Evaluation of an artificial intelligence-based decision support for detection of cutaneous melanoma in primary care - a prospective, real-life, clinical trial.

BACKGROUND: Use of artificial intelligence, or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has in several retrospective studies shown high levels of diagnostic accuracy on par with, or even outperforming, experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary health care setting by primary care physicians; with or without access to teledermoscopic support from dermatology clinics. OBJECTIVE: To determine the diagnostic performance of an artificial intelligence-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion. METHODS: This prospective, multicentre, clinical trial was conducted at 36 primary care centres in Sweden. The physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedure, by surgical excision or referral to dermatologist. After completed investigation, lesion diagnoses were collected from the patients' medical records and compared to app outcome and other lesion data. RESULTS: In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy (95% confidence interval) in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 (0.928-0.980), corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively. CONCLUSIONS: The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively on primary care patients, which could add significant clinical value for primary care physicians in assessing skin lesions to detect melanoma. ClinicalTrials.gov Identifier: NCT05172232.

Intrarater and Interrater Reliability of Radiographic Characteristics in Skeletally Immature Patients With Anterior Cruciate Ligament Tears: A PLUTO Study Group Reliability Study.

BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears. STUDY DESIGN: Cohort study (diagnosis). METHODS: Three fellowship-trained orthopaedic surgeons and 1 medical student performed 2 rounds of radiographic measurements on digital imaging (lateral knee radiographs and long-leg radiographs) of skeletally immature patients with ACL tears. Intrarater and interrater reliability for continuous radiographic measurements was assessed with intraclass correlation coefficients (ICCs) across 4 raters with 95% CIs for affected and unaffected side measurements. Interrater reliability analysis used an ICC (2, 4) structure and intrarater reliability analysis used an ICC (2, 1) structure. A weighted kappa coefficient was calculated for ordinal variables along with 95% CIs for both interrater and intrarater reliability. Agreement statistic interpretations are based on scales described by Fleiss, and Cicchetti and Sparrow: <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; and >0.74, excellent. RESULTS: Radiographs from a convenience sample of 43 patients were included. Intrarater reliability was excellent for nearly all measurements and raters. Interrater reliability was also excellent for nearly all reads for all measurements. CONCLUSION: Radiographic reliability of long-leg radiographs and lateral knee x-rays in skeletally immature children with ACL tears is excellent across nearly all measures and raters and can be obtained and interpreted as reliable and reproducible means to measure limb length and alignment. LEVEL OF EVIDENCE: Level III.

Are People Generous When the Financial Stakes Are High?

How generous are people when making consequential financial decisions in the real world? We took advantage of a rare opportunity to examine generosity among a diverse sample of adults who received a gift of U.S. $10,000 from a pair of wealthy donors, with nearly no strings attached. Two-hundred participants were drawn from three low-income countries (Indonesia, Brazil, and Kenya) and four high-income countries (Australia, Canada, the United Kingdom, and the United States) as part of a preregistered study. On average, participants spent over $6,400 on purchases that benefited others, including nearly $1,700 on donations to charity, suggesting that humans exhibit remarkable generosity even when the stakes are high. To address whether generosity was driven by reputational concerns, we asked half the participants to share their spending decisions publicly on Twitter, whereas the other half were asked to keep their spending private. Generous spending was similar between the groups, in contrast to our preregistered hypothesis that enhancing reputational concerns would increase generosity.

Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma.

Group 3 medulloblastoma (G3 MB) carries the worst prognosis of all MB subgroups. MYC oncoprotein is elevated in G3 MB tumors; however, the mechanisms that support MYC abundance remain unclear. Using metabolic and mechanistic profiling, we pinpoint a role for mitochondrial metabolism in regulating MYC. Complex-I inhibition decreases MYC abundance in G3 MB, attenuates the expression of MYC-downstream targets, induces differentiation, and prolongs male animal survival. Mechanistically, complex-I inhibition increases inactivating acetylation of antioxidant enzyme SOD2 at K68 and K122, triggering the accumulation of mitochondrial reactive oxygen species that promotes MYC oxidation and degradation in a mitochondrial pyruvate carrier (MPC)-dependent manner. MPC inhibition blocks the acetylation of SOD2 and oxidation of MYC, restoring MYC abundance and self-renewal capacity in G3 MB cells following complex-I inhibition. Identification of this MPC-SOD2 signaling axis reveals a role for metabolism in regulating MYC protein abundance that has clinical implications for treating G3 MB.

Establishment and Utility of SwedAD: A Nationwide Swedish Registry for Patients with Atopic Dermatitis Receiving Systemic Pharmacotherapy.

SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

Transseptal puncture during catheter ablation associated with higher radiation exposure.

BACKGROUND: Electroanatomic mapping systems are increasingly used during ablations to decrease the need for fluoroscopy and therefore radiation exposure. For left-sided arrhythmias, transseptal puncture is a common procedure performed to gain access to the left side of the heart. We aimed to demonstrate the radiation exposure associated with transseptal puncture. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry. Patients with left-sided accessory pathway-mediated tachycardia, with a structurally normal heart, who had a transseptal puncture, and were under 22 years of age were included. Those with previous ablations, concurrent diagnostic or interventional catheterisation, and missing data for fluoroscopy use or procedural outcomes were excluded. Patients with a patent foramen ovale who did not have a transseptal puncture were selected as the control group using the same criteria. Procedural outcomes were compared between the two groups. RESULTS: There were 284 patients in the transseptal puncture group and 70 in the patent foramen ovale group. The transseptal puncture group had a significantly higher mean procedure time (158.8 versus 131.4 minutes, p = 0.002), rate of fluoroscopy use (38% versus 7%, p < 0.001), and mean fluoroscopy time (2.4 versus 0.6 minutes, p < 0.001). The acute success and complication rates were similar. CONCLUSIONS: Performing transseptal puncture remains a common reason to utilise fluoroscopy in the era of non-fluoroscopic ablation. Better tools are needed to make non-fluoroscopic transseptal puncture more feasible.

Treatment Patterns among Patients with Atopic Dermatitis in Secondary Care: A National, Observational, Non-interventional, Retrospective Study in Sweden.

This non-interventional, observational, longitudinal study describes treatment patterns of atopic dermatitis (AD) in Sweden. Data from 3 Swedish registries were merged, and included patients who received an AD diagnosis (during the period 1997 to 2019) and had AD treatment prescribed (during the period 2006 to 2020). Treatment persistence, treatment sequencing, time-to-event analysis, and 12-month prevalence were analysed. Overall, data for 99,885 patients with AD were included, of whom 4,086 (4.1%) received systemic treatments. Median persistence rates were 12.6 (95% CI 11.9, 13.4) months for methotrexate, 10.8 (9.1, 13.0) months for azathioprine, 5.6 (3.8, 6.2) months for mycophenolate, 5.1 (4.4, 5.7) months for alitretinoin and 3.4 (3.2, 3.7) months for cyclosporine. Median (Q1, Q3) time from first secondary care visit for AD to first systemic treatment was 5.8 (2.2, 11.0) years overall and 4.4 (1.3, 9.1) years in the Stockholm region. Methotrexate was a prominent first- and second-line treatment used during the period 2006 to 2020. Dupilumab was introduced during the study period and was increasingly used as first- or second-line therapy over time. The 12-month prevalence of AD generally remained steady, with a gradual increase observed over time for the overall population. A steep increase was observed in Stockholm from 2011. This study shows that a small proportion of patients with AD are offered systemic treatments in Sweden, with long periods in secondary care prior to systemic treatments and low persistence on systemic treatments. Regional differences highlight a need for national treatment guidelines.

Targeting Triple-Negative Breast Cancer by a Novel Proteolysis Targeting Chimera Degrader of Enhancer of Zeste Homolog 2.

Enhancer of zeste homolog 2 (EZH2), a catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed in triple-negative breast cancer (TNBC), correlating with poor prognosis. However, EZH2 catalytic inhibitors are ineffective in suppressing the growth of TNBC cells that are dependent on EZH2. Knockdown of EZH2 inhibits the proliferation of these cells, suggesting that EZH2 protein overexpression but not its catalytic activity is critical for driving TNBC progression. Several proteolysis targeting chimera (PROTAC) degraders of EZH2, including the von Hippel-Lindau (VHL)-recruiting PROTAC YM281, have been reported. However, the effects of these EZH2 PROTACs in TNBC cells were not investigated. Here, we report the discovery and characterization of a novel, potent, and selective EZH2 PROTAC degrader, MS8815 (compound 16), which induced robust EZH2 degradation in a concentration-, time-, and proteasome-dependent manner in TNBC cells. Importantly, 16 effectively suppressed the cell growth in multiple TNBC cell lines and primary patient TNBC cells.

Quality improvement in juvenile idiopathic arthritis: a mixed-methods implementation pilot of the CAPTURE-JIA dataset.

BACKGROUND: A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes. This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data. METHODS: A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool. RESULTS: Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families. Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system. CONCLUSIONS: Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.

Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches.

The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69−84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.

Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers.

Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm2. Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0-2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers-An Explorative In Vivo Study.

The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

Water and hemoglobin modulated gelatin-based phantoms to spectrally mimic inflamed tissue in the validation of biomedical techniques and the modeling of microdialysis data.

SIGNIFICANCE: Tissue simulating phantoms are an important part of validating biomedical optical techniques. Tissue pathology in inflammation and oedema involves changes in both water and hemoglobin fractions. AIM: We present a method to create solid gelatin-based phantoms mimicking inflammation and oedema with adjustable water and hemoglobin fractions. APPROACH: One store-bought gelatin and one research grade gelatin were evaluated. Different water fractions were obtained by varying the water-to-gelatin ratio. Ferrous stabilized human hemoglobin or whole human blood was added as absorbers, and the stability and characteristics of each were compared. Intralipid® was used as the scatterer. All phantoms were characterized using spatial frequency domain spectroscopy. RESULTS: The estimated water fraction varied linearly with expected values (R2 = 0.96 for the store-bought gelatin and R2 = 0.99 for the research grade gelatin). Phantoms including ferrous stabilized hemoglobin stayed stable up to one day but had methemoglobin present at day 0. The phantoms with whole blood remained stable up to 3 days using the store-bought gelatin. CONCLUSIONS: A range of physiological relevant water fractions was obtained for both gelatin types, with the stability of the phantoms including hemoglobin differing between the gelatin type and hemoglobin preparation. These low-cost phantoms can incorporate other water-based chromophores and be fabricated as thin sheets to form multilayered structures.

Robotic Assistance for Posterior Approach Total Hip Arthroplasty Is Associated With Lower Risk of Revision for Dislocation When Compared to Manual Techniques.

BACKGROUND: Robotic-assistance total hip arthroplasty (RA-THA) and computer navigation THA (CN-THA) have been shown to improve accuracy of component positioning compared to manual techniques; however, controversy exists regarding clinical benefit. Moreover, these technologies may expose patients to risks. The purpose of this study is to compare rates of intraoperative fracture and complications requiring reoperation within 1 year for posterior approach RA-THA, CN-THA, and THA with no technology (Manual-THA). METHODS: In total, 13,802 primary, unilateral, elective, posterior approach THAs (1770 RA-THAs, 3155 CN-THAs, and 8877 Manual-THAs) were performed at a single institution between 2016 and 2020. Intraoperative fractures and reoperations within 1 year of the index procedure were identified. Cohorts were balanced using inverse probability of treatment weight based on age, gender, body mass index, femoral cementation, history of spine fusion, and Charlson Comorbidity Index. Logistic regression was performed to create odds ratios for complications. Additional regression analysis for dislocation was performed, adjusting for dual mobility and femoral head size. RESULTS: There were no differences in intraoperative fracture and postoperative complication rates between the groups (P = .521). RA-THA had a 0.3 odds ratio (95% confidence interval 0.1-0.9, P = .046) compared to Manual-THA for reoperation due to dislocation. CN-THA had an odds ratio of 3.0 for reoperation due to dislocation (95% confidence interval 0.8-11.3, P = .114) compared to RA-THA. The remaining complication odds ratios, including those for infection, loosening, dehiscence, and "other" were similar between the groups. CONCLUSION: RA-THA is associated with lower risk of revision for dislocation within 1 year of index surgery, when compared to Manual-THA performed through the posterior approach.

Treatment Patterns and Clinical Outcomes of Chronic Urticaria: Two-year Follow-up Results from the Scandinavian AWARE Study.

The AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) study investigated outcomes in patients with chronic urticaria refractory to H1-antihistamine. The objective of the current study was to analyse the effects of treatment on patients' symptoms and quality of life for a period of up to 2 years. Over the 2 years, there was clear improvement in the high rates of disease burden from baseline, as evidenced by lower scores for disease severity scales, better quality of life, and a decreasing rate of medical resource utilization. However, this is the result of treatment adherence to the guidelines in highly specialized Scandinavian urticaria centres, and has its basis in the relatively low treatment intensity and control at enrolment. There is a need for greater adherence to the treatment guidelines and better management of antihistamine-refractory chronic urticaria.

Micropuncture closure following high density microarray patch application in healthy subjects.

BACKGROUND: The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. MATERIALS AND METHODS: 1 × 1 cm HD-MAP patches containing 5000, 250-µm long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. RESULTS: Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. CONCLUSIONS: Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this paper's demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Radium in New Zealand agricultural soils: Crop uptake and estimation of current and future ionising radiation dose.

Crop uptake of 226Ra over a range of key New Zealand agricultural and horticultural growing areas was analysed to establish the dietary implications of an increase in soil 226Ra activity concentrations. Thirty crop samples, covering both feed and food commodities, were quantified for 226Ra activity concentrations, and concentration ratio (CRs) from the soil activity were calculated. The calculated CRs correlated with international default values for estimating crop uptake. Variation in CRs established that there was no increase in the crop activity concentration, relative to soil 226Ra from pasture foliage at a fertiliser impacted site, with a gradient of soil 226Ra activity concentrations. Based on the calculated CRs, the upper bound of the theoretical range of dietary exposures to 226Ra was 78.1 µSv/yr for teenage boys. Future forecasting of the increased dietary dose of 226Ra that might occur at the current soil loading rate, based on current fertiliser activity concentrations, confirmed that long-term loading of soil with 226Ra is unlikely to present a dietary risk. The forecast model calculated that the increase in dietary ionising radiation burden is unlikely to reach thresholds requiring regulatory intervention for two millennia.

Why is it so difficult to study magnetic compass orientation in murine rodents?

A magnetic compass sense has been demonstrated in all major classes of vertebrates, as well as in many invertebrates. In mammals, controlled laboratory studies of mice have provided evidence for a robust magnetic compass that is comparable to, or exceeds, the performance of that in other animals. Nevertheless, the vast majority of laboratory studies of spatial behavior and cognition in murine rodents have failed to produce evidence of sensitivity to magnetic cues. Given the central role that a magnetic compass sense plays in the spatial ecology and cognition of non-mammalian vertebrates, and the potential utility that a global/universal reference frame derived from the magnetic field would have in mammals, the question of why responses to magnetic cues have been so difficult to demonstrate reliably is of considerable importance. In this paper, we review evidence that the magnetic compass of murine rodents shares a number of properties with light-dependent compasses in a wide variety of other animals generally believed to be mediated by a radical pair mechanism (RPM) or related quantum process. Consistent with the RPM, we summarize both published and previously unpublished findings suggesting that the murine rodent compass is sensitive to low-level radio frequency (RF) fields. Finally, we argue that the presence of anthropogenic RF fields in laboratory settings, may be an important source of variability in responses of murine rodents to magnetic cues.

Utilising electroanatomic mapping during ablation in patients with CHD to reduce radiation exposure.

BACKGROUND: Patients with CHD can be exposed to high levels of cumulative ionising radiation. Utilisation of electroanatomic mapping during catheter ablation leads to reduced radiation exposure in the general population but has not been well studied in patients with CHD. This study evaluated the radiation sparing benefit of using three-dimensional mapping in patients with CHD. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy multi-institutional registry. Patients with CHD were selected. Those with previous ablations, concurrent diagnostic or interventional catheterisation and unknown arrhythmogenic foci were excluded. The control cohort was matched for operating physician, arrhythmia mechanism, arrhythmia location, weight and age. The procedure time, rate of fluoroscopy use, fluoroscopy time, procedural success, complications, and distribution of procedures per year were compared between the two groups. RESULTS: Fifty-six patients with congenital heart disease and 56 matched patients without CHD were included. The mean total procedure time was significantly higher in patients with CHD (212.6 versus 169.5 minutes, p = 0.003). Their median total fluoroscopy time was 4.4 minutes (compared to 1.8 minutes), and their rate of fluoroscopy use was 23% (compared to 13%). The acute success and minor complication rates were similar and no major complications occurred. CONCLUSIONS: With the use of electroanatomic mapping during catheter ablation, fluoroscopy use can be reduced in patients with CHD. The majority of patients with CHD received zero fluoroscopy.

Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury.

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the "one-treatment fits all" approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex "-omics" data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.