BACKGROUND: Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, particularly in women with oestrogen receptor-positive (ER +) disease. The aim of this study was to co-design (with patients) a programme of tailored, personalised support (intervention), including high-quality support materials, to help female breast cancer patients (BCPs) with ER + disease to develop the skills and confidence needed for sustainable weight loss.  METHODS: ER + BCPs were recruited from two UK National Health Service (NHS) Trusts. The selection criteria included (i) recent experience of breast cancer treatment (within 36 months of completing primary treatment); (ii) participation in a recent focus group study investigating weight management perceptions and experiences; (iii) willingness to share experiences and contribute to discussions on the support structures needed for sustainable dietary and physical activity behaviour change. Co-design workshops included presentations and interactive activities and were facilitated by an experienced co-design researcher (HH), assisted by other members of the research team (KP, SW and JS). RESULTS: Two groups of BCPs from the North of England (N = 4) and South Yorkshire (N = 5) participated in a two-stage co-design process. The stage 1 and stage 2 co-design workshops were held two weeks apart and took place between Jan-March 2019, with each workshop being approximately 2 h in duration. Guided by the Behaviour Change Wheel, a theoretically-informed weight management intervention was developed on the basis of co-designed strategies to overcome physical and emotional barriers to dietary and physical activity behaviour change. BCPs were instrumental in designing all key features of the intervention, in terms of Capability (e.g., evidence-based information, peer-support and shared experiences), Opportunity (e.g., flexible approach to weight management based on core principles) and Motivation (e.g., appropriate use of goal-setting and high-quality resources, including motivational factsheets) for behaviour change. CONCLUSION: This co-design approach enabled the development of a theoretically-informed intervention with a content, structure and delivery model that has the potential to address the weight management challenges faced by BCPs diagnosed with ER + disease. Future research is required to evaluate the effectiveness of the intervention for eliciting clinically-important and sustainable weight loss in this population.

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions.

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.