Engineered heart tissue: Design considerations and the state of the art.

Originally developed more than 20 years ago, engineered heart tissue (EHT) has become an important tool in cardiovascular research for applications such as disease modeling and drug screening. Innovations in biomaterials, stem cell biology, and bioengineering, among other fields, have enabled EHT technologies to recapitulate many aspects of cardiac physiology and pathophysiology. While initial EHT designs were inspired by the isolated-trabecula culture system, current designs encompass a variety of formats, each of which have unique strengths and limitations. In this review, we describe the most common EHT formats, and then systematically evaluate each aspect of their design, emphasizing the rational selection of components for each application.

Differential responses to cigarette package labeling alternatives among adults who smoke: Results from a randomized trial.

INTRODUCTION: Little experimental research has evaluated whether the effects of cigarette package inserts with efficacy messages and/or pictorial health warning labels (PHWLs) differ across key subgroups of adults who smoke. METHODS: Adults who reported currently smoking (n=367) were randomly assigned to one of four groups: small text-only health warning labels (HWLs) on pack sides (control); inserts with efficacy messages and small HWLs (inserts-only); PHWLs showing harms of smoking (PHWLs-only); both (inserts+PHWLs). Participants received a 14-day supply of cigarettes labeled to reflect their group. Every evening over two weeks, participants reported forgoing and stubbing out cigarettes before they finished smoking over the prior 24 hours, combined into a binary indicator of either behavior (e.g., forgoing/stubbing). Separate mixed-effects logistic models were estimated to evaluate moderation of labeling group contrasts (i.e., PHWLs vs not; inserts vs. not; inserts-only vs. inserts+PHWLs; PHWLs-only vs. inserts+PHWLs) by baseline covariates (self-efficacy to quit, intention to quit, education, health literacy, time discounting), predicting day-level forgoing/stubbing. RESULTS: Education moderated PHWL effects, with PHWLs predicting more forgoing/stubbing only among those with low education (OR=4.68, p<0.001). Time discounting moderated insert effects, with inserts promoting fogoing/stubbing only among those with low time discounting (i.e., lower impulsivity; OR=4.35, p<0.001). CONCLUSIONS: Inserts with efficacy messages appear effective mostly among people with low time discounting, whereas PHWLs appear most effective amongst those with low education, suggesting their potential to address education-related disparities. Labeling strategies appeared equally effective across subgroups defined by self-efficacy to quit, quit intention, and health literacy. Combining inserts with PHWLs did not appear to mitigate moderation effects. IMPLICATIONS: This randomized trial with adults who smoke suggests that cigarette packs with inserts describing cessation benefits and tips can promote cessation-related behaviors (i.e., forgoing or stubbing out cigarettes) among those with low time discounting (i.e., low impulsivity). Alternative interventions may be needed for people with high time discounting, as found in cessation trials. Pictorial health warning labels (PHWLs) appear most effective among those with low education, potentially addressing education-related disparities. No differential effects were found for those with different levels of self-efficacy to quit, quit intentions, or health literacy. Combining inserts and PHWLs may not be more effective than either alone.

Does proactive care in care homes improve survival? A quality improvement project.

BACKGROUND: NHS England's 'Enhanced Health in Care Homes' specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches vary widely: challenges include frailty identification, multidisciplinary team (MDT) capability/capacity and how the process is structured and delivered. AIM: To determine whether a proactive healthcare model could improve healthcare outcomes for care home residents. DESIGN AND SETTING: Quality improvement project involving 429 residents in 40 care homes in a non-randomised crossover cohort design. The headline outcome was 2-year survival. METHOD: All care home residents had healthcare coordinated by the PCN's Older Peoples' Hub. A daily MDT managed the urgent healthcare needs of residents. Proactive healthcare, comprising information technology-assisted comprehensive geriatric assessment (i-CGA) and advanced care planning (ACP), were completed by residents, with prioritisation based on clinical needs.Time-dependent Cox regression analysis was used with patients divided into two groups:Control group: received routine and urgent (reactive) care only.Intervention group: additional proactive i-CGA and ACP. RESULTS: By 2 years, control group survival was 8.6% (n=108), compared with 48.1% in the intervention group (n=321), p<0.001. This represented a 39.6% absolute risk reduction in mortality, 70.2% relative risk reduction and the number needed to treat of 2.5, with little changes when adjusting for confounding variables. CONCLUSION: A PCN with an MDT-hub offering additional proactive care (with an i-CGA and ACP) in addition to routine and urgent/reactive care may improve the 2-year survival in older people compared with urgent/reactive care alone.

Self-reported attention and responses to cigarette package labels at the end of a two-week randomized trial of cigarette package labeling configurations.

INTRODUCTION: Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including potentially enhancing the effects of pictorial health warning labels (PHWLs). METHODS: A randomized trial with a 2×2 factorial design was conducted with adult smokers (n=356) assigned to either small text-only health warning labels (HWLs; control); inserts with cessation messages, and the small text-only HWLs (inserts-only); large PHWLs (PHWLs-only); both inserts and PHWLs (inserts + PHWLs). Participants received a 14-day supply of their preferred cigarettes with packs labeled to reflect their group. Upon finishing the trial, participants reported their past 14-day frequency of noticing, reading, thinking about smoking harms and cessation benefits, talking about labels, and forgoing cigarettes because of the labels. Ordered logistic models regressed these outcomes on labeling groups, and mediation analyses assessed whether attention (i.e. noticing, reading) to labels mediated effects of labeling exposure on other outcomes (i.e. thinking about harms/benefits, talking, forgoing). RESULTS: The inserts + PHWLs group reported higher frequencies than the control group for all outcomes. Compared to the control group, both the inserts-only and PHWLs-only groups reported higher frequency of noticing (AOR=3.53 and 2.46, respectively) and reading labels (AOR=2.89 and 1.71), thinking about smoking risks because of the labels (AOR=1.93 and 1.82), and talking about labels (AOR=2.30 and 2.70). Participants in the inserts-only group also reported more frequent thinking about quitting benefits (AOR=1.98). Attention mediated all labeling effects except for the contrast between PHWLs only and control. CONCLUSIONS: Compared to text-only HWLS, cigarette labeling that involves inserts, PHWLs, or both appears more effective at drawing attention to warnings, which mediated the effects on cessation-related psychosocial and behavioral outcomes.

What guidance exists to support patient partner compensation practices? A scoping review of available policies and guidelines.

BACKGROUND: An integral aspect of patient engagement in research, also known as patient and public involvement, is appropriately recognising patient partners for their contributions through compensation (e.g., coauthorship, honoraria). Despite known benefits to compensating patient partners, our previous work suggested compensation is rarely reported and researchers perceive a lack of guidance on this issue. To address this gap, we identified and summarised available guidance and policy documents for patient partner compensation. METHODS: We conducted this scoping review in accordance with methods suggested by the JBI. We searched the grey literature (Google, Google Scholar) in March 2022 and Overton (an international database of policy documents) in April 2022. We included articles, guidance or policy documents regarding the compensation of patient partners for their research contributions. Two reviewers independently extracted and synthesised document characteristics and recommendations. RESULTS: We identified 65 guidance or policy documents. Most documents were published in Canada (57%, n = 37) or the United Kingdom (26%, n = 17). The most common recommended methods of nonfinancial compensation were offering training opportunities to patient partners (40%, n = 26) and facilitating patient partner attendance at conferences (38%, n = 25). The majority of guidance documents (95%) suggested financially compensating (i.e., offering something of monetary value) patient partners for their research contributions. Across guidance documents, the recommended monetary value of financial compensation was relatively consistent and associated with the role played by patient partners and/or specific engagement activities. For instance, the median monetary value for obtaining patient partner feedback (i.e., consultation) was $19/h (USD) (range of $12-$50/h). We identified several documents that guide the compensation of specific populations, including youth and Indigenous peoples. CONCLUSION: Multiple publicly available resources exist to guide researchers, patient partners and institutions in developing tailored patient partner compensation strategies. Our findings challenge the perception that a lack of guidance hinders patient partner financial compensation. Future efforts should prioritise the effective implementation of these compensation strategies to ensure that patient partners are appropriately recognised. PATIENT OR PUBLIC CONTRIBUTIONS: The patient partner coauthor informed protocol development, identified data items, and interpreted findings.

Selective Thermal Deprotection of N-Boc Protected Amines in Continuous Flow.

Thermal N-Boc deprotection of a range of amines is readily effected in continuous flow, in the absence of an acid catalyst. While the optimum results were obtained in methanol or trifluoroethanol, deprotection can be effected in a range of solvents of different polarities. Sequential selective deprotection of N-Boc groups has been demonstrated through temperature control, as exemplified by effective removal of an aryl N-Boc group in the presence of an alkyl N-Boc group. As a proof of principle, a telescoped sequence involving selective deprotection of an aryl N-Boc group from 9h followed by benzoylation and deprotection of the remaining alkyl N-Boc group to form amide 13 proved successful.

Changes in Oxidised Phospholipids in Response to Oxidative Stress in Microtubule-Associated Protein Tau (MAPT) Mutant Dopamine Neurons.

Microtubule-associated protein Tau (MAPT) is strongly associated with the development of neurodegenerative diseases. In addition to driving the formation of neurofibrillary tangles (NFT), mutations in the MAPT gene can also cause oxidative stress through hyperpolarisation of the mitochondria. This study explores the impact that MAPT mutation is having on phospholipid metabolism in iPSC-derived dopamine neurons, and to determine if these effects are exacerbated by mitochondrial and endoplasmic reticulum stress. Neurons that possessed a mutated copy of MAPT were shown to have significantly higher levels of oxo-phospholipids (Oxo-PL) than wild-type neurons. Oxidation of the hydrophobic fatty acid side chains changes the chemistry of the phospholipid leading to disruption of membrane function and potential cell lysis. In wild-type neurons, both mitochondrial and endoplasmic reticulum stress increased Oxo-PL abundance; however, in MAPT mutant neurons mitochondrial stress appeared to have a minimal effect. Endoplasmic reticulum stress, surprisingly, reduced the abundance of Oxo-PL in MAPT mutant dopamine neurons, and we postulate that this reduction could be modulated through hyperactivation of the unfolded protein response and X-box binding protein 1. Overall, the results of this study contribute to furthering our understanding of the regulation and impact of oxidative stress in Parkinson's disease pathology.

What is the volume, quality and characteristics of evidence relating to the effectiveness and cost-effectiveness of multi-disciplinary occupational health interventions aiming to improve work-related outcomes for employed adults? An evidence and gap map of systematic reviews.

Background: In the UK, tens of millions of working days are lost due to work-related ill health every year, costing billions of pounds. The role of Occupational Health (OH) services is vital in helping workers to maintain employment when they encounter injury or illness. OH providers traditionally rely on a clinical workforce to deliver these services, particularly doctors and nurses with OH qualifications. However, the increasing demand for OH services is unlikely to be met in the future using this traditional model, due to the declining number of OH-trained doctors and nurses in the UK. Multi-disciplinary models of OH delivery, including a more varied range of healthcare and non-healthcare professionals, could provide a way to meet this new demand for OH services. There is a need to identify collaborative models of OH service delivery and review their effectiveness on return-to work outcomes. There is an existing pool of systematic review evidence evaluating workplace based, multi-disciplinary OH interventions, but it is difficult to identify which aspects of the content and/or delivery of these interventions may be associated with improved work-related outcomes. Objectives: The aim of this evidence and gap map (EGM) was to provide an overview of the systematic review evidence that evaluates the effectiveness and cost-effectiveness of multi-disciplinary OH interventions intending to improve work-related outcomes. Search Methods: In June 2021 we searched a selection of bibliographic databases and other academic literature resources covering a range of relevant disciplines, including health care and business studies, to identify systematic review evidence from a variety of sectors of employment. We also searched Google Search and a selection of topically relevant websites and consulted with stakeholders to identify reports already known to them. Searches were updated in February 2023. Selection Criteria: Systematic reviews needed to be about adults (16 years or over) in employment, who have had absence from work for any medical reason. Interventions needed to be multi-disciplinary (including professionals from different backgrounds in clinical and non-clinical professions) and designed to support employees and employers to manage health conditions in the workplace and/or to help employees with health conditions retain and/or return to work following medical absence. Effectiveness needed to be measured in terms of return to work, work retention or measures of absence, or economic evaluation outcomes. These criteria were applied to the title and abstract and full text of each systematic review independently by two reviewers, with disagreements resolved through discussion. We awarded each systematic review a rating of 'High', 'Medium' or 'Low' relevance to indicate the extent to which the populations, interventions and their contexts synthesised within the review were consistent with our research question. We also recorded the number of primary studies included within each of the 'High' and 'Medium' reviews that were relevant to research question using the same screening process applied at review level. Data Collection and Analysis: Summary data for each eligible review was extracted. The quality of the systematic reviews, rated as 'High' or 'Medium' relevance following full text screening, was appraised using the AMSTAR-2 quality appraisal tool. All data were extracted by one reviewer and checked by a second, with disagreements being settled through discussion. Summary data for all eligible systematic reviews were tabulated and described narratively. The data extracted from reviews of 'High' and 'Medium' relevance was imported into EPPI-Mapper software to create an EGM. Stakeholder Involvement: We worked alongside commissioners and policy makers from the Department of Health and Social Care (DHSC) and Department of Work and Pensions (DWP), OH personnel, and people with lived experience of accessing OH services themselves and/or supporting employees to access OH services. Individuals contributed to decision making at all stages of the project. This ensured our EGM reflects the needs of individuals who will use it. Main Results: We identified 98 systematic reviews that contained relevant interventions, which involved a variety of professionals and workplaces, and which measured effectiveness in terms of return to work (RTW). Of these, we focused on the 30 reviews where the population and intervention characteristics within the systematic reviews were considered to be of high or medium relevance to our research questions. The 30 reviews were of varying quality, split evenly between High/Moderate quality and Low/Critically-Low quality ratings. We did not identify any relevant systematic review evidence on any other work-related outcome of interest. Interventions were heterogenous, both within and across included systematic reviews. The EGM is structured according to the health condition experienced by participants, and the effectiveness of the interventions being evaluated, as reported within the included systematic reviews. It is possible to view (i) the quality and quantity of systematic review evidence for a given health condition, (ii) how review authors assessed the effectiveness or cost-effectiveness of the interventions evaluated. The EGM also details the primary studies relevant to our research aim included within each review. Authors' Conclusions: This EGM map highlights the array of systematic review evidence that exists in relation to the effectiveness or cost-effectiveness of multi-disciplinary, workplace-based OH interventions in supporting RTW. This evidence will allow policy makers and commissioners of services to determine which OH interventions may be most useful for supporting different population groups in different contexts. OH professionals may find the content of the EGM useful in identifying systematic review evidence to support their practice. The EGM also identifies where systematic review evidence in this area is lacking, or where existing evidence is of poor quality. These may represent areas where it may be particularly useful to conduct further systematic reviews.

Development of EBV Related Diffuse Large B-cell Lymphoma in Deficiency of Adenosine Deaminase 2 with Uncontrolled EBV Infection.

Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear.

Rapid spread of the SARS-CoV-2 JN.1 lineage is associated with increased neutralization evasion.

In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.

Barriers to smoking interventions in community healthcare settings: a scoping review.

Smoking is one of the major causes of preventable death and is considered the greatest threat to global public health. While the prevalence of smoking has decreased, population growth has led to an increase in the absolute number of smokers. There are many proven smoking cessation interventions available to support smokers in their quit attempts. Most people who smoke, however, underutilize the treatments available to them. This scoping review aimed to identify the current barriers experienced by all stakeholders (smokers, service providers and policymakers) to existing evidence-based smoking cessation interventions in community healthcare settings. Five electronic databases (CINAHL, Ovid MEDLINE, PsycINFO, Scopus and Web of Science) were searched for relevant literature. A total of 40 eligible articles from different countries published between 2015 and 2022 were included in the review and content analysis carried out to identify the key barriers to smoking cessation interventions. Seven key themes were found to be common to all stakeholders: (i) literacy, (ii) competing demands and priorities, (iii) time, (iv) access to product, (v) access to service, (vi) workforce and (vii) motivation/readiness. These themes were mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. This study presents the effect the barriers within these themes have on current smoking cessation services and highlights priorities for future interventions.

Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection.

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+ T cells, PD-1, and TIM-3 expression on CD4+ and CD8+ T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-ß, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

The Ottawa Statement implementation guidance document for cluster randomized trials in the hemodialysis setting.

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.

Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Role of IL-27 in Epstein-Barr virus infection revealed by IL-27RA deficiency.

Epstein-Barr virus (EBV) infection can engender severe B cell lymphoproliferative diseases1,2. The primary infection is often asymptomatic or causes infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder3. Selective vulnerability to EBV has been reported in association with inherited mutations impairing T cell immunity to EBV4. Here we report biallelic loss-of-function variants in IL27RA that underlie an acute and severe primary EBV infection with a nevertheless favourable outcome requiring a minimal treatment. One mutant allele (rs201107107) was enriched in the Finnish population (minor allele frequency = 0.0068) and carried a high risk of severe infectious mononucleosis when homozygous. IL27RA encodes the IL-27 receptor alpha subunit5,6. In the absence of IL-27RA, phosphorylation of STAT1 and STAT3 by IL-27 is abolished in T cells. In in vitro studies, IL-27 exerts a synergistic effect on T-cell-receptor-dependent T cell proliferation7 that is deficient in cells from the patients, leading to impaired expansion of potent anti-EBV effector cytotoxic CD8+ T cells. IL-27 is produced by EBV-infected B lymphocytes and an IL-27RA-IL-27 autocrine loop is required for the maintenance of EBV-transformed B cells. This potentially explains the eventual favourable outcome of the EBV-induced viral disease in patients with IL-27RA deficiency. Furthermore, we identified neutralizing anti-IL-27 autoantibodies in most individuals who developed sporadic infectious mononucleosis and chronic EBV infection. These results demonstrate the critical role of IL-27RA-IL-27 in immunity to EBV, but also the hijacking of this defence by EBV to promote the expansion of infected transformed B cells.

Advances in Pharyngeal Surgery Over the Past 10 Years: New Techniques and Technology.

This article is a review of advances in pharyngeal surgery over the past 10 years regarding literature, surgical technique, assessment, collaboration, and future direction in the management of adult and pediatric obstructive sleep apnea.

Performance of VI-RADS in predicting muscle-invasive bladder cancer after transurethral resection: a single center retrospective analysis.

PURPOSE: To assess VIRADS performance and inter-reader agreement for detecting muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumor (TURBT). METHODS: An IRB-approved, HIPAA-compliant, retrospective study from 2016 to 2020 included patients with bladder urothelial carcinoma who underwent MRI after TURBT, and cystectomy within 3 months without post-MRI treatments. Three radiologists blinded to pathology results independently reviewed MR images and assigned a VI-RADS score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI-RADS were assessed for diagnosing MIBC using VI-RADS scores ≥ 3 and ≥ 4. Inter-reader agreement was assessed using Gwet's agreement coefficient (AC) and percent agreement. RESULTS: The cohort consisted of 70 patients (mean age, 68 years ± 11 [SD]; range 39-85; 58 men) and included 32/70 (46%) with MIBC at cystectomy. ROC analysis revealed an AUC ranging from 0.67 to 0.77 and no pairwise statistical difference between readers (p-values, 0.06, 0.08, 0.97). Percent sensitivity, specificity, PPV, NPV and accuracy for diagnosing MIBC for the three readers ranged from 81.3-93.8, 36.8-55.3, 55.6-60.5, 77.3-87.5, and 62.9-67.1 respectively for VI-RADS score ≥ 3, and 78.1-81.3, 47.4-68.4, 55.6-67.6, 72.0-78.8 and 61.4-72.9 respectively for VI-RADS score ≥ 4. Gwet's AC was 0.63 [95% confidence interval (CI): 0.49,0.78] for VI-RADS score ≥ 3 with 79% agreement [95% CI 72,87] and 0.54 [95%CI 0.38,0.70] for VI-RADS score ≥ 4 with 76% agreement [95% CI 69,84]. VIRADS performance was not statistically different among 31/70 (44%) patients who received treatments prior to MRI (p ≥ 0.16). CONCLUSION: VI-RADS had moderate sensitivity and accuracy but low specificity for detection of MIBC following TURBT, with moderate inter-reader agreement.

Transitioning from interventional radiology: ideas for the inevitable.

BACKGROUND: Interventional Radiology (IR) is a highly rewarding specialty, both for its salutary effects for patients, as will as the satisfaction it provides for the operating radiologists. Nonetheless, arduous work and long hours have led to numerous reports of burnout amongst interventional radiologists (IRs). MATERIALS AND METHODS: Six long-term academic radiologists in leadership positions briefly chronicle their becoming IRs, their type of transitioning from IR, and the pros and cons of those respective transitions. RESULTS: The specific transitions include reduced time in IR, switching to diagnostic radiology, becoming involved in medical school education, ceasing IR leadership, and retirement. Pros and cons of the various transition strategies are highlighted. CONCLUSION: As the taxing work and long hours are so ubiquitous for IRs, and as burnout is so common, transitioning from IR is highly likely eventually for IRs. The varied transition experiences highlighted in this report hopefully will be helpful for current and aspiring IRs.

Clinical indications, safety, and effectiveness of percutaneous image-guided adrenal mass biopsy: an 8-year retrospective analysis in 160 patients.

PURPOSE: To assess indications, safety, and effectiveness of percutaneous adrenal mass biopsy in contemporary practice. METHODS: This institutional review board-approved, retrospective study included all patients undergoing percutaneous image-guided adrenal mass biopsies at an academic health system from January 6, 2015, to January 6, 2023. Patient demographics, biopsy indications, mass size, laboratory data, pathology results, and complications were recorded. Final diagnoses were based on pathology or ≥ 1 year of imaging follow-up when biopsy specimens did not yield malignant tissue. Test performance calculations excluded repeat biopsies. Continuous variables were compared with Student's t test, dichotomous variables with chi-squared test. RESULTS: A total of 160 patients underwent 186 biopsies. Biopsies were indicated to diagnose metastatic disease (139/186; 74.7%), for oncologic research only (27/186; 14.5%), diagnose metastatic disease and oncologic research (15/186; 8%), and diagnose an incidental adrenal mass (5/186; 2.7%). Biopsy specimens were diagnostic in 154 patients (96.3%) and non-diagnostic in 6 (3.8%). Diagnostic biopsies yielded malignant tissue (n = 136), benign adrenal tissue (n = 12), and benign adrenal neoplasms (n = 6) with sensitivity = 98.6% (136/138), specificity = 100% (16/16), positive predictive value = 100% (136/136), and negative predictive value = 88.9% (16/18). Adverse events followed 11/186 procedures (5.9%) and most minor (7/11, 63.6%). The adverse event rate was similar whether tissue was obtained for clinical or research purposes (10/144; 6.9% vs. 1/42; 2.4%, p = 0.27), despite more specimens obtained for research (5.8 vs. 3.7, p < 0.001). CONCLUSION: Percutaneous adrenal mass biopsy is safe, accurate, and utilized almost exclusively to diagnose metastatic disease or for oncologic research. The negative predictive value is high when diagnostic tissue samples are obtained. Obtaining specimens for research does not increase adverse event risk.