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Introduction: Breath Volatile organic compounds (VOCs) are promising biomarkers for clinical purposes due to their unique properties. Translation of VOC biomarkers into the clinic depends on identification and validation: a challenge requiring collaboration, well-established protocols, and cross-comparison of data. Previously, we developed a breath collection and analysis method, resulting in 148 breath-borne VOCs identified., Objectives: To develop a complementary analytical method for the detection and identification of additional VOCs from breath. To develop and implement upgrades to the methodology for identifying features determined to be "on-breath" by comparing breath samples against paired background samples applying three metrics: standard deviation, paired t-test, and receiver-operating-characteristic (ROC) curve., Methods: A thermal desorption (TD)-gas chromatography (GC)-mass spectrometry (MS)-based analytical method utilizing a PEG phase GC column was developed for the detection of biologically relevant VOCs. The multi-step VOC identification methodology was upgraded through several developments: candidate VOC grouping schema, ion abundance correlation based spectral library creation approach, hybrid alkane-FAMES retention indexing, relative retention time matching, along with additional quality checks. In combination, these updates enable highly accurate identification of breath-borne VOCs, both on spectral and retention axes., Results: A total of 621 features were statistically determined as on-breath by at least one metric (standard deviation, paired t-test, or ROC). A total of 38 on-breath VOCs were able to be confidently identified from comparison to chemical standards., Conclusion: The total confirmed on-breath VOCs is now 186. We present an updated methodology for high-confidence VOC identification, and a new set of VOCs commonly found on-breath., Competing Interests: Declarations. Competing interests: BB is the CEO and Co-Founder of Owlstone Medical Ltd. WA, HC, JG, MB, OB, SC, PG, AR, EL, MT, MS, SL, EM, CCP, LND, SS, and MA are, or were employees of Owlstone Medical Ltd at the time this work was completed. Ethical approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study, in accordance with ICH GCP. The study supporting this work was approved by the Reading Independent Ethics Committee RIEC: 290620-1., (© 2025. The Author(s).)

Background: The neurobiological basis of impulsivity and its role in suicide attempt (SA) in BD remains underexplored. This study aimed to examine the functional connectivity (FC) within the prefrontal cortex (PFC) in BD patients with and without a history of SA, focusing on the role of trait impulsivity., Methods: Seventy-two euthymic BD patients (34 with a history of SA, BDSA; and 38 without, BDNS) and 55 age- and sex-matched healthy controls underwent resting-state functional MRI. FC analyses were conducted on four PFC regions: superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC). Trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), and its association with FC was analyzed using a general linear model, adjusting for demographic and clinical variables., Results: BDSA had higher trait impulsivity than BDNS and the controls. BDSA exhibited reduced FC between the PFC and sensorimotor (postcentral and precentral gyri) and thalamic regions compared to BDNS. These reductions in FC of the fronto-thalamic and fronto-sensorimotor circuits were significantly associated with higher trait impulsivity scores., Conclusion: The findings highlight specific PFC-based FC alterations associated with suicide attempts and trait impulsivity in BD, offering potential neurobiological markers for suicide risk in this population., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Mechanical thrombectomy (MT) is the standard of care in anterior circulation large vessel occlusion. A vital modifiable factor is successful reperfusion. While multiple passes improve the rates of successful reperfusion, previous studies have reported progressively diminishing returns. This study aimed to investigate the relationship between number of passes and outcomes in basilar artery occlusion (BAO)., Methods: This multicentre retrospective cohort study included patients who were treated with MT for acute BAO from eight comprehensive stroke centres between 2015 and 2020. The primary outcome was favourable functional outcome (FFO) defined as modified Rankin Scale (mRS) 0-3 measured at 90 days. Secondary outcomes included spontaneous intracranial haemorrhage and mortality. Patients were stratified according to reperfusion status and the number of passes for further analysis., Results: The adjusted odds ratio (OR) for FFO 90 days for each additional pass of a thrombectomy device was 0.56 ( P = 0.003). When ≤3 passes of the thrombectomy device were made, achieving reperfusion led to higher rates of FFOs. However, when >3 passes of the thrombectomy device were made, achieving reperfusion no longer led to higher rates of FFOs (FFO = 0% in patients who did not achieve reperfusion vs. FFO = 14.5 in patients who achieved reperfusion; P = 0.200). Notably, increasing number of passes was associated with a non-significant trend towards higher rate of parenchymal haemorrhage (OR 1.55, P = 0.055)., Conclusion: Acute BAO patients treated with up to three passes of a thrombectomy device derived improved functional outcomes from reperfusion compared to those with more than three passes. Further prospective cohort studies are necessary to validate these findings., (Copyright © 2025 Singapore Medical Journal.)

Neurostimulation delivers electrical pulses to modulate neuromuscular activity. Commonly used in medical interventions from pain relief to rehabilitation, neurostimulation typically uses manually placed hydrogel electrodes over the treated region. However, this method limits interventions requiring frequent, long-term daily use. To address this, novel fully textile electrodes are developed using industrial programmable knitting machines. These electrodes are designed to be washable, reusable, flexible, and breathable, with embedded interconnects. Textile electrodes are made of yarns with stainless steel and PEDOT-coated stainless steel conductive components. The electrodes' performance are compared with gel electrodes, characterizing impedance, sensorimotor stimulation thresholds, recruitment of induced movements, sensation levels, and perceived sensations. The effects of residential wash cycles and continuous use duration are also investigated. The proposed electrodes are found to perform similarly to hydrogel electrodes in all characterized metrics. No degradation in electrode performance is found after at least 30 wash cycles. Electrodes remained functionally intact after 1000 cycles of stretch loading at 50% of break strain. The textile electrodes consistently induced comfortable sensorimotor responses for at least six hours after donning. The proposed textile electrodes offer a novel and effective solution for neurostimulation interventions, paving the way for integration into smart garments and long-term wearable health technologies., (© 2024 Wiley‐VCH GmbH.)

The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals 1,2 , undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics 3,4 . Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints 5 , and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years. Haematological setpoints reflect a deep physiologic phenotype enabling investigation of acquired and genetic determinants of haematological regulation and its variation among healthy adults. Setpoints in apparently healthy adults were associated with significant variation in clinical risk: absolute risk of some common diseases and morbidities varied by more than 2% (heart attack and stroke, diabetes, kidney disease, osteoporosis), and absolute risk of all-cause 10 year mortality varied by more than 5%. Setpoints also define patient-specific reference intervals and personalize the interpretation of subsequent test results. In retrospective analysis, setpoints improved sensitivity and specificity for evaluation of some common conditions including diabetes, kidney disease, thyroid dysfunction, iron deficiency and myeloproliferative neoplasms. This study shows CBC setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults., Competing Interests: Competing interests: Mass General Brigham submitted a provisional patent application (63/695,679) on 17 September 2024, related to diagnostic and prognostic applications of haematological setpoints that includes B.H.F., M.T.R., V.T. and J.M.H. as inventors., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: Bipolar disorder (BD) and major depression have been associated with an increased risk of developing Parkinson's disease (PD); however, few studies have directly compared the risk of PD development between patients with BD and major depression while considering relevant risk factors and psychotropic medications., Methods: Using the Taiwan National Health Insurance Research Database, 21,186 patients with BD, 21,188 patients with major depression, and 42,374 controls were enrolled between 2001 and 2009, and followed until the end of 2011. Individuals who developed PD during the follow-up period were identified. Cox regression models were used to analyze the hazard ratio (HR) of developing PD, adjusting for demographic factors, comorbidities, and psychotropic medication usage., Results: Both patients with BD [HR 8.63, 95% confidence interval (CI) 6.35-11.72] and those with major depression (HR 5.68, 95% CI 4.15-7.78) had an elevated risk of subsequent PD compared to the controls. Patients with BD were associated with a 51% increased risk of subsequent PD compared with patients with major depression. Long-term treatment with antiepileptic mood stabilizers was associated with increased PD risk among patients with late-onset BD and high Charlson comorbidity index scores. Lithium was not associated with an increased PD risk., Conclusions: The study highlights an elevated PD risk in patients with BD and major depression compared to the controls, with BD patients at highest risk. Further research is needed to elucidate the complex interplay between psychotropic medications and neurodegenerative processes in BD, aiming to optimize therapeutic strategies and improve patient outcomes., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Guidelines suggest the Liver Imaging Reporting and Data System (LI-RADS) may not be applicable for some populations at risk for hepatocellular carcinoma (HCC). However, data assessing the association of HCC risk factors with LI-RADS major features are lacking. Purpose: To evaluate whether the association between HCC risk factors and each CT/MRI LI-RADS major feature differs among individuals at-risk for HCC. Methods: Databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched from 2014 to 2022. Individual participant data (IPD) were extracted from studies evaluating HCC diagnosis using CT/MRI LI-RADS and reporting HCC risk factors. IPD from studies were pooled and modelled with one-stage meta-regressions. Interactions were assessed between major features and HCC risk factors, including age, sex, cirrhosis, chronic hepatitis B virus (HBV), and study location. A mixed effects model that included the major features, as well as separate models that included interactions between each risk factor and each major feature, were fit. Differences in interactions across levels of each risk factor were calculated using adjusted odds-ratios (ORs), 95% confidence-intervals (CI), and z -tests. Risk of bias was assessed using QUADAS-2. (Protocol: https://osf.io/tdv7j/). Results: Across 23 studies (2958 patients and 3553 observations), the associations between LI-RADS major features and HCC were consistent across several HCC risk factors ( P -value range: .09-.99). A sensitivity analysis among the 4 studies with a low risk of bias did not differ from the primary analysis. Conclusion: The association between CT/MRI LI-RADS major features and HCC risk factors do not significantly differ in individuals at-risk for HCC. These findings suggest that CT/MR LI-RADS should be applied to all patients considered at risk by LI-RADS without modification or exclusions, regardless of the presence or absence of the risk factors evaluated in this study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Amit Singal has served as a consultant or on advisory boards for Genentech, AztraZeneca, Eisai, Exelixis, Bayer, Elevar, Boston Scientific, Sirtex, Histosonics, FujiFilm Medical Sciences, Exact Sciences, Roche, Abbott, Glycotest, Freenome, and GRAIL.

Background: We evaluated reporting of diagnostic test accuracy (DTA) systematic reviews using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-DTA and PRISMA-DTA for abstracts., Methods: We searched MEDLINE for recent DTA systematic reviews (September 2023-Mar 2024) to achieve a sample size of 100. Analyses evaluated adherence to PRISMA-DTA (and abstracts), on a per-item basis. Association of reporting with journal, country, impact factor (IF), index-test type, subspecialty area, use of supplemental material, PRISMA citation, word count, and PRISMA adoption was evaluated. Comparison to the baseline evaluation from 2019 was done. Protocol: https://doi.org/10.17605/OSF.IO/P25TE., Results: Overall adherence (n = 100) was 78% (20.3/26.0 items, SD = 2.0) for PRISMA-DTA and 52% (5.7/11.0 items, SD = 1.6) for abstracts. Infrequently reported items (<33% of studies): eligibility criteria, definitions for data extraction, synthesis of results, and characteristics of the included studies. Infrequently reported items in abstracts were characteristics of the included studies, strengths and limitations, and funding. Reporting completeness for full text was minimally higher in studies in higher IF journals [20.7 vs 19.8 items; 95% confidence interval (95%CI) (0.09; 1.77)], as well as studies that cited PRISMA [21.1 vs 20.1 items; 95%CI (0.04; 1.95)], or used supplemental material (20.7 vs 19.2 items; 95%CI (0.63; 2.35)]. Variability in reporting was not associated with author country, journal, abstract word count limitations, PRISMA adoption, structured abstracts, study design, subspecialty, open-access status, or index test. No association with word counts was observed among full text or abstracts. Compared to the baseline evaluation, reporting was improved for full texts [71% to 78%; 95%CI (1.18; 2.26)] but not for abstracts [50% to 52%; 95%CI (-0.20; 0.60)]., Conclusions: Compared to the baseline evaluation published in 2019, we observed modest improved adherence to PRISMA-DTA and no improvement in PRISMA-DTA for abstracts reporting., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background:  Stent misdeployment (SMD) is a feared and poorly characterized technical challenge of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) using lumen-apposing stents. We aimed to ascertain the rate of stent misdeployment in EUS-CDS for malignant distal biliary obstruction (MDBO) and describe its outcomes while identifying variables associated with its occurrence., Method:  This was a post hoc analysis of two randomized controlled trials comparing EUS-CDS vs. endoscopic retrograde cholangiopancreatography in MDBO. The primary end point was rate of SMD, classified as misdeployment of the distal flange (type I), proximal flange (type II), contralateral bile duct wall injury (type III), or double mucosal puncture (type IV). Multivariable analysis was performed to identify variables associated with SMD and/or technical failure, and with clinical failure or stent dysfunction., Results:  152 patients were included. Technical success was 93.4 %. SMD occurred in 11 patients (7.2 %; 95 %CI 3.1 %-11.4 %): 8 type I, 1 type II, and 2 type III. Endoscopic salvage of SMD was successful in 81.8 %. Misdeployment led to adverse events in four patients (two mild, two moderate), giving an overall SMD-related adverse event rate of 2.6 % (95 %CI 0.7 %-6.6 %). On multivariable analysis, extrahepatic bile duct diameter of ≤ 15 mm was associated with increased odds of SMD and/or technical failure., Conclusion:  SMD was relatively common in EUS-CDS and was associated with an extrahepatic bile duct diameter of ≤ 15 mm. The majority of misdeployments could be rescued endoscopically with low risk for adverse events., Competing Interests: Y.I. Chen is a consultant for Boston Scientific, has received research funding from Boston Scientific, and is the co-founder of Chess Medical Inc. A. Sahai is a consultant for Boston Scientific and Pentax. B. Napoleon has received honoraria for proctoring endoscopy training from Maunea Kea, Boston Scientific, Olympus, and TaeWoong Medical. R. Kunda is a consultant for Boston Scientific, Olympus, M.I.Tech, Omega Medical Imaging, Q3 Medical-AMG International, and EndoGastric Solutions. N. Forbes is a consultant and speaker for Boston Scientific and Pentax Medical, a speaker for AstraZeneca, and has received research funding from Pentax Medical. A.Y.B. Teoh is a consultant for Boston Scientific, Cook, TaeWoong Medical, Microtech, and M.I.Tech. The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Childhood cancer survivors are at increased lifetime risk of morbidity and mortality, but adherence to periodic surveillance is suboptimal. One of the reasons that adult survivors of childhood cancer do not complete the recommended surveillance is that their parents may not have disclosed their cancer history to them. We sought to identify key barriers and enablers to talking to children about their cancer history., Method: Semi-structured interviews were completed with parents of childhood cancer survivors who had delayed telling their child about their cancer diagnosis. The theoretical domain framework (TDF) informed the interview guide and analysis. Interview transcripts were coded line-by-line and mapped to domains in accordance with the framework., Results: Twelve interviews were conducted with parents of childhood cancer survivors. Parents expressed a desire to protect their children from the knowledge and awareness that they had cancer, as they thought it could lead to hypervigilance and impact their child's identity (TDF domain: belief about consequences). Parents were also afraid the conversation would "trigger" emotions for themselves related to the time their child had cancer (emotion). Due to these barriers, it was the influence of the clinical team that was described as the driving push to having this difficult conversation (social influences). Parents also had a strong conviction that their child had the right to know and that they could use this information to protect themselves and stay healthy (motivation)., Discussion: Parents thought telling their child they had cancer was important because "knowledge is power" and their child "has the right to know." However, this was a difficult conversation that was often avoided., Implications for Cancer Survivors: This study confirms the need for an intervention that encourages and supports parents to have this difficult conversation with their child., Competing Interests: Declarations. Ethics approval: The study was approved by The Hospital for Sick Children Research Ethics Board (Protocol # 1000076291) and Women’s College Hospital REB (#: 2020–0108-E). Consent to participate: All participants gave informed consent to participate in the research study. Consent for publication: All participants gave informed consent that the data we received could be published. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Semi-biological photosynthesis combines synthetic photosensitizers with microbial catalysts to produce sustainable fuels and chemicals from CO 2 . However, the inefficient transfer of photoexcited electrons to microbes leads to limited CO 2 utilization, restricting the catalytic performance of such biohybrid assemblies. Here, we introduce a biological engineering solution to address the inherently sluggish electron uptake mechanism of a methanogen, Methanosarcina barkeri (M. barkeri), by coculturing it with an electron transport specialist, Geobacter sulfurreducens KN400 (KN400), an adapted strain rich with multiheme c-type cytochromes (c-Cyts) and electrically conductive protein filaments (e-PFs) made of polymerized c-Cyts with enhanced capacity for extracellular electron transfer (EET). Integration of this M. barkeri-KN400 co-culture with a synthetic photosensitizer, carbon nitride, demonstrates that c-Cyts and e-PFs, emanating from live KN400, transport photoexcited electrons efficiently from the carbon nitride to M. barkeri for methanogenesis with remarkable long-term stability and selectivity. The demonstrated cooperative interaction between two microbes via direct interspecies electron transfer (DIET) and the photosensitizer to assemble a semi-biological photocatalyst introduces an ecosystem engineering strategy in solar chemistry to drive sustainable chemical reactions., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background and Purpose: Clinicians use the CTCAE scale to grade radiation dermatitis (RD) based on edema, erythema, and desquamation. The purpose of this study was to correlate the CTCAE scores with the severity of patient-reported symptoms using a skin symptom assessment (SSA) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS)., Materials and Methods: This is a secondary analysis of a randomized controlled trial involving 376 patients receiving Mepitel Film or standard-of-care for RD prophylaxis. The highest symptom categories for SSA and patient-component RISRAS assessments were selected from all time points, and a summary analysis and Spearman correlation coefficient was calculated for patients with CTCAE Grades 0, 1, 2, 3, and Grade 2/3, respectively. Analyses were conducted across all patients, within each treatment arm, and between arms in patients with only Grade 2 or 3 toxicity., Results: Weak correlations between CTCAE scores and all patient-reported skin symptoms were found across the entire cohort and each treatment arm (p < 0.05). Patients with Grade 2 (n = 72) and Grade 3 RD (n = 24) reported similar rates of patient-reported moderate-to-severe skin symptoms (11-72% vs 14-79%), with no significant difference in rates of individual moderate-to-severe symptom between these cohorts (p > 0.05). Between treatment arms, rates of patient-reported moderate-to-severe scores were similar for most symptoms., Conclusion: CTCAE RD scores are weakly correlated with patient-reported skin symptoms and cannot distinguish between patients with severe patient-reported outcomes. Clinicians should consider the limitations of CTCAE grading and incorporate patient-reported outcomes within clinical practice., Competing Interests: Declarations Ethics approval This research was conducted in accordance with the Declaration of Helsinki. Human ethics and consent to participate declarations were not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Clinical concussion assessments do not typically simulate the speed or complexity of sport. Performance changes arising from combined physical, cognitive, and sensory demands of sport may thus remain undetected during rehabilitation. We developed R2Play, a multidomain return-to-play assessment tool for youth with concussions. R2Play involves levels and conditions that vary in physical, cognitive, and sensory load to simulate the multidomain demands of sport., Objectives: To explore cross-site feasibility, face validity, and content validity of R2Play by integrating quantitative and qualitative data., Methods: Convergent mixed-methods feasibility study. Five sites will each recruit 5 clinicians (total nc = 25) and 10 youth sport participants (ages 10-25 y) with a history of concussion in the previous year (total ny = 50). Feasibility will be evaluated using quantitative criteria for acceptability, demand, implementation, practicality, and integration, and qualitative investigated data from content analysis of postassessment interviews with youth and clinician participants. Face validity will be investigated in postassessment interviews. Content validity will be established through (1) changes in performance metrics (time to completion, errors, and heart rate) across R2Play levels, (2) youth-perceived physical and cognitive exertion for each level, and (3) overall clinician perceptions determined through postassessment interviews. Qualitative and quantitative data will be merged through joint display to identify areas of convergence, divergence, and complementarity, and to establish meta-inferences about feasibility, face validity, and content validity., Discussion: This study aims to demonstrate the face and content validity of R2Play, and its feasibility for cross-site implementation. Findings will guide further iteration of R2Play and establish the foundation for a larger multicenter validation study to establish the psychometric properties of R2Play. This work represents an important first step toward the implementation of an ecologically valid multidomain assessment tool designed to support a safe and efficient return-to-play after concussion, ultimately reducing the risk of recurrent concussion and subsequent injury.

Background and Purpose: The study evaluated the concordance between patient-reported outcomes (PRO) and clinician-reported outcomes (CRO) of acute radiation dermatitis (RD) symptoms following adjuvant radiotherapy for early-stage and locally advanced breast cancer., Material and Methods: This is a secondary analysis of a multi-center randomized phase 3 trial (376 patients). Ordinal logistic regression analysis was used to compare the Skin Symptom Assessment (SSA) independently reported by both patients and clinicians. Concordance between patient- and clinician-reported SSAs for RD symptoms was measured by percent concordance, concordance index (C-statistic), and Cohen's Kappa. Analyses were performed across all patients in the original modified intention-to-treat analysis and those with only grade 2-3 (CTCAE) RD., Results: PROs were significantly more severe than CROs across all RD symptoms (Odds Ratio [OR] > 1; p < 0.0001). Pigmentation (OR 5.4), blistering/peeling (OR 4.0), and pain/soreness (OR 3.9) were the most differentially reported symptoms. Poor-to-low concordance was noted between patient- and clinician-reported SSAs for all RD symptoms for the entire cohort (percent concordance < 50%, C-statistic 0.52-0.63, Cohen's Kappa 13.9-23.4%) and those with grade 2-3 RD (percent concordance < 50%, C-statistic 0.56-0.66, Cohen's Kappa 2.0-24.5%). Similarly, poor-to-low concordance was noted in both Mepitel film and standard-of-care arms., Conclusion: PROs and CROs have poor concordance in breast RD, and patients report worse outcomes than clinicians, regardless of RD severity or prophylaxis. PROs must be further integrated into routine clinical practice and clinical trial design to reduce the risk of underreporting symptoms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Impaired consciousness is associated with complications and mortality in COVID-19 patients. We study factors associated with impaired consciousness as measured by the Glasgow Coma Scale (GCS) in COVID-19 patients., Methods: This is a retrospective study of 604 patients with COVID-19 in the metropolitan New York City area. We study the association of demographics, comorbidity, disease severity, treatment management, and laboratory measurements with both GCS nadir during hospitalization and GCS at discharge., Results: Age was significantly associated with severe GCS nadir during hospitalization and at hospital discharge. Body mass index comorbidity was significantly associated with severe GCS at hospital discharge. Sedation treatment was significantly associated with both moderate and severe GCS nadir during hospitalization. Glucose nadir was significantly associated with severe GCS nadir during hospitalization. Sodium level at admission was associated with decreased relative risk while BUN peak level during hospitalization was associated with increased relative risk for severe GCS on discharge., Conclusion: We found that factors from demographics, comorbidity, treatment management, and laboratory measurements were associated with GCS while disease severity was not significantly associated with GCS. These findings can guide clinicians for treatment approaches for the early identification of impaired consciousness and its degrees of severity in COVID-19 patients., Competing Interests: Conflict of interest: The authors have no conflict of interest., (© 2024 Greater Baltimore Medical Center.)

Objective: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252., Methods: GO-VIVA participants who continued IV golimumab (80 mg/m 2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data., Results: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 μg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively., Conclusion: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile., (Copyright © 2024 by the Journal of Rheumatology.)

Background: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release., Methods: A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3., Findings: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3., Conclusion: BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies., Competing Interests: Declarations Competing interests The authors declare no competing interests. Disclosures Y.S., L.E.H.S, and T.W. are inventors on patent applications filed by Boston Children’s Hospital. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Objectives: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scv o2 ) in estimating mixed venous oxygen saturation (Sv o2 ) and cardiac index in critically ill patients., Data Sources: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024., Study Selection: Studies of patients in the ICU for whom Scv o2 and at least one reference standard test was performed (thermodilution and/or Sv o2 ) were included., Data Extraction: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Sv o2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments., Data Synthesis: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Sv o2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Sv o2 was 0.83 (95% CI, 0.75-0.89) with a mean difference of 2.98% toward Scv o2 . The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46-0.48; p < 0.0001)., Conclusions: There is moderate reliability for Scv o2 in predicting Sv o2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scv o2 in predicting cardiac index., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Objective: Randomized controlled trials (RCTs) inform health-care decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesize all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project is developing a tool to identify problematic RCTs in systematic reviews of health care-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion., Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorized these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list., Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool., Conclusion: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool., Competing Interests: Declaration of competing interest J.W., CH, GAA., L.B., and J.J.K. declare funding from NIHR (NIHR203568) in relation to the current project. J.W. additionally declares Stats or Methodological Editor roles for BJOG, Fertility and Sterility, Reproduction and Fertility, Journal of Hypertension, and for Cochrane Gynecology and Fertility. C.H. declares a Statistical Editor role for Cochrane Colorectal. L.B. additionally declares a role as Academic Meta-Research Editor for PLoS Biology, and that The University of Colorado receives remuneration for service as Senior Research Integrity Editor, Cochrane. J.J.K. additionally declares a Statistical Editor role for The BMJ. A.A. declares that The Health Services Research Unit, University of Aberdeen, is funded by the Health and Social Care Directorates of the Scottish Government. V.B. is EiC of the Medical Journal of Australia and on the Editorial Board of Research Integrity and Peer Review. N.J.L.B. declares roles as Editorial Board member for International Review of Social Pyschology/Revue Internationale de Psychologie Sociale, Statistical Advisory Board member for Mental Health Science, and Advisory Board member for Meta-Psychology. M.C. declares that he is Co-ordinating Editor for the Cochrane Methodology Review Group, Editor in Chief, Journal of Evidence-Based Medicine, and Coordinating Editor, James Lind Library. E.F., S.G., and T.La. declare employment by Cochrane. E.F. additionally declares a role as Editorial Board member for Cochrane Synthesis and Methods. T.La. additionally declares authorship of a chapter in the Cochrane Handbook for Systematic Reviews of Interventions and that he is a developer of standards for Cochrane intervention reviews (MECIR). T.Li. is funded by the National Eye Institute, National Institutes of Health (Grant #UG1 EY020522). S.L. is funded by NHMRC (APP1195189), and holds general or methodological editor positions for Cochrane Gynecology and Fertility, Fertility and Sterility, and Human Reproduction. A.L. is on the editorial board of BMC Medical Ethics. B.W.M. declares roles as Editor for Cochrane Gynecology and Fertility and Sexually Transmitted Infections, and for Fertility and Sterility. S.L. declares roles as Associate Editor for Human Reproduction, Methodological Editor for Fertility and Sterility, and Editor for Cochrane Gynecology and Fertility. N.O.C. is a member of the Cochrane Editorial Board and holds an ERA-NET Neuron Cofund grant for a separate project. A.L.S. declares funding from Australian National Health and Medical Research Council Investigator Grants (GNT2009432). E.S. is a Sign-off Editor for the Cochrane Library. M.v.W. is coordinating editor of Cochrane Gynecology and Fertility and Cochrane Sexually Transmitted Infections, Methodological Editor of Human Reproduction Update and editorial Editor of Fertility and Sterility. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used - however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25-7.25) to 0 (IQR 0-0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031., (© 2024. The Author(s).)

Purpose: Use a tailored version of the Quality Assessment of Diagnostic Accuracy Studies tool to evaluate risk of bias and applicability across LIRADS related publications. Method: A tailored QUADAS-2 tool was created through consensus approach to assess risk of bias and applicability across 37 LI-RADS related publications. Studies were selected from 2017 to 2022 using the assistance of experienced hospital librarians to search for studies evaluating the diagnostic accuracy of CT, MRI, or contrast-enhanced ultrasound for HCC using LI-RADS through multiple different databases. QUADAS-2 assessments were performed in duplicate and independently by 2 authors with experience using the QUADAS-2 tool. Disagreements were resolved with a third expert reviewer. Consensus QUADAS-2 assessments were tabulated for each domain. Results: Using the tailored QUADAS-2 tool, 31 of the 37 included LI-RADS studies were assessed as high risk of bias, and 9 out of 37 studies demonstrated concerns for applicability. Patient selection (21 out of 37 studies) and flow/timing (24 out of 37 studies) domains demonstrated the highest risk of bias. 6 out of 37 studies in the index domain demonstrated high risk of bias. 2 out of 37 studies showed high risk of bias in the reference standard domain. Conclusion: A significant proportion of LI-RADS research is at risk of bias with concerns for applicability. Identifying risk of bias in such research is essential to recognize limitations of a study that may affect the validity of the results. Areas for improvement in LI-RADS research include reducing selection bias, avoiding inappropriate exclusions, and decreasing verification bias., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO)., Materials and Methods: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs., Results: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9)., Conclusions: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The Liver Imaging Reporting and Data System (LI-RADS) does not consider factors extrinsic to the observation of interest, such as concurrent LR-5 observations., Purpose: To evaluate whether the presence of a concurrent LR-5 observation is associated with a difference in the probability that LR-3 or LR-4 observations represent hepatocellular carcinoma (HCC) through an individual participant data (IPD) meta-analysis., Methods: Multiple databases were searched from 1/2014 to 2/2023 for studies evaluating the diagnostic accuracy of CT/MRI for HCC using LI-RADS v2014/2017/2018. The search strategy, study selection, and data collection process can be found at https://osf.io/rpg8x . Using a generalized linear mixed model (GLMM), IPD were pooled across studies and modeled simultaneously with a one-stage meta-analysis approach to estimate positive predictive value (PPV) of LR-3 and LR-4 observations without and with concurrent LR-5 for the diagnosis of HCC. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)., Results: Twenty-nine studies comprising 2591 observations in 1456 patients (mean age 59 years, 1083 [74%] male) were included. 587/1960 (29.9%) LR-3 observations in 1009 patients had concurrent LR-5. The PPV for LR-3 observations with concurrent LR-5 was not significantly different from the PPV without LR-5 (45.4% vs 37.1%, p = 0.63). 264/631 (41.8%) LR-4 observations in 447 patients had concurrent LR-5. The PPV for LR-4 observations with concurrent LR-5 was not significantly different from LR-4 observations without concurrent LR-5 (88.6% vs 69.5%, p = 0.08). A sensitivity analysis for low-risk of bias studies (n = 9) did not differ from the primary analysis., Conclusion: The presence of concurrent LR-5 was not significantly associated with differences in PPV for HCC in LR-3 or LR-4 observations, supporting the current LI-RADS paradigm, wherein the presence of synchronous LR-5 may not alter the categorization of LR-3 and LR-4 observations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective:  Nipocalimab is a neonatal fragment crystallizable (Fc) receptor (FcRn)-blocking monoclonal antibody that inhibits placental immunoglobulin G (IgG) transfer and lowers circulating maternal IgG levels. In an open-label, single-arm, phase 2 study, nipocalimab demonstrated evidence of safety and efficacy that support further investigation in a pivotal phase 3 trial of recurrent hemolytic disease of the fetus and newborn (HDFN). The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN, defined as HDFN associated with poor fetal outcomes or neonatal death., Study Design:  AZALEA is a multicenter, randomized, placebo-controlled, double-blind, phase 3 study enrolling alloimmunized pregnant individuals ( N ≈ 120) at risk for severe HDFN based on obstetric history. Participants are randomized 2:1 to receive intravenous 45 mg/kg nipocalimab or placebo weekly from 13-16 to 35 weeks gestational age (GA). During the double-blind treatment period, participants receive standard-of-care weekly monitoring for fetal anemia until planned delivery at 37 to 38 weeks of GA. Postnatal follow-up periods are 24 weeks for maternal participants and 104 weeks for neonates/infants., Results:  The primary endpoint is the proportion of pregnancies that do not result in intrauterine transfusion (IUT), hydrops fetalis, or fetal loss/neonatal death from all causes. Key secondary endpoints include the severity of HDFN as measured by a composite HDFN severity index, the earliest time to occurrence of IUT or hydrops fetalis, the modified neonatal mortality and morbidity index in liveborn neonates, and the number of IUTs received. Other endpoints are safety, patient- and caregiver-reported outcomes, pharmacokinetics, pharmacodynamics (e.g., IgG, FcRn receptor occupancy), and immunogenicity of nipocalimab., Conclusion:  AZALEA, the first placebo-controlled, randomized, multicenter, prospective trial in severe HDFN, is designed to evaluate the safety and efficacy of nipocalimab, a potential preventive and noninvasive intervention, in at-risk HDFN pregnancies., Key Points: · Severe HDFN leads to poor fetal/neonatal outcomes.. · IUTs are associated with complications and fetal loss.. · Nipocalimab blocks IgG recycling and placental transfer.. · Nipocalimab reduces fetal anemia and IUTs in early-onset severe HDFN.. · The phase 3 AZALEA study evaluates nipocalimab in severe HDFN.., Competing Interests: Y.K., P.A., E. Lam, J.H.L., L.E.L., R.M.N., V.O., S.S-K., M.L.T., J.Z., U.A., and W.S. are employees of Janssen and hold stock/stock options from Johnson & Johnson. E.J.T.V. serves as the principal investigator of the UNITY, CLARITY, and AZALEA studies in The Netherlands. E.T., E. Lopriore, and D.O. received consulting fees for membership of steering committees and advisory boards for clinical studies from Momenta Pharmaceuticals, Inc., and Janssen Pharmaceuticals, Inc. K.J.M. serves as the overall principal investigator for the phase 2 trial of nipocalimab (UNITY); received funding from Momenta Pharmaceuticals, Inc., paid on his behalf to the McGovern Medical School – UT Health; received funding from Janssen Pharmaceuticals, Inc., paid on his behalf to Dell Medical School at The University of Texas at Austin for a clinical trial on a monoclonal antibody for the treatment of HDFN; served on the steering committees and advisory boards for clinical studies for Momenta Pharmaceuticals, Inc., and Janssen Pharmaceuticals, Inc., but has not received funding for these activities; received royalty funding from UpToDate, Inc., for authorship of various chapters; received consulting fees from Health Management Associates, Inc., for consultation on the formation of fetal centers; received consulting fees from BillionToOne, Inc., paid on his behalf to Dell Medical School at The University of Texas at Austin; received honoraria from GLC Healthcare, Inc., for podcast content on HDFN; and serves as a nonpaid consultant for immunology at Janssen Pharmaceuticals, Inc., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers., Objectives: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population., Methods: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy ® OMNI ® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching., Results: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes., Conclusions: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization., (© 2024. The Author(s).)

A simple and precious-metal free photosystem for the reduction of aqueous CO 2 to syngas (CO and H 2 ) is reported consisting of carbon dots (CDs) as the sole light harvester together with a molecular cobalt bis(terpyridine) CO 2 reduction co-catalyst. This homogeneous photocatalytic system operates in the presence of a sacrificial electron donor (triethanolamine) in DMSO/H 2 O solution at ambient temperature. The photocatalytic system exhibits an activity of 7.7 ± 0.2 mmol syngas g CDs -1 (3.6 ± 0.2 mmol CO g CDs -1 and 4.1 ± 0.1 mmol H2 g CDs -1 ) after 24 hours of full solar spectrum irradiation (AM 1.5G). Spectroscopic and electrochemical characterization supports that this photocatalytic performance is attributed to a favorable association between CDs and the molecular cobalt catalyst, which results in improved interfacial photoelectron transfer and catalytic mechanism. This work provides a scalable and inexpensive platform for the development of CO 2 photoreduction systems using CDs., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Purpose: Fibroblast activation protein (FAP)-inhibitor (FAPI)-PET tracers allow imaging of the FAP-expressing cancer associated fibroblasts (CAF) and also the normal activated fibroblasts (NAF) involved in inflammation/fibrosis that may be present after invasive medical interventions. We evaluated [68Ga]Ga-FAPI-46 uptake patterns post-medical/invasive non-systemic interventions., Methods: This single-center retrospective analysis was conducted in 79 consecutive patients who underwent [ 68 Ga]Ga-FAPI-46 PET/CT. Investigators reviewed prior patient medical/invasive interventions (surgery, endoscopy, biopsy, radiotherapy, foreign body placement (FBP) defined as implanted medical/surgical material present at time of scan) and characterized the anatomically corresponding FAPI uptake intensity both visually (positive if above surrounding background) and quantitatively (SUVmax). Interventions with missing data/images or confounders of [ 68 Ga]Ga-FAPI-46 uptake (partial volume effect, other cause of increased uptake) were excluded. Available correlative FDG, DOTATATE and PSMA PET/CTs were analyzed when available., Results: 163 medical/invasive interventions (mostly surgeries (49%), endoscopies (18%) and non-surgical biopsies (10%)) in 60 subjects were included for analysis. 43/163 (26%) involved FBP. FAPI uptake occurred in 24/163 (15%) of interventions (average SUVmax 3.2 (mild), range 1.5-5.1). The median time-interval post-intervention to FAPI-PET was 47.5 months and was shorter when FAPI uptake was present (median 9.5 months) than when absent (median 60.1 months; p = 0.001). Cut-off time beyond which no FAPI uptake would be present post-intervention without FBP was 8.2 months, with a sensitivity, specificity, positive predictive value and negative predictive value of 82, 90, 99 and 31% respectively. No optimal cutoff point could be determined when considering interventions with FBP. No significant difference was detected between frequency of [ 68 Ga]Ga-FAPI-46 and [ 18 F]FDG uptake in intervention sites. Compared to [ 68 Ga]Ga-PSMA-11, [ 68 Ga]Ga-FAPI-46 revealed more frequent and intense post-interventional tracer uptake., Conclusion: [ 68 Ga]Ga-FAPI-46 uptake from medical/invasive interventions without FBP appears to be time dependent, nearly always absent beyond 8 months post-intervention, but frequently present for years with FBP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: LI-RADS version 2018 (v2018) is used for non-invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI-RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI-RADS category 5 (definite HCC) for HCC. However, mLI-RADS requires multicenter validation., Purpose: To evaluate the performance of v2018 and mLI-RADS for liver lesions in a large, heterogeneous, multi-national cohort of patients at risk for HCC., Study Type: Systematic review and meta-analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]., Population: 2223 observations from 1817 patients (includes all LI-RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI-RADS population criteria) from 12 retrospective studies., Field Strength/sequence: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat-suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion-weighted imaging was used when available., Assessment: Liver observations were categorized using v2018 and mLI-RADS. The diagnostic performance of each system's category 5 (LR-5 and mLR-5) for HCC were compared., Statistical Tests: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05., Results: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR-5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC., Data Conclusion: This study confirms mLR-5 has higher sensitivity than LR-5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI-RADS proposal in a heterogeneous, international cohort., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: In recent years, multiple guidelines on bariatric and metabolic surgery were published, however, their quality remains unknown, leaving providers with uncertainty when using them to make perioperative decisions. This study aims to evaluate the quality of existing guidelines for perioperative bariatric surgery care., Methods: A comprehensive search of MEDLINE and EMBASE were conducted from January 2010 to October 2022 for bariatric clinical practice guidelines. Guideline evaluation was carried out using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework., Results: The initial search yielded 1483 citations, of which, 26 were included in final analysis. The overall median domain scores for guidelines were: (1) scope and purpose: 87.5% (IQR: 57-94%), (2) stakeholder involvement: 49% (IQR: 40-64%), (3) rigor of development: 42.5% (IQR: 22-68%), (4) clarity of presentation: 85% (IQR: 81-90%), (5) applicability: 6% (IQR: 3-16%), (6) editorial independence: 50% (IQR: 48-67%), (7) overall impressions: 48% (IQR: 33-67%). Only six guidelines achieved an overall score >70%., Conclusions: Bariatric surgery guidelines effectively outlined their aim and presented recommendations. However, many did not adequately seek patient input, state search criteria, use evidence rating tools, and consider resource implications. Future guidelines should reference the AGREE II framework in study design., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Single-cell genomics permits a new resolution in the examination of molecular and cellular dynamics, allowing global, parallel assessments of cell types and cellular behaviors through development and in response to environmental circumstances, such as interaction with water and the light-dark cycle of the Earth. Here, we leverage the smallest, and possibly most structurally reduced, plant, the semiaquatic Wolffia australiana , to understand dynamics of cell expression in these contexts at the whole-plant level. We examined single-cell-resolution RNA-sequencing data and found Wolffia cells divide into four principal clusters representing the above- and below-water-situated parenchyma and epidermis. Although these tissues share transcriptomic similarity with model plants, they display distinct adaptations that Wolffia has made for the aquatic environment. Within this broad classification, discrete subspecializations are evident, with select cells showing unique transcriptomic signatures associated with developmental maturation and specialized physiologies. Assessing this simplified biological system temporally at two key time-of-day (TOD) transitions, we identify additional TOD-responsive genes previously overlooked in whole-plant transcriptomic approaches and demonstrate that the core circadian clock machinery and its downstream responses can vary in cell-specific manners, even in this simplified system. Distinctions between cell types and their responses to submergence and/or TOD are driven by expression changes of unexpectedly few genes, characterizing Wolffia as a highly streamlined organism with the majority of genes dedicated to fundamental cellular processes. Wolffia provides a unique opportunity to apply reductionist biology to elucidate signaling functions at the organismal level, for which this work provides a powerful resource., (© 2024 Denyer et al.; Published by Cold Spring Harbor Laboratory Press.)

Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease., (© 2024. The Author(s).)

Objective: To pragmatically assess the clinical and cost-effectiveness of water fluoridation for preventing dental treatment and improving oral health in a contemporary population of adults and adolescents, using a natural experiment design., Methods: A 10-year retrospective cohort study (2010-2020) using routinely collected NHS dental treatment claims data. Participants were patients aged 12 years and over, attending NHS primary dental care services in England (17.8 million patients). Using recorded residential locations, individuals exposed to drinking water with an optimal fluoride concentration (≥0.7 mg F/L) were matched to non-exposed individuals using propensity scores. Number of NHS invasive dental treatments, DMFT and missing teeth were compared between groups using negative binomial regression. Total NHS dental treatment costs and cost per invasive dental treatment avoided were calculated., Results: Matching resulted in an analytical sample of 6.4 million patients. Predicted mean number of invasive NHS dental treatments (restorations 'fillings'/extractions) was 3% lower in the optimally fluoridated group (5.4) than the non-optimally fluoridated group (5.6) (IRR 0.969, 95% CI 0.967, 0.971). Predicted mean DMFT was 2% lower in the optimally fluoridated group (IRR 0.984, 95% CI 0.983, 0.985). There was no difference in the predicted mean number of missing teeth per person (IRR 1.001, 95% CI 0.999, 1.003) and no compelling evidence that water fluoridation reduced social inequalities in dental health. Optimal water fluoridation in England 2010-2020 was estimated to cost £10.30 per person (excludes initial set-up costs). NHS dental treatment costs for optimally fluoridated patients 2010-2020 were 5.5% lower, by £22.26 per person (95% CI -£21.43, -£23.09)., Conclusions: Receipt of optimal water fluoridation 2010-2020 resulted in very small positive health effects which may not be meaningful for individuals. Existing fluoridation programmes in England produced a positive return on investment between 2010 and 2020 due to slightly lower NHS dental care utilization. This return should be evaluated against the projected costs and lifespan of any proposed capital investment in water fluoridation, including new programmes., (© 2024 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Background: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD., Methods: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections., Results: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5)., Conclusion: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Background: Inhaler education for patients with asthma and patients with COPD is typically provided by non-pulmonologists. We studied inhaler education by pulmonologists to determine changes in clinical outcomes and inhaler use., Methods: This was a retrospective study of 296 subjects diagnosed with asthma, COPD, or both that evaluated use of inhaler technique education and its impact on (1) inhaler/dosage change consisting of dosage change in the same class of inhaler and/or change in number of inhalers, (2) forced expiratory volume in one second/forced vital capacity (FEV 1 /FVC%), (3) disease symptom control, (4) out-patient visits, (5) urgent care visits (6) emergency department visits, and (7) hospital admissions. One group received inhaler technique education by a pulmonologist while the other group did not., Results: The pulmonologist inhaler technique-educated group had significantly decreased relative risk for inhaler/dosage increase (relative risk 0.57 [95% CI 0.34-0.96], P = .03) and significantly increased odds for symptom control (odds ratio 2.15 [95% CI 1.24-3.74], P = .01) at 1-y follow-up as compared to the no education group. No differences occurred for FEV 1 /FVC%, out-patient visits, urgent care visits, emergency department visits, and hospital admissions., Conclusions: Pulmonologist education of inhaler technique for patients with asthma and patients with COPD was associated with decreased relative risk for inhaler/dosage increase and increased odds for symptom control. We recommend pulmonologists provide education of inhaler technique to patients with asthma and patients with COPD and not rely on non-pulmonologist education alone. Prospective research is needed to confirm the importance of proper inhaler techniques., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objective: To explore markers that reflect sleep-disordered breathing (SDB) severity and investigate their associations with cardiometabolic risk factors in adolescents and young adults., Methods: Participants were recruited from our SDB epidemiological cohort. They underwent overnight polysomnography and ambulatory blood pressure (BP) monitoring. Complete blood count, ferritin, high-sensitivity C-reactive protein (hs-CRP), fasting blood glucose, and lipid profile were measured. Multiple linear regression was used to examine the association between red cell indices (RCIs), ferritin, and obstructive apnea-hypopnea index (OAHI). Subgroup analyses on participants with SDB were performed for the association of RCIs and ferritin with lipid profile, hs-CRP, and BP., Results: There were 88 participants with SDB and 155 healthy controls aged 16-25 years. Hemoglobin (Hb; p  < .001), hematocrit (HCT; p  < .001), and ferritin ( p  < .001) were elevated with increasing SDB severity and were independently associated with OAHI (β=1.06, p  < .001; β =40.2, p  < .001; β =4.89 × 10 -3 , p  = .024, respectively). In participants with SDB, after adjusting for age, sex, and BMI, significant associations were found between ferritin with low-density lipoprotein (LDL; β =0.936 × 10 -3 , p  = .008) and triglyceride (TG; β =1.08 × 10 -3 , p  < .001), as well as between Hb ( β =1.40, p  = .007), HCT ( β =51.5, p  = .010) and mean arterial pressure (MAP). Ferritin ( β =0.091, p  = .002), Hb ( β =0.975, p  = .005), and HCT ( β =38.8, p  = .004) were associated with hs-CRP independent of age, sex, BMI, plasma LDL, and MAP. OAHI was not associated with LDL and TG in the multivariable models., Conclusions: Serum ferritin, but not OAHI, was associated with LDL and TG in participants with SDB, suggesting it is a potential marker of cardiometabolic risk in patients with SDB., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Medical imaging diagnostic test accuracy research is strengthened by adhering to best practices for study design, data collection, data documentation, and study reporting. In this review, key elements of such research are discussed, and specific recommendations provided for optimizing diagnostic accuracy study execution to improve uniformity, minimize common sources of bias and avoid potential pitfalls. Examples are provided regarding study methodology and data collection practices based on insights gained by the liver imaging reporting and data system (LI-RADS) individual participant data group, who have evaluated raw data from numerous MRI diagnostic accuracy studies for risk of bias and data integrity. The goal of this review is to outline strategies for investigators to improve research practices, and to help reviewers and readers better contextualize a study's findings while understanding its limitations. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: The impact of pancreaticoduodenectomy on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who had previously undergone pancreaticoduodenectomy., Materials and Methods: A single 10-mg dose of apixaban was administered to 4 volunteers who underwent pancreaticoduodenectomy at least 6 months prior. The maximum plasma apixaban concentration (C max ) and area under the plasma concentration time-curve (AUC 0-24 , AUC 0-inf ) were compared against healthy historical control subjects (N = 12). Geometric mean ratios (GMR) with 90% confidence interval (CI) were calculated for determination of comparative bioequivalence., Results: In pancreaticoduodenectomy patients, AUC 0-24 and AUC 0-inf were 1,861 and 2,080 ng×h/mL, respectively. The GMRs of AUC 0-24 and AUC 0-inf between study subjects and healthy controls were 1.27 (90% CI 0.88 - 1.83) and 1.18 (90% CI 0.82 - 1.72). The mean C max of apixaban was 201 ng/mL (SD 15.6) occurring at a median t max of 3.25 hours (range 2.5 - 4 hours). The GMR of C max between study subjects and healthy controls was 1.12 (90% CI 0.77 - 1.63)., Conclusion: The pharmacokinetic characteristics of apixaban in subjects who had undergone pancreaticoduodenectomy are not significantly different from those of healthy controls. Though the sample size of this study is small, results suggest that no change to apixaban dose regimen is needed in patients who have had a pancreaticoduodenectomy.

This multicenter randomized phase III trial (NCT04457245) evaluated the effect of performing prostate-specific membrane antigen (PSMA) PET/CT before definitive radiotherapy. Methods: Men with unfavorable intermediate- or high-risk prostate cancer were randomized 1.08:1 between receiving and not receiving a PSMA PET/CT scan before definitive radiotherapy. All other imaging modalities were allowed in the control arm. The primary endpoint was 5-y progression-free survival. Results: Fifty-four men were randomized between November 2020 and December 2021 (PSMA PET/CT, n = 25; control, n = 29). The trial closed early after approval and insurance coverage of PSMA PET/CT. In the PSMA PET/CT arm, 14 patients had localized disease (miT2b-cN0M0), 6 had locally advanced disease (miT3a-bN0M0), 3 had regional metastasis (miN1M0), and 1 had distant metastasis (miM1b). Four patients were upstaged. Conclusion: PSMA PET/CT upstaged 17% of patients, which allowed for more accurate radiotherapy planning. Unfortunately, this trial closed early before completion of target enrollment (54/316, 17%) and was underpowered to assess the effect of PSMA PET/CT on progression-free survival., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting. A national-level reporting system, which provided countries with the option to adopt this new system, was introduced. Regionally, the Epi Info database will be replaced with a DHIS2 regional data platform. This report describes the phased implementation from 2019 to the present. Phase one (2019-2021) involved developing IDSR aggregate and case-based surveillance packages, including pilots in the countries of Mali, Rwanda, and Togo. Phase two (2022) expanded national-level implementation to 27 countries and established the WHO AFRO DHIS2 regional data platform. Phase three (from 2023 to the present) activities have been building local capacity and support for country reporting to the regional platform. By February 2024, eight of 47 AFRO countries had adopted both the aggregate IDSR and case-based surveillance packages, and two had successfully transferred VPD surveillance data to the AFRO regional platform. Challenges included limited human and financial resources, the need to establish data-sharing and governance agreements, technical support for data transfer, and building local capacity to report to the regional platform. Despite these challenges, the transition to DHIS2 will support efficient data transmission to strengthen VPD detection, response, and public health emergencies through improved system integration and interoperability., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The Expanded Programme on Immunization (EPI) and Vaccine Preventable Disease (VPD) Surveillance (VPDS) programs generate multiple data sources (e.g., routine administrative data, VPD case data, and coverage surveys). However, there are challenges with the use of these siloed data for programmatic decision-making, including poor data accessibility and lack of timely analysis, contributing to missed vaccinations, immunity gaps, and, consequently, VPD outbreaks in populations with limited access to immunization and basic healthcare services. Data triangulation, or the integration of multiple data sources, can be used to improve the availability of key indicators for identifying immunization coverage gaps, under-immunized (UI) and un-immunized (zero-dose (ZD)) children, and for assessing program performance at all levels of the healthcare system. Here, we describe the data triangulation processes, prioritization of indicators, and capacity building efforts in Bangladesh, Nigeria, and Rwanda. We also describe the analyses used to generate meaningful data, key indicators used to identify immunization coverage inequities and performance gaps, and key lessons learned. Triangulation processes and lessons learned may be leveraged by other countries, potentially leading to programmatic changes that promote improved access and utilization of vaccination services through the identification of UI and ZD children.

Background: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty., Methods: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups., Results: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint., Conclusion: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19., Methods: Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020., Results: Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, p < 0.01) and increased LOS (B = 0.02, SE = 0.01, p < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, p < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, p < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, p < 0.01, and B = 0.12, SE = 0.05, p < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, p < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, p < 0.001)., Conclusion: Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less ( p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint ( p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R ( p = 0.035) but was linked to lower anxiety in AN-BP ( p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.