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RESEARCH QUESTION: Does a database of hospital admission data linked to police road traffic accident (RTA) reports produce less biased information for the injury prevention policymaker, planner, and practitioner than police RTA reports alone? DESIGN: Data linkage study. STUDY POPULATION: Non-fatal injury victims of road traffic crashes in southern England who were admitted to hospital. DATA SOURCES: Hospital admissions and police RTA reports. MAIN OUTCOME MEASURES: The estimated proportion of road traffic crashes admitted to hospital that were included on the linked database; distributions by age, sex, and road user groups: (A) for all RTA injury admissions and (B) for RTA serious injury admissions defined by length of stay or by nature of injury. RESULTS: An estimated 50% of RTA injury admissions were included on the linked database. When assessing bias, admissions data were regarded as the 'gold standard'. The distributions of casualties by age, sex, and type of road user showed major differences between the admissions data and the police RTA injury data of comparable severity. The linked data showed smaller differences when compared with admissions data. For RTA serious injury admissions, the distributions by age and sex were approximately the same for the linked data compared with admissions data, and there were small but statistically significant differences between the distributions across road user group for the linked data compared with hospital admissions. CONCLUSION: These results suggest that investigators could be misinformed if they base their analysis solely on police RTA data, and that information derived from the linked database is less biased than that from police RTA data alone. A national linked dataset of road traffic crash data should be produced from hospital admissions and police RTA data for use by policymakers, planners and practitioners. [ABSTRACT FROM AUTHOR]

In this review, we summarise the ongoing debate surrounding the anatomy of the atrioventricular conduction axis and its relevance to pacing. We highlight previous disagreements and emphasise the importance of understanding the anatomical location of the axis. We give credit and support to the initial descriptions by His and Tawara, in particular their attention to the relationship of the atrioventricular conduction axis with the membranous septum. We express our disagreements with recent diagrams that incorrectly, in our opinion, depict the left bundle and right bundle branches. We offer our own latest understanding of the location and relationships of the atrioventricular conduction axis, including details of its development, and differences between human and animal hearts. We also emphasise the importance of understanding the relationship between the inferior pyramidal space and the inferoseptal recess so as appropriately to place the axis within the heart. We conclude by emphasising the need to consider the heart in the context of the body, describing its component parts by using attitudinally appropriate nomenclature., Competing Interests: Disclosure: RHA is on the Arrhythmia & Electrophysiology Review editorial board; this did not affect peer review. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Background: Social constructs like race can affect how patients are perceived and impact care. This study investigated whether mentions of race in notes for critically ill patients differed according to patients' race., Methods: This retrospective cohort study included intensive care unit notes for adults (≥18 years old) admitted to any of 6 intensive care units at University of California, San Francisco, from 2012 through 2020. Notes were linked to National Provider Identifier records to obtain note writer characteristics. Logistic regression analysis with robust SEs clustered on note writers was adjusted for patient-, note- and clinician-level characteristics. Any race or ethnicity mention was the outcome of interest., Results: Among 5573 patients with 292 457 notes by 9742 unique note writers, 3225 patients (57.9%) self-reported their race as White, 997 (17.9%) as Asian, 860 (15.4%) as Latinx, and 491 (8.8%) as Black. Note writers documented race/ethnicity for 20.8% of Black, 10.9% of Latinx, 9.1% of White, and 4.4% of Asian patients. Black patients were more likely than White patients to have race mentioned in notes (adjusted odds ratio, 2.05 [95% CI, 1.49-2.82])., Conclusions: Black patients were more than twice as likely as White patients to have race mentioned in notes. Note language containing information on social constructs has consequences for clinicians and patients reading notes and for algorithms trained on clinical notes., (©2024 American Association of Critical-Care Nurses.)

Snap-frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three-dimensional (3D) structural information before multi-omics is more challenging but can potentially allow for better characterization of tissues and targeting of clinically relevant cells. Conventional histological techniques are limited in this regard due to their destructive nature and the reconstruction artifacts produced by sectioning, dehydration, and chemical processing. These limitations are particularly notable in soft tissues such as the heart. In this study, the feasibility of using synchrotron-based cryo-X-ray phase contrast imaging (cryo-X-PCI) of snap-frozen myocardial biopsies is assessed and 3D structure tensor analysis of aggregated myocytes, followed by nucleic acid (DNA and RNA) extraction and analysis. It is shown that optimal sample preparation is the key driver for successful structural and nucleic acid preservation which is unaffected by the process of cryo-X-PCI. It is proposed that cryo-X-PCI has clinical value for 3D tissue analysis of cardiac and potentially non-cardiac soft tissue biopsies before nucleic acid investigation., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Statistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective., Methods: Preliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification., Results: As expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset., Discussion: This study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lee, Martorana, Md, Sivera, Cook, Menezes, Burriesci, Torii and Bosi.)

Onychomycosis (OM) is a nail infection from various fungal species, representing a worldwide dermatologic health concern. The toenails are most often affected. Comorbid chronic health conditions and environmental and genetic factors play a role in the development of OM. It has been observed that certain populations have an increased risk of developing OM, suggesting an inherited component to its etiology. Recent studies have observed the impact of the human leukocyte antigen-DR (HLA-DR) profile on the likelihood of developing OM; however, none have aggregated these studies for a meta-analysis to determine a statistical effect. The literature was systematically reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to determine the effect of the HLA-DR profile on OM susceptibility. Studies that contained HLA-DR allele frequency data on patients with OM were included. Studies that contained too much allele frequency data, did not contain HLA-DR allele frequency data, or were written in a non-English language were excluded. Google Scholar, PubMed, and Scientific Direct databases were searched. The risk of bias was assessed by using the National Institutes of Health (NIH) quality assessment case-control study tool. The results were generated using Review Manager version 5.4 by extracting and inputting HLA-DR allele frequency data into the program. The program created aggregated odds ratios that were visually represented in forest plots. A total of five articles were included in the analysis. One hundred fifty-six patients with OM were used in this analysis. Mexican mestizos and United States Caucasian populations were represented in this study. Overall, the NIH risk of bias tool revealed that most studies included did not justify their sample size, or the assessors were not blinded. Of all the HLA-DR alleles analyzed, only HLA-DR8 revealed a statistically significant result with an odds ratio of 1.70 with a 95% CI (1.05-2.76). This suggests that HLA-DR8 confers a 70% higher risk of susceptibility to OM. This finding can help identify these target populations and serve as the basis for personalized treatment solutions., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cook et al.)

Context The osteopathic cranial field suggests that cranial rhythmic impulse (CRI) can be used to examine distal segments. However, there is a lack of research on the reliability of using CRI to diagnose other distal segments. This study aims to evaluate the effectiveness of using the cranial vault hold compared to traditional osteopathic diagnostic techniques to diagnose somatic dysfunctions at the following segments: atlantooccipital joint (OA), atlantoaxial joint (AA), cervical-4 (C4), cervical-7 (C7), thoracic-6 (T6), thoracic-12 (T12), lumbar-3 (L3), sacrum, left innominate, right fibular head, and left radial head. Objective To determine if palpation of CRI can reliably detect somatic dysfunctions in multiple distal segments. Methods The study compared osteopathic physicians' diagnoses of specific segments (OA, AA, C4, C7, T6, T12, L3, sacrum, left innominate, right fibular head, and left radial head) using the cranial vault hold and direct palpation. Two osteopathic neuromusculoskeletal medicine experts (cranial group) diagnosed distal segments via the cranial vault hold, while board-certified osteopathic physicians (confirmatory group) used direct palpation. We recruited 44 second-year osteopathic medical students and osteopathic physicians via a school-wide email. Each participant lay supine on a massage table for diagnosis. A neuromusculoskeletal expert, with a scribe, diagnosed the segments using the cranial vault hold. The process was repeated by a second neuromusculoskeletal expert with another scribe. Two osteopathic physicians then diagnosed the same subjects using direct palpatory techniques. Both osteopathic physicians had to agree on a diagnosis for the segment, or it was excluded from comparison. Cohen's kappa coefficient measured inter-rater reliability between the cranial and confirmatory groups. Results Cranial physician 1 provided all 484 diagnoses, while cranial physician 2 provided 152. Cranial physician 1 showed positive agreement with the confirmatory group (κ>0) in 2/11 (18.2%) segments: T12 and left innominate (κ=0.009 and 0.007). Cranial physician 2 showed positive agreement (κ>0) in 4/11 (36.4%) segments: OA, AA, C4, and left innominate (κ=0.050, 0.031, 0.130, and 0.154). Inter-rater reliability between cranial physicians showed positive agreement in 6/11 (54.5%) segments: OA, AA, C4, sacrum, left innominate, and right fibular head (κ=0.125, 0.022, 0.048, 0.036, 0.154, and 0.0261). Conclusion The positive kappa values, all between 0 and 0.2, indicate the inter-rater reliability for diagnosis with the vault hold is above random chance but has none to slight reliability. The kappa coefficients comparing both cranial physicians indicate positive agreement in six segments, supporting palpation of the same phenomena in six out of 11 (54.5%) segments. However, none of the positive kappa values were statistically significant (p>0.05) and the effect sizes were small, likely due to shared bias among the evaluators. We conclude our experiment suggests palpation of the cranium may not reliably diagnose distal segments. However, our experiment may support a connection between CRI and distal segment somatic dysfunctions. Considering diagnoses of certain segments are above random chance, more research is needed to confirm whether there is a connection between palpation of the CRI and the diagnosis of a distal somatic dysfunction., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Lake Erie College of Osteopathic Medicine issued approval 30-078. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alvarez et al.)

Objectives: Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined., Methods: Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA ( n = 80) and White participants ( n = 78)., Results: Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted)., Conclusions: Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

Despite centuries of investigation, certain aspects of left ventricular anatomy remain either controversial or uncertain. We make no claims to have resolved these issues, but our review, based on our current knowledge of development, hopefully identifies the issues requiring further investigation. When first formed, the left ventricle had only inlet and apical components. With the expansion of the atrioventricular canal, the developing ventricle cedes part of its inlet to the right ventricle whilst retaining the larger parts of the cushions dividing the atrioventricular canal. Further remodelling of the interventricular communication provides the ventricle with its outlet, with the aortic root being transferred to the left ventricle along with the newly formed myocardium supporting its leaflets. The definitive ventricle possesses inlet, apical and outlet parts. The inlet component is guarded by the mitral valve, with its leaflets, in the normal heart, supported by papillary muscles located infero-septally and supero-laterally. There is but a solitary zone of apposition between the leaflets, which we suggest are best described as being aortic and mural. The trabeculated component extends beyond the inlet to the apex and is confluent with the outlet part, which supports the aortic root. The leaflets of the aortic valve are supported in semilunar fashion within the root, with the ventricular cavity extending to the sinutubular junction. The myocardial-arterial junction, however, stops well short of the sinutubular junction, with myocardium found only at the bases of the sinuses, giving rise to the coronary arteries. We argue that the relationships between the various components should now be described using attitudinally appropriate terms rather than describing them as if the heart is removed from the body and positioned on its apex., (© 2024 Anatomical Society.)

Craniosacral treatment (CST) is an osteopathic technique grounded in the assumption that there is an intrinsic, fine movement of the cerebrospinal fluid. This rhythmic movement can be utilized for diagnostic and therapeutic purposes by palpation and manipulation of the skull, spine, and associated connective tissues. Therapeutic benefit is likely due to action on the autonomic nervous system (ANS), specifically through the vagus nerve. Current literature on the neurophysiological effects of CST is limited, which has contributed to controversy regarding its effectiveness. Heart rate variability (HRV) as a measure of cardiovascular stress and autonomic system activity is thus proposed as a tool to evaluate the neurophysiologic effects of CST. HRV can be analyzed in two different bands, high-frequency (HF) and low-frequency (LF) power associated with a parasympathetic and sympathetic response. In this meta-analysis, we provide a brief introduction to CST, analyze three primary studies, and summarize the therapeutic benefits and pitfalls of this alternative treatment on the ANS. A significant negative HF standardized mean difference after CST was observed; standardized mean difference = -0.46; 95% CI (-0.79,-0.14). No significant effect on LF power was observed. We conclude that CST does provide a moderate short-term increase in parasympathetic activity. These findings suggest that CST may be used to treat patients with an overactive sympathetic state. Further studies should be conducted for comparison against a control group to eliminate the possibility of a placebo effect and to elucidate long-term effects., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cook et al.)

Background Current clinical imaging modalities such as CT and MRI provide resolution adequate to diagnose cardiovascular diseases but cannot depict detailed structural features in the heart across length scales. Hierarchical phase-contrast tomography (HiP-CT) uses fourth-generation synchrotron sources with improved x-ray brilliance and high energies to provide micron-resolution imaging of intact adult organs with unprecedented detail. Purpose To evaluate the capability of HiP-CT to depict the macro- to microanatomy of structurally normal and abnormal adult human hearts ex vivo. Materials and Methods Between February 2021 and September 2023, two adult human donor hearts were obtained, fixed in formalin, and prepared using a mixture of crushed agar in a 70% ethanol solution. One heart was from a 63-year-old White male without known cardiac disease, and the other was from an 87-year-old White female with a history of multiple known cardiovascular pathologies including ischemic heart disease, hypertension, and atrial fibrillation. Nondestructive ex vivo imaging of these hearts without exogenous contrast agent was performed using HiP-CT at the European Synchrotron Radiation Facility. Results HiP-CT demonstrated the capacity for high-spatial-resolution, multiscale cardiac imaging ex vivo, revealing histologic-level detail of the myocardium, valves, coronary arteries, and cardiac conduction system across length scales. Virtual sectioning of the cardiac conduction system provided information on fatty infiltration, vascular supply, and pathways between the cardiac nodes and adjacent structures. HiP-CT achieved resolutions ranging from gross (isotropic voxels of approximately 20 µm) to microscopic (approximately 6.4-µm voxel size) to cellular (approximately 2.3-µm voxel size) in scale. The potential for quantitative assessment of features in health and disease was demonstrated. Conclusion HiP-CT provided high-spatial-resolution, three-dimensional images of structurally normal and diseased ex vivo adult human hearts. Whole-heart image volumes were obtained with isotropic voxels of approximately 20 µm, and local regions of interest were obtained with resolution down to 2.3-6.4 µm without the need for sectioning, destructive techniques, or exogenous contrast agents. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Bluemke and Pourmorteza in this issue.

Background: Language in nonmedical data sets is known to transmit human-like biases when used in natural language processing (NLP) algorithms that can reinforce disparities. It is unclear if NLP algorithms of medical notes could lead to similar transmissions of biases., Research Question: Can we identify implicit bias in clinical notes, and are biases stable across time and geography?, Study Design and Methods: To determine whether different racial and ethnic descriptors are similar contextually to stigmatizing language in ICU notes and whether these relationships are stable across time and geography, we identified notes on critically ill adults admitted to the University of California, San Francisco (UCSF), from 2012 through 2022 and to Beth Israel Deaconess Hospital (BIDMC) from 2001 through 2012. Because word meaning is derived largely from context, we trained unsupervised word-embedding algorithms to measure the similarity (cosine similarity) quantitatively of the context between a racial or ethnic descriptor (eg, African-American) and a stigmatizing target word (eg, nonco-operative) or group of words (violence, passivity, noncompliance, nonadherence)., Results: In UCSF notes, Black descriptors were less likely to be similar contextually to violent words compared with White descriptors. Contrastingly, in BIDMC notes, Black descriptors were more likely to be similar contextually to violent words compared with White descriptors. The UCSF data set also showed that Black descriptors were more similar contextually to passivity and noncompliance words compared with Latinx descriptors., Interpretation: Implicit bias is identifiable in ICU notes. Racial and ethnic group descriptors carry different contextual relationships to stigmatizing words, depending on when and where notes were written. Because NLP models seem able to transmit implicit bias from training data, use of NLP algorithms in clinical prediction could reinforce disparities. Active debiasing strategies may be necessary to achieve algorithmic fairness when using language models in clinical research., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Published by Elsevier Inc.)

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections.

X-ray phase contrast imaging (X-PCI) is a powerful technique for high-resolution, three-dimensional imaging of soft tissue samples in a non-destructive manner. In this technical report, we assess the quality of standard histopathological techniques performed on formalin-fixed, paraffin-embedded (FFPE) human tissue samples that have been irradiated with different doses of X-rays in the context of an X-PCI experiment. The data from this study demonstrate that routine histochemical and immunohistochemical staining quality as well as DNA and RNA analyses are not affected by previous X-PCI on human FFPE samples. From these data we conclude it is feasible and acceptable to perform X-PCI on FFPE human biopsies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The need to integrate palliative care (PC) training into surgical education has been increasingly recognized. Our aim is to describe a set of PC educational strategies, with a range of requisite resources, time, and prior expertise, to provide options that surgical educators can tailor for different programs. Each of these strategies has been successfully employed individually or in some combination at our institutions, and components can be generalized to other training programs. Asynchronous and individually paced PC training can be provided using existing resources published by the American College of Surgeons and upcoming SCORE curriculum modules. A multiyear PC curriculum, with didactic components of increasing complexity for more advanced residents, can be applied based on available time in the didactic schedule and local expertise. Simulation-based training in PC skills can be developed to provide objective competency-based training. Finally, a dedicated rotation on a surgical palliative care service can provide the most immersive experience with steps toward clinical entrustment of PC skills for trainees., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To develop proof-of-concept algorithms using alternative approaches to capture provider sentiment in ICU notes., Design: Retrospective observational cohort study., Setting: The Multiparameter Intelligent Monitoring of Intensive Care III (MIMIC-III) and the University of California, San Francisco (UCSF) deidentified notes databases., Patients: Adult (≥18 yr old) patients admitted to the ICU., Measurements and Main Results: We developed two sentiment models: 1) a keywords-based approach using a consensus-based clinical sentiment lexicon comprised of 72 positive and 103 negative phrases, including negations and 2) a Decoding-enhanced Bidirectional Encoder Representations from Transformers with disentangled attention-v3-based deep learning model (keywords-independent) trained on clinical sentiment labels. We applied the models to 198,944 notes across 52,997 ICU admissions in the MIMIC-III database. Analyses were replicated on an external sample of patients admitted to a UCSF ICU from 2018 to 2019. We also labeled sentiment in 1,493 note fragments and compared the predictive accuracy of our tools to three popular sentiment classifiers. Clinical sentiment terms were found in 99% of patient visits across 88% of notes. Our two sentiment tools were substantially more predictive (Spearman correlations of 0.62-0.84, p values < 0.00001) of labeled sentiment compared with general language algorithms (0.28-0.46)., Conclusion: Our exploratory healthcare-specific sentiment models can more accurately detect positivity and negativity in clinical notes compared with general sentiment tools not designed for clinical usage., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: To evaluate the impact of medical cannabis laws (MCLs) on health insurance premiums. We study whether cannabis legalization significantly impacts aggregate health insurer premiums in the individual market. Increases in utilization could have spillover effects to patients in the form of higher health insurance premiums., Methods: We use 2010-2021 state-level U.S. private health insurer financial data from the National Association of Insurance Commissioners. We examined changes to individual market health insurance premiums after the implementation of medical cannabis laws. We employed a robust difference-in-differences estimator that accounted for variation in policy timing to exploit temporal and geographic variation in state-level medical cannabis legalization., Results: Seven years after the implementation of Medical Cannabis laws, we observe lower health insurer premiums in the individual market. Starting seven years post-MCL implementation, we find a reduction of $-1662.7 (95% confidence interval [CI -2650.1, -605.7]) for states which implemented MCLs compared to the control group, a reduction of -$1541.8 (95% confidence interval [CI 2602.1, -481.4]) in year 8, and a reduction of $-1625.8, (95% confidence interval [CI -2694.2, -557.5]) in year 9. Due to the nature of insurance pooling and community rating, these savings are appreciated by cannabis users and non-users alike in states that have implemented MCLs., Conclusions: The implementation of MCLs lowers individual-market health insurance premiums. Health insurance spending, including premiums, comprises between 16% and 34% of household budgets in the United States. As healthcare costs continue to rise, our findings suggest that households that obtain their health insurance on the individual (i.e., not employer sponsored) market in states with MCLs appreciate significantly lower premiums., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To determine the impact of fraternity and sorority membership on condom use during sex. Methods: Utilizing data from The American College Health Association (ACHA) National College Health Assessment from 2016-2018, we estimated a linear probability, logistic, and instrumental variable model to determine the relationship between fraternity and sorority membership and the frequency of condom use during sex. Results: Compared to non-fraternity members, fraternity members experience an increase in sex without a condom for both oral sex (13.5%, 95% ci= 0.048, 0.221) and anal sex (28.5%, 95% ci= 0.174, 0.396). Compared to non-sorority members, sorority members are more likely to engage in oral sex without a condom. This result is not robust to single sorority members. Conclusions: Fraternity membership increases the probability of risky oral and anal sex. Policy Implications: The reduced use of condoms has implications on sexual health including an increased risk of contracting or spreading sexually transmitted infections.

The mammalian heart, which is one of the first organs to form and function during embryogenesis, develops from a simple tube into a complex organ able to efficiently pump blood towards the rest of the body. The progressive growth of the compact myocardium during embryonic development is accompanied by changes in its structural complexity and organisation. However, how myocardial myoarchitecture develops during embryogenesis remain poorly understood. To date, analysis of heart development has focused mainly on qualitative descriptions using selected 2D histological sections. High resolution episcopic microscopy (HREM) is a novel microscopic imaging technique that enables to obtain high-resolution three-dimensional images of the heart and perform detailed quantitative analyses of heart development. In this work, we performed a detailed characterization of the development of myocardial architecture in wildtype mice, from E14.5 to E18.5, by means of structure tensor analysis applied to HREM images of the heart. Our results shows that even at E14.5, myocytes are already aligned, showing a gradual change in their helical angle from positive angulation in the endocardium towards negative angulation in the epicardium. Moreover, there is gradual increase in the degree of myocardial organisation concomitant with myocardial growth. However, the development of the myoarchitecture is heterogeneous showing regional differences between ventricles, ventricular walls as well as between myocardial layers, with different growth patterning between the endocardium and epicardium. We also found that the percentage of circumferentially arranged myocytes within the LV significantly increases with gestational age. Finally, we found that fractional anisotropy (FA) within the LV gradually increases with gestational age, while the FA within RV remains unchanged., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcia-Canadilla, Mohun, Bijnens and Cook.)

Introduction: Dengue fever (DF) is a disease caused by dengue virus (DENV) from the family Flaviviridae. The role of human leukocyte antigens (HLAs) in dengue fever (DF) and its more severe manifestation, dengue hemorrhagic fever (DHF), has been a topic of great research interest. In addition to HLA profile, race, age, DENV serotype, infection while having certain chronic diseases, and secondary infection are risk factors for DHF susceptibility. Antibody-dependent enhancement (ADE) of dengue virus infection is a mechanism for DHF infection. Individual studies have examined the effects of HLA-A*24 and HLA-B*44 presence on DHF, but none have analyzed these in a meta-analysis. The objective of this study was to determine the effects of HLA-A*24 and HLA-B*44 presence on DHF and DF susceptibility., Materials and Methods: A meta-analysis on DHF and DF susceptibility in patients with HLA-A*24 and HLA-B*44 was conducted. Google Scholar was used to find studies that contained patients with HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF. Studies containing patients diagnosed using the 1997 WHO guidelines and possessing HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF, including primary or secondary infection, and studies measuring odds ratios (ORs) were included. Patients diagnosed using the 2009 WHO guidelines and studies in a foreign language, using animals, or lacking odds ratios were excluded. The National Institutes of Health (NIH) quality assessment of the case-control study tool was used, and a Doi plot was generated using MetaXL to assess for risk of bias. Review Manager version 5.4 was used to generate odds ratios and forest plots with subgroup analysis from allele and phenotype frequency data. Ten studies from 2001 to 2015 met the inclusion criteria. The studies included 2837 DHF/DF patients and 4880 healthy control (HC) patients., Results:  HLA-A*24 was associated with a 1.39 times susceptibility to DHF while those possessing HLA-B*44 were 0.62 times susceptible to DHF (OR=1.39 and 95% CI=1.17-1.66; OR=0.62 and 95% CI=0.39-0.99). Neither HLA-A*24 nor HLA-B*44 presence was associated with DF susceptibility (OR=1.04 and 95% CI=0.82-1.33; OR=0.88 and 95% CI=0.68-1.14)., Conclusion: These results indicate that two different major histocompatibility complex (MHC) class I alleles, HLA-A*24 and HLA-B*44, have opposing effects on DHF susceptibility but none on DF susceptibility. The study's specificity is limited in that it examines HLA allele groups and not specific HLA proteins. The results of this study can be used clinically to identify patients that may be at a higher risk of developing DHF based on their HLA profile., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Cook et al.)

The protein kinase PKN2 is required for embryonic development and PKN2 knockout mice die as a result of failure in the expansion of mesoderm, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The specific role of PKN2 in contractile cardiomyocytes during development and its role in the adult heart remain to be fully established. We used mice with cardiomyocyte-directed knockout of PKN2 or global PKN2 haploinsufficiency to assess cardiac development and function using high resolution episcopic microscopy, MRI, micro-CT and echocardiography. Biochemical and histological changes were also assessed. Cardiomyocyte-directed PKN2 knockout embryos displayed striking abnormalities in the compact myocardium, with frequent myocardial clefts and diverticula, ventricular septal defects and abnormal heart shape. The sub-Mendelian homozygous knockout survivors developed cardiac failure. RNASeq data showed up-regulation of PKN2 in patients with dilated cardiomyopathy, suggesting an involvement in adult heart disease. Given the rarity of homozygous survivors with cardiomyocyte-specific deletion of PKN2, the requirement for PKN2 in adult mice was explored using the constitutive heterozygous PKN2 knockout. Cardiac hypertrophy resulting from hypertension induced by angiotensin II was reduced in these haploinsufficient PKN2 mice relative to wild-type littermates, with suppression of cardiomyocyte hypertrophy and cardiac fibrosis. It is concluded that cardiomyocyte PKN2 is essential for heart development and the formation of compact myocardium and is also required for cardiac hypertrophy in hypertension. Thus, PKN signalling may offer therapeutic options for managing congenital and adult heart diseases., (© 2022 The Author(s).)

Context: Palliative care (PC) benefits critically ill patients but remains underutilized. Important to developing interventions to overcome barriers to PC in the ICU and address PC needs of ICU patients is to understand how, when, and for which patients PC is provided in the ICU., Objectives: Compare characteristics of specialty PC consultations in the ICU to those on medical-surgical wards., Methods: Retrospective analysis of national Palliative Care Quality Network data for hospitalized patients receiving specialty PC consultation January 1, 2013 to December 31, 2019 in ICU or medical-surgical setting. 98 inpatient PC teams in 16 states contributed data. Measures and outcomes included patient characteristics, consultation features, process metrics and patient outcomes. Mixed effects multivariable logistic regression was used to compare ICU and medical-surgical units., Results: Of 102,597 patients 63,082 were in medical-surgical units and 39,515 ICU. ICU patients were younger and more likely to have non-cancer diagnoses (all P < 0.001). While fewer ICU patients were able to report symptoms, most patients in both groups reported improved symptoms. ICU patients were more likely to have consultation requests for GOC, comfort care, and withdrawal of interventions and less likely for pain and/or symptoms (OR-all P < 0.001). ICU patients were less often discharged alive., Conclusion: ICU patients receiving PC consultation are more likely to have non-cancer diagnoses and less likely able to communicate. Although symptom management and GOC are standard parts of ICU care, specialty PC in the ICU is often engaged for these issues and results in improved symptoms, suggesting routine interventions and consultation targeting these needs could improve care., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The cardiac conduction system (CCS) comprises critical components responsible for the initiation, propagation, and coordination of the action potential. Aberrant CCS development can cause conduction abnormalities, including sick sinus syndrome, accessory pathways, and atrioventricular and bundle branch blocks. Gene Ontology (GO; http://geneontology.org/) is an invaluable global bioinformatics resource which provides structured, computable knowledge describing the functions of gene products. Many gene products are known to be involved in CCS development; however, this information is not comprehensively captured by GO. To address the needs of the heart development research community, this study aimed to describe the specific roles of proteins reported in the literature to be involved with CCS development and/or function. 14 proteins were prioritized for GO annotation which led to the curation of 15 peer-reviewed primary experimental articles using carefully selected GO terms. 152 descriptive GO annotations, including those describing sinoatrial node and atrioventricular node development were created and submitted to the GO Consortium database. A functional enrichment analysis of 35 key CCS development proteins confirmed that this work has improved the in-silico interpretation of this CCS dataset. This work may improve future investigations of the CCS with application of high-throughput methods such as genome-wide association studies analysis, proteomics, and transcriptomics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chloe Li, Cook and Lovering.)

Introduction: Although regular exercise is recommended during non-complicated pregnancies to promote maternal and fetal/infant health, estimates suggest that only 15% of expectant mothers achieve current exercise recommendations. Although lack of motivation and fear related to potential fetal injury are often cited as reasons for not engaging in regular physical activity/exercise during pregnancy, less is understood about individual attitudes and practice habits of obstetrician and gynecologists (OB/GYNs) regarding exercise recommendations that may influence patient engagement in exercise during pregnancy. Purpose: To describe the attitudes, knowledge, and clinical practice of OB/GYNs regarding exercise during pregnancy. Methods: Surveys were sent via U.S. mail to 950 practicing OB/GYNs identified via publicly available databases. The survey included 11 questions regarding demographic information, exercise physiology knowledge, as well as their attitudes and clinical practice recommendations regarding exercise during pregnancy. Results: One hundred thirty-nine completed surveys were returned (14.6% response rate). Ninety-four percent of physicians surveyed agreed that there are benefits of exercise during pregnancy and/or the benefits of exercise during pregnancy outweigh the risks. Ninety-eight percent of physicians surveyed reported that they (or their medical staff) routinely advise their patients to exercise during pregnancy and 46% reported discussing exercise guidelines related to time, intensity, and type of exercise. Only 13% of physicians surveyed reported taking a semester-long exercise physiology course, yet 27% of physicians surveyed reported developing personalized exercise prescriptions for all (6%) or some (21%) of their patients. Conclusions: Low exercise engagement among expectant mothers does not appear to be due to a lack of guidance or negative views of OB/GYNs regarding exercise during pregnancy., Competing Interests: The authors have no conflicts of interest to report., (© Rachael K. Nelson et al., 2022; Published by Mary Ann Liebert, Inc.)

Context: Critically ill patients have important palliative care (PC) needs in the intensive care unit (ICU), but specialty PC is often underutilized., Objective: To evaluate changes in utilization and reasons for PC consultation over time., Methods: Data from a national multi-site network of inpatient PC visits were used to identify patients age ≥18 years admitted to an ICU between 2013 and 2019. Year of ICU admission was the exposure. Primary diagnosis and reason for referral were identified by standardized process measures within the dataset at the time of referral. Trends in primary diagnosis and reason for referral were modeled as a function of year of ICU admission., Results: Across 39,515 ICU patients seen by a PC team, overall numbers of consultations from the ICU increased each year. Referrals for patients with cancer decreased from 17.6% (95% CI 13.7%-21.5%) to 14.3% (95% CI 13.2%-14.7%) and for patients with cardiovascular disease increased from 16.8% in (95% CI 16.8%-16.9%) to 18.8% (95% CI 18.8%-18.9%). Reasons for referrals were primarily for goals of care and advance care planning and increased from 74.0% (95% CI 70.0%-78.0%) in 2013 to 80.0% (95% CI 79.4%-80.0%) in 2019 (P < 0.0001 for all trends)., Conclusion: PC referrals in ICU patients with cancer are decreasing, while those for cardiovascular disease are increasing. Reasons for referrals in the ICU are commonly for goals of care; other reasons, like pain control are uncommon. Early goals of care conversations and further training in advance care planning should be emphasized in the ICU setting., (Published by Elsevier Inc.)

Background: Serious illness communication skills are important tools for surgeons, but training in residency is limited., Methods: Thirteen senior surgical residents at an academic center were interviewed about their experiences with serious illness communication. Conventional content analysis was performed using established communication frameworks and inductive development of themes., Results: Residents had frequent conversations and employed known communication strategies. Three themes highlighted challenges they face. Illness severity included factors attributed to the illness that made serious illness communication more challenging: symptoms, poor prognosis, and urgency. Knowledge and feelings included the factual understanding and emotional experience of residents, patients, and families. Academic structure included hierarchy and the residents' dual role as learners and teachers. On reflection, residents identified needing greater experiential practice, analogous to learning procedural skills., Conclusions: Surgical residents regularly face serious illness conversations with little training beyond observation of role models. Dedicated training may help meet this need., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We aim to determine any additional benefit of virtual reality (VR) experience if compared to conventional cross-sectional imaging and standard three-dimensional (3D) modelling when deciding on surgical strategy in patients with complex double outlet right ventricle (DORV)., Methods and Results: We retrospectively selected 10 consecutive patients with DORV and complex interventricular communications, who underwent biventricular repair. An arterial switch operation (ASO) was part of the repair in three of those. Computed tomography (CT) or cardiac magnetic resonance imaging images were used to reconstruct patient-specific 3D anatomies, which were then presented using different visualization modalities: 3D pdf, 3D printed models, and VR models. Two experienced paediatric cardiac surgeons, blinded to repair performed, reviewed each case evaluating the suitability of repair following assessment of each visualization modalities. In addition, they had to identify those who had ASO as part of the procedure. Answers of the two surgeons were compared to the actual operations performed. There was no mortality during the follow-up (mean = 2.5 years). Two patients required reoperations. After review of CT/cardiac magnetic resonance images, the evaluators identified the surgical strategy in accordance with the actual surgical plan in 75% of the cases. When using 3D pdf this reached only 70%. Accordance improved to 85% after revision of 3D printed models and to 95% after VR. Use of 3D printed models and VR facilitated the identification of patients who required ASO., Conclusion: Virtual reality can enhance understanding of suitability for biventricular repair in patients with complex DORV if compared to cross-sectional images and other 3D modelling techniques., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Signaling from an actively remodeling extracellular matrix (ECM) has emerged as a critical factor in regulating both the repair of tissue injuries and the progression of diseases such as metastatic cancer. Hyaluronan (HA) is a major component of the ECM that normally functions in tissue injury to sequentially promote then suppress inflammation and fibrosis, a duality in which is featured, and regulated in, wound repair. These essential response-to-injury functions of HA in the microenvironment are hijacked by tumor cells for invasion and avoidance of immune detection. In this review, we first discuss the numerous size-dependent functions of HA and emphasize the multifunctional nature of two of its receptors (CD44 and RHAMM) in regulating the signaling duality of HA in excisional wound healing. This is followed by a discussion of how HA metabolism is de-regulated in malignant progression and how targeting HA might be used to better manage breast cancer progression.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code ( IPCCC ) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC . The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD) , in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature . This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC , as IPCCC continues to evolve.

There is growing interest in, and need for, integrating palliative care (PC) into the care of patients undergoing emergency surgery and those with traumatic injury. Thus, PC consults for these populations will likely grow in the coming years. Understanding the nuances and unique characteristics of these two acutely ill populations will improve the care that PC clinicians can provide. Using a modified Delphi technique, this article offers 10 tips that experts in the field, based on their broad clinical experience, believe PC clinicians should know about the care of trauma and emergency surgery patients.

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm.

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Seriously ill surgical patients require complex and integrated surgical, interventional, and medical management to balance the risks and benefits that complicate decision-making. Palliative care principles can aid surgeons in these cases. To illustrate this, we describe a scenario of a patient with unresectable hepatocellular carcinoma with portal vein tumor thrombus causing portal hypertension. We discuss options for managing the sequelae of portal hypertension, including varices and ascites. We explore the interventional and surgical options for mitigating or palliating the underlying portal hypertension. Advances in interventional radiological techniques can facilitate the creation of transjugular intrahepatic portosystemic shunts (TIPSs), even with extensive portal vein thrombus. If interventional approaches are not possible, surgical shunts can be considered but carry significant risks that must be weighed against the benefits. To communicate effectively, we outline key steps to breaking bad news. To make shared decisions in challenging cases, we describe how to elicit a patient's hopes, expectations, concerns, and preferences; how to synthesize goals of care from these stated values; and how to use those goals to guide decision-making.

The heart is a complex multi-scale system composed of components integrated at the subcellular, cellular, tissue and organ levels. The myocytes, the contractile elements of the heart, form a complex three-dimensional (3D) network which enables propagation of the electrical signal that triggers the contraction to efficiently pump blood towards the whole body. Cardiovascular diseases (CVDs), a major cause of mortality in developed countries, often lead to cardiovascular remodeling affecting cardiac structure and function at all scales, from myocytes and their surrounding collagen matrix to the 3D organization of the whole heart. As yet, there is no consensus as to how the myocytes are arranged and packed within their connective tissue matrix, nor how best to image them at multiple scales. Cardiovascular imaging is routinely used to investigate cardiac structure and function as well as for the evaluation of cardiac remodeling in CVDs. For a complete understanding of the relationship between structural remodeling and cardiac dysfunction in CVDs, multi-scale imaging approaches are necessary to achieve a detailed description of ventricular architecture along with cardiac function. In this context, ventricular architecture has been extensively studied using a wide variety of imaging techniques: ultrasound (US), optical coherence tomography (OCT), microscopy (confocal, episcopic, light sheet, polarized light), magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and, more recently, synchrotron X-ray phase contrast imaging (SR X-PCI). Each of these techniques have their own set of strengths and weaknesses, relating to sample size, preparation, resolution, 2D/3D capabilities, use of contrast agents and possibility of performing together with in vivo studies. Therefore, the combination of different imaging techniques to investigate the same sample, thus taking advantage of the strengths of each method, could help us to extract the maximum information about ventricular architecture and function. In this review, we provide an overview of available and emerging cardiovascular imaging techniques for assessing myocardial architecture ex vivo and discuss their utility in being able to quantify cardiac remodeling, in CVDs, from myocyte to whole organ., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-269). The series “Right Ventricular Dysfunction” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Caregiver burden (CB) in Parkinson's disease (PD) does not improve in the short term after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), despite motor improvement. This may be due to increased caregiver demands after surgery or the possibility that DBS unresponsive non-motor factors, such as executive dysfunction, contribute to CB., Objective: To evaluate the trajectory of CB in year 2 following bilateral STN DBS surgery for PD, and to test whether post-operative CB changes correlate with changes in executive function in a subgroup with available neuropsychological testing., Methods: This retrospective analysis included 35 patients with PD whose caregivers completed the Caregiver Burden Inventory (CBI) at baseline and between 9 and 24 months after bilateral STN DBS. 14 of these patients had neuropsychological testing both at baseline and within 6 months of their follow up CBI assessment., Results: CBI scores showed worsened CB from baseline to follow-up (16.4-21.5, p = 0.006). There was no correlation between change in executive function and change in CBI in the smaller subsample., Conclusion: CB worsens in the 2 years after bilateral STN DBS despite improvement in motor symptoms and is not associated with change in executive dysfunction in the setting of advancing PD. These findings have implications on pre-operative counselling for patients and caregivers considering DBS for PD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted response to treatment. Decision analysis and techniques of reinforcement learning theoretically can mitigate these challenges but are poorly understood and rarely used clinically. This review seeks to promote an understanding of decision analysis and reinforcement learning by describing their use in the context of surgical decision-making., Methods: Cochrane, EMBASE, and PubMed databases were searched from their inception to June 2019. Included were 41 articles about cognitive and diagnostic errors, decision-making, decision analysis, and machine-learning. The articles were assimilated into relevant categories according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines., Results: Requirements for time-consuming manual data entry and crude representations of individual patients and clinical context compromise many traditional decision-support tools. Decision analysis methods for calculating probability thresholds can inform population-based recommendations that jointly consider risks, benefits, costs, and patient values but lack precision for individual patient-centered decisions. Reinforcement learning, a machine-learning method that mimics human learning, can use a large set of patient-specific input data to identify actions yielding the greatest probability of achieving a goal. This methodology follows a sequence of events with uncertain conditions, offering potential advantages for personalized, patient-centered decision-making. Clinical application would require secure integration of multiple data sources and attention to ethical considerations regarding liability for errors and individual patient preferences., Conclusion: Traditional decision-support tools are ill-equipped to accommodate time constraints and uncertainty regarding diagnoses and the predicted response to treatment, both of which often impair surgical decision-making. Decision analysis and reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess the feasibility of retrieval of intact human fetal hearts after first trimester surgical termination of pregnancy (TOP) and subsequent anatomical assessment by postmortem micro-computed tomography (micro-CT)., Methods: In a cohort of consenting women undergoing surgical TOP between 8 and 13 weeks' gestation, we attempted the retrieval of the fetal heart from the suction material. Specimens were immersion fixed in 10% formaldehyde, scanned by iodine-enhanced micro-CT and cardiac anatomy assessed by a multidisciplinary team using 3D-multiplanar analysis., Results: The median gestational age at TOP was 10.7 weeks (range 8.3-12.9). In 57 (95.0%) out of 60 suction specimens, the heart could be retrieved. The median cardiac length was 5 mm (range 2-8 mm), in three (5.3%), the heart was too damaged to assess cardiac anatomy and in five (8.7%) only the four chambers could be examined. In the remaining 49 (86.0%) cases, a detailed assessment of cardiac anatomy was possible, showing a major defect in two (4.1%) and a minor defect in four (8.2%)., Conclusions: Fetal hearts can be retrieved after first trimester TOP being intact in the vast majority of cases. Iodine-enhanced, postmortem micro-CT can be used to assess cardiac anatomy from as early as 8 weeks and to describe heart abnormalities., (© 2020 John Wiley & Sons, Ltd.)