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Background: Interventional neuroradiology is a dynamic field with technological advancements constantly driving evolution in clinical practice. Case series provide interventional neuroradiologists the opportunity to describe the clinical implications of novel equipment and techniques almost in real-time, informing broader adoption and directing future research. Complete reporting in case series is vital in enabling readers to detect bias, determine the generalizability of results and replicate study methodology. The aim of this study was to assess the quality of reporting in case series describing endovascular management of vein of Galen malformations., Methods: A systematic search for case series describing endovascular management of vein of Galen malformations in paediatric patients was conducted using a previously published search strategy in Medline, Embase and Web of Science in February 2024. Screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus discussion. Quality of reporting was assessed using adherence to the Preferred Reporting of CasE Series in Surgery (PROCESS) 2020 checklist., Results: We included 19 case series representing a broad range of approaches and endovascular techniques for management of vein of Galen malformations. Overall adherence to the PROCESS 2020 guideline was moderate with a mean of 7.0/13 (54%; range 5.2 - 9.7/13; SD 1.1) items reported. The most consistently reported items related to characteristics of the clinical cohort and details regarding the specific image-guided intervention(s) provided. Items relating to study design, source of funding, pre-intervention patient optimisation, clinical follow-up and potential complications and alternatives for novel techniques/devices were less frequently reported., Conclusions: The quality of reporting in case series describing endovascular management of vein of Galen malformation is suboptimal. Measures to improve the quality of reporting in neurointerventional case series include mandating adherence to reporting guidelines in journal instructions for authors and requiring submission of completed copies of relevant reporting guidelines alongside manuscripts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background:  Free flaps are essential for limb salvage in patients with lower extremity (LE) trauma; however, significant donor-site morbidity could impact functional outcomes. This study compares postoperative ambulatory function between contralateral and ipsilateral free flap harvest in LE traumatic reconstruction., Methods:  A retrospective review was performed on patients who underwent LE reconstruction at a level 1 trauma center from 2009 to 2022. Flap characteristics, injury history, and ambulatory function were collected. Flap harvest laterality was determined in relation to the injured leg. The flaps were categorized as either fasciocutaneous or those that included a muscle component (muscle/myocutaneous). Chi-squared and Mann-Whitney tests were used for statistical analysis., Results:  Upon review, 173 LE free flaps were performed, of which 70 (65.4%) were harvested from the ipsilateral leg and 37 (34.6%) were from the contralateral leg. Among all LE free flaps, the limb salvage rate was 97.2%, and the flap survival rate was 94.4%. Full ambulation was achieved in 37 (52.9%) patients in the ipsilateral cohort and 18 (48.6%) in the contralateral cohort ( p  = 0.679). The average time to full ambulation did not vary between these cohorts ( p  = 0.071). However, upon subanalysis of the 61 muscle/myocutaneous flaps, the ipsilateral cohort had prolonged time to full ambulation (6.4 months, interquartile range [IQR]: 4.8-13.5) compared with the contralateral one (2.3 months, IQR: 2.3 [1.0-3.9]) p  = 0.007. There was no significant difference in time to full ambulation between flap harvest laterality cohorts among the fasciocutaneous flaps ( p  = 0.733)., Conclusion:  Among free flaps harvested from the ipsilateral leg, fasciocutaneous flaps were associated with faster recovery to full ambulation relative to muscle/myocutaneous flaps. Since harvesting muscle or myocutaneous flaps from the ipsilateral leg may be associated with a slower recovery of ambulation, surgeons may consider harvesting from a donor site on the contralateral leg if reconstruction requires a muscle component., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: We descriptively and comparatively evaluated the comprehensiveness of Canadian and US-accredited ophthalmology residency program websites as of August 28, 2024., Methods: Using Canadian Resident Matching Service ( n  = 15) and US Fellowship and Residency Electronic Interactive Database ( n  = 125), we assessed website content across seven criteria: recruitment, faculty, residents, education/research, teaching, benefits, and community. Two independent reviewers used a 40-point system, with Kruskal-Wallis and post-hoc pairwise tests for analysis by country and funding model., Results: US programs more frequently had highly comprehensive websites than Canadian programs (US: 74.4%, Canada: 40%). Canadian programs mostly achieved moderate comprehensiveness (Canada: 60%, US: 22.4%). Larger program size and US origin were significantly linked to higher comprehensiveness scores ( p  < .01)., Conclusion: Our findings suggest that US-based, larger programs offer more extensive online resources. We recommend standardized guidelines to improve residency program website transparency and accessibility for medical learners.

Background: Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes., Methods: We prospectively enrolled 173 ICU patients with sepsis from a suspected respiratory infection (87 without AKI and 86 with AKI on enrollment). Among the AKI patients, 66 were classified as AKI-SP1 and 20 as AKI-SP2 using a three-plasma biomarker classifier. Aptamer-based proteomics assessed 5,212 proteins in urine collected on ICU admission. We compared urinary protein abundances between AKI sub-phenotypes, conducted pathway analyses, tested associations with risk of RRT and blood bacteremia, and predicted AKI-SP2 class membership using LASSO., Measurement and Main Results: In total, 117 urine proteins were higher in AKI-SP2, 195 were higher in AKI-SP1 (FDR < 0.05). Urinary proteins involved in inflammation and chemoattractant of neutrophils and monocytes (CXCL1 and REG3A) and oxidative stress (SOD2) were abundant in AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), proliferation of mesenchymal cells (IL11RA), anti-inflammatory (IL10RB and TREM2) were abundant in AKI-SP1. Pathways related to immune response, complement activation and chemokine signaling were upregulated in AKI-SP2 and pathways of cell adhesion were upregulated in AKI-SP1. Overlap was present between urinary proteins that differentiated AKI sub-phenotypes and proteins that differentiated risk of RRT during hospitalization. Variable correlation was found between top aptamers and ELISA based protein assays. A LASSO derived urinary proteomic model to classify AKI-SP2 had a mean AUC of 0.86 (95% CI: 0.69-0.99)., Conclusion: Our findings suggest AKI-SP1 is characterized by a reparative, regenerative phenotype and AKI-SP2 is characterized as an immune and inflammatory phenotype associated with blood bacteremia. We identified shared biology between AKI sub-phenotypes and eventual risk of RRT highlighting potential therapeutic targets. Urine proteomics may be used to non-invasively classify SP2 participants., Competing Interests: Declarations. Ethics approval and consent to participate: The University of Washington institutional review board approved this study. Consent for publication: No individual personal data is included in the study. The IRB provided waiver of consent to participate in this study. Competing interests: There are no conflicts of interest among the authors of this manuscript., (© 2024. The Author(s).)

The mechanical function of the myocardium is defined by cardiomyocyte contractility and the biomechanics of the extracellular matrix (ECM). Understanding this relationship remains an important unmet challenge due to limitations in existing approaches for engineering myocardial tissue. Here, they established arrays of cardiac microtissues with tunable mechanics and architecture by integrating ECM-mimetic synthetic, fiber matrices, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), enabling real-time contractility readouts, in-depth structural assessment, and tissue-specific computational modeling. They found that the stiffness and alignment of matrix fibers distinctly affect the structural development and contractile function of pure iPSC-CM tissues. Further examination into the impact of fibrous matrix stiffness enabled by computational models and quantitative immunofluorescence implicates cell-ECM interactions in myofibril assembly, myofibril maturation, and notably costamere assembly, which correlates with improved contractile function of tissues. These results highlight how iPSC-CM tissue models with controllable architecture and mechanics can elucidate mechanisms of tissue maturation and disease., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: The semisolid myelin sheath has very fast transverse relaxation and is invisible to conventional MRI sequences. UTE sequences can detect signal from myelin. The major challenge is the concurrent detection of various water components., Methods: The inversion recovery (IR)-based UTE (IR-UTE) sequence employs an adiabatic inversion pulse to invert and suppress water magnetizations. TI plays a key role in water suppression, with negative water magnetizations (negative phase) before the null point and positive water magnetizations (positive phase) after the null point. A series of dual-echo IR-UTE images were acquired with different TIs to detect water phase transition. The effects of TR in phase transition and water suppression were also investigated using a relatively long TR of 500 ms and a short TR of 106 ms. The water phase transition in dual-echo IR-UTE imaging of myelin was investigated in five ex vivo and five in vivo human brains., Results: An apparent phase transition was observed in the second echo at the water signal null point, where the myelin signal was selectively detected by the UTE data acquisition at the optimal TI. The water phase transition point varied significantly across the brain when the long TR of 500 ms was used, whereas the convergence of TIs was observed when the short TR of 106 ms was used., Conclusion: The results suggest that the IR-UTE sequence with a short TR allows uniform inversion and nulling of water magnetizations, thereby providing volumetric imaging of myelin., (© 2024 International Society for Magnetic Resonance in Medicine.)

Compositional changes can occur in the osteochondral junction (OCJ) during the early stages and progressive disease evolution of knee osteoarthritis (OA). However, conventional magnetic resonance imaging (MRI) sequences are not able to image these regions efficiently because of the OCJ region's rapid signal decay. The development of new sequences able to image and quantify OCJ region is therefore highly desirable. We developed a comprehensive ultrashort echo time (UTE) MRI protocol for quantitative assessment of OCJ region in the knee joint, including UTE variable flip angle technique for T 1 mapping, UTE magnetization transfer (UTE-MT) modeling for macromolecular proton fraction (MMF) mapping, UTE adiabatic T 1ρ (UTE-AdiabT 1ρ ) sequence for T 1ρ mapping, and multi-echo UTE sequence for T 2 * mapping. B 1 mapping based on the UTE actual flip angle technique was utilized for B 1 correction in T 1 , MMF, and T 1ρ measurements. Ten normal and one abnormal cadaveric human knee joints were scanned on a 3T clinical MRI scanner to investigate the feasibility of OCJ imaging using the proposed protocol. Volumetric T 1 , MMF, T 1ρ , and T 2 * maps of the OCJ, as well as the superficial and full-thickness cartilage regions, were successfully produced using the quantitative UTE imaging protocol. Significantly lower T 1 , T 1ρ , and T 2 * relaxation times were observed in the OCJ region compared with those observed in both the superficial and full-thickness cartilage regions, whereas MMF showed significantly higher values in the OCJ region. In addition, all four UTE biomarkers showed substantial differences in the OCJ region between normal and abnormal knees. These results indicate that the newly developed 3D quantitative UTE imaging techniques are feasible for T 1 , MMF, T 1ρ , and T 2 * mapping of knee OCJ, representative of a promising approach for the evaluation of compositional changes in early knee OA., (© 2024 John Wiley & Sons Ltd.)

Background: Although optical coherence tomography (OCT) is useful in determining outer retinal architecture, it may be suboptimal when monitoring subtle changes in retinitis pigmentosa (RP) patients. The aim of this study is to investigate precise microperimetric parameters for disease severity identification in RP patients. Methods: A cross-sectional and retrospective study. Thirty-nine eyes of 39 RP patients were included. Associations between logMAR visual acuity (VA), spectral-domain OCT, fundus autofluorescence imaging (FAF), and various microperimetric measures were evaluated. Microperimetric test locations were grouped into "foveal", parafoveal "inner ring", and perifoveal "outer ring". Independent variables were analyzed based on logistic regression, then assessed using area under the receiver operating characteristic curve (AUROC). Results: Among all microperimetric measures, linear regression analysis indicated that mean retinal sensitivity and deep scotoma count at the parafoveal inner ring were the principal parameters associated with decreased VA. The AUROC was highest for deep scotoma count at the inner ring at a value of 0.829, with the cut-off point at 3.5. A visual function index was then established according to the number of parafoveal deep scotoma points, in order of mild (0 points), moderate (1-3 points), and severe (4 or more points). Our microperimetric visual function index also correlated significantly to logMAR VA and previously established FAF patterns. Conclusions: Our study discovered deep scotoma count at the parafoveal inner ring to be a key microperimetric parameter in evaluating vision loss in RP patients. Those with four or more deep scotoma points at the parafoveal inner ring are more likely to have functional low vision.

The batteries that power untethered underwater vehicles (UUVs) serve a single purpose: to provide energy to electronics and motors; the more energy required, the bigger the robot must be to accommodate space for more energy storage. By choosing batteries composed primarily of liquid media [e.g., redox flow batteries (RFBs)], the increased weight can be better distributed for improved capacity with reduced inertial moment. Here, we formed an RFB into the shape of a jellyfish, using two redox chemistries and architectures: (i) a secondary ZnBr 2 battery and (ii) a hybrid primary/secondary ZnI 2 battery. A UUV was able to be powered solely by RFBs with increased volumetric ( Q ~ 11 ampere-hours per liter) and areal (108 milliampere-hours per square centimeter) energy density, resulting in a long operational lifetime ( T ~ 1.5 hours) for UUVs composed of primarily electrochemically energy-dense liquid (~90% of the robot's weight).

The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of Myotis . Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We find that Myotis bats have some of the most significant variation in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived M. lucifugus . We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in Myotis and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms., Competing Interests: Declaration of Interests: The authors declare no competing interests.

Aim: To map the existing evidence and identify research gaps regarding the self-management of prediabetes or type 2 diabetes among first-generation immigrants ≥ 18 years., Design: A scoping review followed the JBI guidelines and was in accordance with the PRISMA extension for Scoping Reviews., Methods: A systematic search of CINAHL, Cochrane, EMBASE, MEDLINE, PsycINFO, ProQuest, SCOPUS and the Web of Science was conducted. Grey literature and reference lists of included studies were searched for additional citations. Articles published in English from the database inception to February 2023 were included., Results: We included 96 studies, of which 28.1% were published within the last 5 years. Most studies (71.9%) were conducted in the United States. Study participants were recruited mainly from community settings and English was their second language. The most common study methodologies used were cross-sectional surveys and phenomenological interviews. Only two studies specifically focussed on individuals with prediabetes. Multiple factors, such as age, gender, country of origin and other societal, linguistic, cultural and resource barriers or facilitators, as well as patient's cultural unique experiences, were of particular significance for self-management behaviours. Although several studies reported that culturally tailored interventions were feasible and acceptable among first-generation immigrants living with type 2 diabetes but not prediabetes, the duration and intensity of these interventions varied., Conclusion: Health professionals should consider various demographic, societal, linguistic and cultural factors, such as participants' low English language proficiency, and provide appropriate support for this group to ensure better self-management behaviours. Tailoring interventions to individual and cultural preferences in collaboration with key stakeholders is crucial for adult immigrants with prediabetes and type 2 diabetes across diverse cultural and ethnic groups., Impact: Developing and applying culturally tailored self-management interventions for the targeted population, particularly those with prediabetes, should be an important direction for future research. No Patient or Public Contribution., (© 2024 John Wiley & Sons Ltd.)

Across cell types and organisms, thousands of RNAs display asymmetric subcellular distributions. The study of this process often requires quantifying abundances of specific RNAs at precise subcellular locations. To analyze subcellular transcriptomes, multiple proximity-based techniques have been developed in which RNAs near a localized bait protein are specifically labeled, facilitating their biotinylation and purification. However, these complex methods are often laborious and require expensive enrichment reagents. To streamline the analysis of localized RNA populations, we developed Oxidation-Induced Nucleotide Conversion sequencing (OINC-seq). In OINC-seq, RNAs near a genetically encoded, localized bait protein are specifically oxidized in a photo-controllable manner. These oxidation events are then directly detected and quantified using high-throughput sequencing and our software package, PIGPEN, without the need for biotin-mediated enrichment. We demonstrate that OINC-seq can induce and quantify RNA oxidation with high specificity in a dose- and light-dependent manner. We further show the spatial specificity of OINC-seq by using it to quantify subcellular transcriptomes associated with the cytoplasm, ER, nucleus, and the inner and outer membranes of mitochondria. Finally, using transgenic zebrafish, we demonstrate that OINC-seq allows proximity-mediated RNA labeling in live animals. In sum, OINC-seq together with PIGPEN provide an accessible workflow for the analysis of localized RNAs across different biological systems., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Glycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of transient chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS. Following expression in T cells, the CAR could be "armed" with recombinant VAR2CSA lectins (rVAR2) to target tumor cells expressing oncofetal CS. While unarmed CAR T cells remained inactive in the presence of target cells, VAR2-armed CAR T cells displayed robust activation and the ability to eliminate diverse tumor cell types in vitro. Cytotoxicity of the CAR T cells was proportional to the concentration of rVAR2 available to the CAR, offering a potential molecular handle to finetune CAR T cell activity. In vivo, armed CAR T cells rapidly targeted bladder tumors and increased the survival of tumor-bearing mice. Thus, our work indicates that cancer-restricted glycosaminoglycans may be exploited as potential targets for CAR T cell therapy., Competing Interests: Disclosure and competing interests statement MD as the corresponding author certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: MD, AS, and PHS are co-founders of, and shareholders in, VAR2 Pharmaceuticals. NAN and TG are consultants for VAR2 Pharmaceuticals. VAR2 Pharmaceuticals is a biotechnology company that specializes in the therapeutic development of the VAR2CSA technology (www.var2pharma.com). The remaining authors declare no competing interests., (© 2024. The Author(s).)

Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl 2 ) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl 2 induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl 2 -induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl 2 -induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Accurate effect estimates are needed to inform input parameters of health economic models. Central-line-associated bloodstream infections (CLABSIs) and catheter-related bloodstream infections (CRBSIs) are different definitions used for central-line bloodstream infections and may represent dissimilar patients, but previous meta-analyses did not differentiate between CLABSIs/CRBSIs., Aim: To determine outcome effect estimates in CLABSI and CRBSI patients, compared to uninfected patients., Methods: PubMed, Embase, and CINAHL were searched from January 2000 to March 2024 for full-text studies reporting all-cause mortality and/or hospital length of stay (LOS) in adult inpatients with and without CLABSI/CRBSI. Two investigators independently reviewed all potentially relevant studies and performed data extraction. Odds ratio for mortality and mean difference in LOS were pooled using random-effects models. Risk of study bias was assessed using ROBINS-E., Findings: Thirty-six studies were included. Sixteen CLABSI and 12 CRBSI studies reported mortality. The mortality odds ratios of CLABSIs and CRBSIs, compared to uninfected patients, were 3.19 (95% CI: 2.44, 4.16; I 2  = 49%) and 2.47 (95% CI: 1.51, 4.02; I 2  = 82%), respectively. Twelve CLABSI and eight CRBSI studies reported hospital LOS; only three CLABSI studies and two CRBSI studies accounted for the time-dependent nature of CLABSIs/CRBSIs. The mean differences in LOS for CLABSIs and CRBSIs compared to uninfected patients were 16.14 days (95% CI: 9.27, 23.01; I 2  = 91%) and 16.26 days (95% CI: 10.19, 22.33; I 2  = 66%), respectively., Conclusion: CLABSIs and CRBSIs increase mortality risk and hospital LOS. Few published studies accounted for the time-dependent nature of CLABSIs/CRBSIs, which can result in overestimation of excess hospital LOS., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: Nordalbergin is a coumarin extracted from Dalbergia sissoo DC. To date, the biological effects of nordalbergin have not been well investigated. To investigate the anti-inflammatory responses and the anti-oxidant abilities of nordalbergin using lipopolysaccharide (LPS)-activated macrophages and LPS-induced sepsis mouse model., Materials and Methods: Production of nitrite oxide (NO), prostaglandin E2 (PGE 2 ), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β), reactive oxygen species (ROS), tissue damage and serum inflammatory markers, and the activation of the NLRP3 inflammasome were examined., Results: Our results indicated that nordalbergin reduced the production of NO and pro-inflammatory cytokines in vitro and ex vivo. Nordalbergin also suppressed iNOS and cyclooxygenase-2 expressions, decreased NF-κB activity, and attenuated MAPKs signaling pathway activation by decreasing JNK and p38 phosphorylation by LPS-activated J774A.1 macrophages. Notably, nordalbergin diminished NLRP3 inflammasome activation via repressing the maturation of IL-1β and caspase-1 and suppressing ROS production by LPS/ATP- and LPS/nigericin-activated J774A.1 macrophages. Furthermore, nordalbergin exhibited protective effects against the infiltration of inflammatory cells and also inhibited the levels of organ damage markers (AST, ALT, BUN) by LPS-challenged mice., Conclusion: Nordalbergin possesses anti-inflammatory effects in macrophage-mediated innate immune responses, alleviates ROS production, decreases NLRP3 activation, and exhibits protective effects against LPS-induced tissue damage in mice., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: This systematic review and meta-analysis aimed to synthesize the evidence and examine the effect of telerehabilitation interventions compared to face-to-face rehabilitation interventions on physical functioning, mental health, and pain reduction among employed individuals, 18 years old and older., Methods: Following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search syntax was created and inputted into Ovid Medline, APA PsycINFO, Ovid Embase, CINAHL, and Scopus. Critical appraisal of the included studies was conducted by two researchers to assess the risk of bias. A meta-analysis was completed for the randomized controlled trials and GRADE was used to determine the certainty of the evidence., Results: A total of 16 out of 4319 articles were included in this review. This systematic review and meta-analysis found no significant differences between telerehabilitation interventions for physical functioning, mental health, and pain reduction outcomes compared to traditional rehabilitation interventions., Conclusion: The study findings indicate that telerehabilitation is less effective than in-person care for occupational therapy and physical therapy services. Future research may look at addressing the limitations of the current study to produce more conclusive results, such as exploring the length of the intervention, knowledge and confidence of intervention application, and follow-ups., Systematic Review Registration: This systematic review has been registered with PROSPERO under registration number CRD42022297849 on April 8th, 2022., (© 2024. The Author(s).)

While tension-type headache (TTH) is the most common primary headache disorder, its effect according to sex, race and ethnicity remains unclear. We investigated disparities in sex, racial and ethnic representation in TTH clinical trials with comparison to global disease burdens. In this cross-sectional analysis, TTH clinical trials had female overrepresentation and racial and ethnic minority underrepresentation, which may affect understanding of the impact of TTH on different populations and personalized treatment development. Trial enrollment that is diverse and reflective of global disease burdens is crucial for improving study generalizability, understanding of diverse clinical presentations, and ensuring healthcare equity.

Background: Hypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease., Methods: Using brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater relative T2 signal intensity suggests gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, fasting triglycerides, and the presence of hypertension (n=449), diabetes mellitus (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Dietary risk factors for gliosis were assessed in a prospective analysis. Statistical testing was performed using linear or logistic regression., Results: Greater MBH/AMY T2 signal ratios were associated with higher BMI (β = 21.5 [95% CI, 15.4-27.6]; P <0.001), higher fasting triglycerides (β = 1.1 [95% CI, 0.6-1.7]; P <0.001), lower HDL-C (β = -20.8 [95% CI, -40.0 to -1.6]; P =0.034), and presence of hypertension (odds ratio, 1.2 [95% CI, 1.1-1.4]; P =0.0088), and the latter two were independent of BMI. Findings for diabetes mellitus were mixed and attenuated by adjusting for BMI. Metabolic syndrome was associated with MBH/AMY T2 signal ratios (odds ratio, 1.3 [95% CI, 1.1-1.6]; P <0.001). Model results were almost uniformly confirmed by the positive control ratios, whereas negative control ratios that did not test the MBH were unrelated to any outcomes (all P ≥0.05). T2 signal ratios were not associated with prevalent coronary heart disease (all P >0.05), but confidence intervals were wide. Self-reported percentages of macronutrient intake were not consistently related to future T2 signal ratios., Conclusions: Using a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, even independent of adiposity. Our results highlight the need to consider neurologic mechanisms to understand and improve cardiometabolic health., Competing Interests: Disclosures EAS has provided consultation to Amgen, Inc. The other authors report no conflicts.

Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can be used to assess microstructural features of skeletal muscle that are related to tissue function. Although widely used, direct correlations between DTI derived metrics such as fractional anisotropy and spatially matched tissue microstructure assessed with histology have not been performed. This study investigated the relationship between scalar-based DTI measurements and histologically derived muscle microstructural measurements in rat rotator cuff muscles. Despite meticulous co-localization of MRI and histology data, negligible correlations were found between DTI metrics and histological measurements including muscle fiber diameter, cross-sectional area, and surface-to-volume ratio. These findings highlight the challenges in validating DTI with histology due to requirements in anatomical co-localization, necessity of high-quality histology, and consideration of diffusion measurement scales. Our findings underscore the need for further research with optimized imaging parameters to enhance our knowledge regarding the sensitivity of DTI to important features of muscle microstructure., Competing Interests: Competing Interests Statement The authors declare no competing interests.

In this study, we describe a comprehensive 3D magnetic resonance imaging (MRI) protocol designed to assess major tissue and fluid components in the brain. The protocol comprises four different sequences: 1) magnetization transfer prepared Cones (MT-Cones) for two-pool MT modeling to quantify macromolecular content; 2) short-TR adiabatic inversion-recovery prepared Cones (STAIR-Cones) for myelin water imaging; 3) proton-density weighted Cones (PDw-Cones) for total water imaging; and 4) highly T 2 weighted Cones (T 2 w-Cones) for free water imaging. By integrating these techniques, we successfully mapped key brain components-namely macromolecules, myelin water, intra/extracellular water, and free water-in ten healthy volunteers and five patients with multiple sclerosis (MS) using a 3T clinical scanner. Brain macromolecular proton fraction (MMPF), myelin water proton fraction (MWPF), intra/extracellular water proton fraction (IEWPF), and free water proton fraction (FWPF) values were generated in white matter (WM), grey matter (GM), and MS lesions. Excellent repeatability of the protocol was demonstrated with high intra-class correlation coefficient (ICC) values. In MS patients, the MMPF and MWPF values of the lesions and normal-appearing WM (NAWM) were significantly lower than those in normal WM (NWM) in healthy volunteers. Moreover, we observed significantly higher FWPF values in MS lesions compared to those in NWM and NAWM regions. This study demonstrates the capability of our technique to volumetrically map major brain components. The technique may have particular value in providing a comprehensive assessment of neuroinflammatory and neurodegenerative diseases of the brain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

RNA molecules are localized to subcellular regions through interactions between localization-regulatory cis-elements and trans-acting RNA binding proteins (RBPs). However, the identities of RNAs whose localization is regulated by a specific RBP as well as the impacts of that RNA localization on cell function have generally remained unknown. Here, we demonstrate that the RBP HNRNPA2B1 acts to keep specific RNAs out of neuronal projections. Using subcellular fractionation, high-throughput sequencing, and single molecule RNA FISH, we find that hundreds of RNAs demonstrate markedly increased abundance in neurites in HNRNPA2B1 knockout cells. These RNAs often encode motor proteins and are enriched for known HNRNPA2B1 binding sites and motifs in their 3' UTRs. The speed and processivity of microtubule-based transport is impaired in these cells, specifically in their neurites. HNRNPA2B1 point mutations that increase its cytoplasmic abundance relative to wildtype lead to stronger suppression of RNA mislocalization defects than seen with wildtype HNRNPA2B1. We further find that the subcellular localizations of HNRNPA2B1 target RNAs are sensitive to perturbations of RNA decay machinery, suggesting that it is HNRNPA2B1's known role in regulating RNA stability that may explain these observations. These findings establish HNRNPA2B1 as a negative regulator of neurite RNA abundance and link the subcellular activities of motor proteins with the subcellular abundance of the RNAs that encode them.

Background: During the COVID-19 pandemic period, it was difficult to carry out regular and scheduled follow-up of patients in the outpatient department, especially during lockdown periods. However, early detection of initial infection or other serious conditions is vital for patients after ocular surgery, such as intravitreal injection (IVI) for age-related macular degeneration (AMD)., Objective: We evaluated the use of a smartphone-based postoperative care chatbot system (PCCS) with an instant bidirectional feedback system for patients to self-report postoperative symptoms and signs., Methods: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patients to report and grade 6 ocular symptoms and signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days post surgery to assess their symptoms and signs each day after receiving an alert. Data were automatically collected using a cloud computer system, including symptom grades and messages sent to medical staff for further medical assistance. A user satisfaction questionnaire was administered to the patients on the seventh day post surgery., Results: In total, 185 patients participated in this study. There were 26 (3.03%) reports of symptom grade deterioration (including increased blurred vision, eye swelling, nausea, and floaters or flashes) from 12 (6.5%) patients. We found no difference in the gender of patients who received an early medical consultation. One case of endophthalmitis was reported, wherein an improvement was observed after prompt administration of IVI antibiotics twice. Overall, 87% (n=185) of patients were satisfied or very satisfied with communicating their symptoms instantly through the app; they were willing to use it again and believed that it could improve the quality of care. Seven of the 185 (3.8%) patients had an earlier medical consultation and 1 (0.5%) had endophthalmitis., Conclusions: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing the quality of care in early medical consultations without gender differences among patients with AMD receiving IVI, and achieved satisfactory responses from patients., (©Pei-Chang Wu, Wei-Yu Chiang, Jung Lo, Jong-Jer Lee, Yung-Jen Chen, Hsi-Kung Kuo, Jie-Shin Chiau, Shu-Hui Hsu, Yi-Hao Chen. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.08.2024.)

Aims: The dentistry program is extremely demanding mentally and physically. Consequently, it can induce high levels of stress, anxiety and depression in students. There is some research in measuring these ramifications on dental students, but they lack the influence of the COVID-19 pandemic which has brought about many fundamental changes to the curriculum of dental students. The aim of this study was to assess dental students' mental health through the Depression, Anxiety and Stress Scale (DASS-21) during the COVID-19 pandemic in an Australian dental School., Methods: The Bachelor of Dental Science (Honours) students enrolled in years 2-5 were requested to complete an online questionnaire that included the DASS-21 and additional questions regarding the impact of COVID-19 on quality of life. Jamovi was utilized to conduct descriptive data analysis., Results: 179 students completed the survey with 81 males (45%) and 98 females (55%). 70.4% of the participants described elevated anxiety for the health of their loved ones and themselves during the COVID-19 pandemic. The overall mean DASS-21 scores were 7.1 (5.07) in depression, 4.9 (4.00) in anxiety and 6.5 (4.32) in stress., Conclusions: The results indicate that the COVID-19 pandemic negatively impacted the mental health of dental students. While further research is still required, it is important for universities to recognize how this pandemic affected the mental wellbeing of students so that they can implement appropriate support programs and improve dental education., Clinical Relevance: The COVID-19 pandemic has had a profound impact on social and mental health worldwide, and dental students are notably affected. Recognized as a psychological risk factor, COVID-19 has been linked to an increased rate of suicidal deaths. This paper underlines the importance of recognizing the full scope of the pandemic's impact on dental students, including their views and the potential effects on their physical and mental health. The study indicates a pressing need for more robust support from the organizations to improve the mental health and overall well-being of dental students., (© 2024 The Author(s). Australian Dental Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Dental Association.)

Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial., Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction., Results: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) ( p-value-for-interaction = 0.03)., Conclusion: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.

Guideline Title: IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections RELEASE DATE: October 2, 2023 PRIOR VERSION: March 16, 2020 DEVELOPER: IWGDF Editorial Board FUNDING SOURCE: International Working Group on the Diabetic Foot (IWGDF), Infectious Diseases Society of America (IDSA) TARGET POPULATION: Adults with suspected or confirmed diabetes-related foot infections., (© 2024 Society of Hospital Medicine.)

Personalized cancer therapeutics bring directed treatment options to patients based on their tumor's genetic signature. Unfortunately, tumor genomes are remarkably adaptable, and acquired resistance through gene mutation frequently occurs. Identifying mutations that promote resistance within drug-treated patient populations can be cost, resource, and time intensive. Accordingly, base editing, enabled by Cas9-deaminase domain fusions, has emerged as a promising approach for rapid, large-scale gene variant screening in situ. Here, we adapt and optimize a conditional activation-induced cytidine deaminase (AID)-dead Cas9 (dCas9) system, which demonstrates greater heterogeneity of edits with an expanded footprint compared to the most commonly utilized cytosine base editor, BE4. In combination with a custom single guide RNA (sgRNA) library, we identify individual and compound variants in epidermal growth factor receptor (EGFR) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that confer resistance to established EGFR inhibitors. This system and analytical pipeline provide a simple, highly scalable platform for cis or trans drug-modifying variant discovery and for uncovering valuable insights into protein structure-function relationships., Competing Interests: Declaration of interests All authors are or were previously full-time employees of Genentech and are shareholders of Roche., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  Historically, the use of intraoperative vasopressors during free flap lower extremity (LE) reconstruction has been proposed to adversely affect flap survival due to concerns about compromising flap perfusion. This study aims to analyze the impact of intraoperative vasopressor use and fluid administration on postoperative outcomes in patients undergoing traumatic LE reconstruction., Methods:  Patients who underwent LE free flap reconstruction between 2015 and 2023 at a Level I Trauma Center were retrospectively reviewed. Statistical analysis was conducted to evaluate the association between vasopressor use and intraoperative fluids with partial/complete flap necrosis, as well as the differential effect of vasopressor use on flap outcomes based on varying fluid levels., Results:  A total of 105 LE flaps were performed over 8 years. Vasopressors were administered intraoperatively to 19 (18.0%) cases. Overall flap survival and limb salvage rates were 97.1 and 93.3%, respectively. Intraoperative vasopressor use decreased the overall risk of postoperative flap necrosis (OR 0.00005, 95% CI [9.11 × 10 -9 -0.285], p  = 0.025), while a lower net fluid balance increased the risk of this outcome (OR 0.9985, 95% CI [0.9975-0.9996], p  = 0.007). Further interaction analysis revealed that vasopressor use increased the risk of flap necrosis in settings with a higher net fluid balance (OR 1.0032, 95% CI [1.0008-1.0056], p -interaction =0.010)., Conclusion:  This study demonstrated that intraoperative vasopressor use and adequate fluid status may be beneficial in improving flap outcomes in LE reconstruction. Vasopressor use with adequate fluid management can optimize hemodynamic stability when necessary during traumatic LE microvascular reconstruction without concern for increased risk of flap ischemia., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts., Methods: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations., Results: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk., Conclusions: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Photoperiod insensitivity (auto-flowering) in drug-type Cannabis sativa circumvents the need for short day (SD) flowering requirements making outdoor cultivation in high latitudes possible. However, the benefits of photoperiod insensitivity are counterbalanced by low cannabinoid content and poor flower quality in auto-flowering genotypes. Despite recent studies in cannabis flowering, a mechanistic understanding of photoperiod insensitivity is still lacking. We used a combination of genome-wide association study and genetic fine-mapping to identify the genetic cause of auto-flowering in cannabis. We then used gene expression analyses and transient transformation assays to characterize flowering time control. Herein, we identify a splice site mutation within circadian clock gene PSEUDO-RESPONSE REGULATOR 37 (CsPRR37) in auto-flowering cannabis. We show that CsPRR37 represses FT expression and its circadian oscillations transition to a less repressive state during SD as compared to long days (LD). We identify several key circadian clock genes whose expression is altered in auto-flowering cannabis, particularly under non-inductive LD. Research into the pervasiveness of this mutation and others affecting flowering time will help elucidate cannabis domestication history and advance cannabis breeding toward a more sustainable outdoor cultivation system., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts., Methods and Results: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72)., Conclusions: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Gender-based violence (GBV) poses a significant concern in the construction and natural resources industries, where women, due to lower social status and integration, are at heightened risk. This systematic review aimed to identify the prevalence and experience of GBV in the construction and natural resources industries. A systematic search across databases including PubMed, OVID, Scopus, Web of Science, and CINAHL was conducted. The Risk of Bias Instrument for Cross-sectional Surveys of Attitudes and Practices by McMaster University and the Critical Appraisal of Qualitative Studies by the Center for Evidence Based Medicine at the University of Oxford were used to assess the studies included in the review. Six articles were included after full-text analysis. GBV was reported in the construction, mining, urban forestry, and arboriculture sectors. Workplace GBV was measured differently across the studies, and all studies examined more than one form of GBV. The main forms of GBV discussed in these studies were discrimination, sexual harassment, and sexism. The studies provided some insight for demographic factors that may or may not be associated with GBV, such as age, region of work, and number of years working in the industry. The review also suggests that workplace GBV has a negative impact on mental health and well-being outcomes, such as higher levels of stress and lower job satisfaction. The current research has not established the effectiveness of interventions, tools, or policies in these workplaces. Thus, additional research should include intervention studies that aim to minimize or prevent GBV in male-dominated workplaces. The current study can bring awareness and acknowledgement towards GBV in the workplace and highlight the importance of addressing it as this review outlines the negative consequences of GBV on mental health and well-being in these male-dominated industries., Competing Interests: Conflict of interest: Behdin Nowrouzi-Kia and Vijay Kumar Chattu are editorial board members for AIMS Public Health and were not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 the Author(s), licensee AIMS Press.)

This submission comprises the proceedings of the 1st Virtual Imaging Trials in Medicine conference, organized by Duke University on April 22-24, 2024. The listed authors serve as the program directors for this conference. The VITM conference is a pioneering summit uniting experts from academia, industry and government in the fields of medical imaging and therapy to explore the transformative potential of in silico virtual trials and digital twins in revolutionizing healthcare. The proceedings are categorized by the respective days of the conference: Monday presentations, Tuesday presentations, Wednesday presentations, followed by the abstracts for the posters presented on Monday and Tuesday.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene., Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations., Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability., Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Purpose: To investigate the feasibility and application of a novel imaging technique, a three-dimensional dual adiabatic inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence, for high contrast assessment of cartilaginous endplate (CEP) imaging with head-to-head comparisons between other UTE imaging techniques., Method: The DIR-UTE sequence employs two narrow-band adiabatic full passage (AFP) pulses to suppress signals from long T 2  water (e.g., nucleus pulposus (NP)) and bone marrow fat (BMF) independently, followed by multispoke UTE acquisition to detect signals from the CEP with short T 2 relaxation times. The DIR-UTE sequence, in addition to three other UTE sequences namely, an IR-prepared and fat-saturated UTE (IR-FS-UTE), a T 1 -weighted and fat-saturated UTE sequence (T 1w -FS-UTE), and a fat-saturated UTE (FS-UTE) was used for MR imaging on a 3 T scanner to image six asymptomatic volunteers, six patients with low back pain, as well as a human cadaveric specimen. The contrast-to-noise ratio of the CEP relative to the adjacent structures-specifically the NP and BMF-was then compared from the acquired images across the different UTE sequences., Results: For asymptomatic volunteers, the DIR-UTE sequence showed significantly higher contrast-to-noise ratio values between the CEP and BMF (CNR CEP-BMF ) (19.9 ± 3.0) and between the CEP and NP (CNR CEP-NP ) (23.1 ± 1.7) compared to IR-FS-UTE (CNR CEP-BMF : 17.3 ± 1.2 and CNR CEP-NP : 19.1 ± 1.8), T 1w -FS-UTE (CNR CEP-BMF : 9.0 ± 2.7 and CNR CEP-NP : 10.4 ± 3.5), and FS-UTE (CNR CEP-BMF : 7.7 ± 2.2 and CNR CEP-NP : 5.8 ± 2.4) for asymptomatic volunteers (all P-values < 0.001). For the spine sample and patients with low back pain, the DIR-UTE technique detected abnormalities such as irregularities and focal defects in the CEP regions., Conclusion: The 3D DIR-UTE sequence is able to provide high-contrast volumetric CEP imaging for human spines on a clinical 3 T scanner., (© 2023. The Author(s).)

Objective: To examine potential health disparities due to a broad reliance on telehealth during the COVID-19 pandemic, the authors studied the impact of video-enabled tablets provided by the U.S. Department of Veterans Affairs (VA) on psychotherapy usage among rural versus urban, Black versus White, and female versus male veterans., Methods: Psychotherapy usage trends before and after onset of the COVID-19 pandemic were examined among veterans with at least one mental health visit in 2019 (63,764 tablet recipients and 1,414,636 nonrecipients). Adjusted difference-in-differences and event study analyses were conducted to compare psychotherapy usage among tablet recipients and nonrecipients (March 15, 2020-December 31, 2021) 10 months before and after tablet issuance. Analyses were stratified by rurality, sex, and race., Results: Adjusted analyses demonstrated that tablet receipt was associated with increases in psychotherapy visit frequency in every patient group studied (rural, 27.4%; urban, 24.6%; women, 30.5%; men, 24.4%; Black, 20.8%; White, 28.1%), compared with visits before tablet receipt. Compared with men, women had statistically significant tablet-associated psychotherapy visit increases (video visits, 1.2 per year; all modalities, 1.0 per year)., Conclusions: VA-issued tablets led to increased psychotherapy usage for all groups examined, with similar increases found for rural versus urban and Black versus White veterans and higher increases for women versus men. Eliminating barriers to Internet access or device ownership may improve mental health care access among underserved or historically disadvantaged populations. VA's tablet program offers insights to inform policy makers' and health systems' efforts to bridge the digital divide., Competing Interests: The authors report no financial relationships with commercial interests.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms., Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group., Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit., Exposure: AHIs., Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling., Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs., Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs)., Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments., Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants., Exposures: AHIs., Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location., Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders., Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Background: Cognitive-motor step training can improve stepping, balance and mobility in people with multiple sclerosis (MS), but effectiveness in preventing falls has not been demonstrated., Objectives: This multisite randomised controlled trial aimed to determine whether 6 months of home-based step exergame training could reduce falls and improve associated risk factors compared with usual care in people with MS., Methods: In total, 461 people with MS aged 22-81 years were randomly allocated to usual care (control) or unsupervised home-based step exergame training (120 minutes/week) for 6 months. The primary outcome was rate of falls over 6 months from randomisation. Secondary outcomes included physical, cognitive and psychosocial function at 6 months and falls over 12 months., Results: Mean (standard deviation ( SD) ) weekly training duration was 70 (51) minutes over 6 months. Fall rates did not differ between intervention and control groups (incidence rates (95% confidence interval (CI)): 2.13 (1.57-2.69) versus 2.24 (1.35-3.13), respectively, incidence rate ratio: 0.96 (95% CI: 0.69-1.34, p = 0.816)). Intervention participants performed faster in tests of choice-stepping reaction time at 6 months. No serious training-related adverse events were reported., Conclusion: The step exergame training programme did not reduce falls among people with MS. However, it significantly improved choice-stepping reaction time which is critical to ambulate safely in daily life environment., 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: Professor S.R.L discloses the following activities that are related to the content of this manuscript: Editor of textbook Falls in Older People, Cambridge United Press; Manager of New Soouth Wales Fall Prevention and Health Ageing Network; Hon Treasurer of Australia New Zealand Falls Prevention Society. All other authors declare that they have no conflicts of interest.

Few studies have examined the effect of informal care receipt on health care utilization and expenditures while accounting for the potentially endogenous relationship between informal and formal care, and none have examined these relationships for U.S. Veterans. With rapidly increasing investments in caregiver supports over the past decade, including stipends for caregivers, the U.S. Department of Veterans Affairs (VA) needs to better understand the costs and benefits of informal care provision. Using a unique data linkage between the 1998-2010 Health and Retirement Study and VA administrative data (n = 2083 Veterans with 9511 person-wave observations), we applied instrumental variable techniques to understand the effect of care from an adult child on Veterans' two-year VA utilization and expenditures. We found that informal care decreased overall utilization by 53 percentage points (p < 0.001) and expenditures by $19,977 (p < 0.01). These reductions can be explained by informal care decreasing the probability of inpatient utilization by 17 percentage points (p < 0.001), outpatient utilization by 57 percentage points (p < 0.001), and institutional long-term care by 3 percentage points (p < 0.05). There were no changes in the probability of non-institutional long-term care use, though these expenditures decreased by $882 (p < 0.05). Expenditure decreases were greatest amongst medically complex patients. Our results indicate relative alignment between VA's stipend payments, which are based on replacement cost methods, and the monetary benefits derived through VA cost avoidances due to informal care. For health systems considering similar caregiver stipend payments, our findings suggest that the cost of these programs may be offset by informal care substituting for formal care, particularly for higher need patients., Competing Interests: Declaration of competing interest Drs. Jacobs, Van Houtven, and Wagner report receiving grant funding from the U.S. Department of Veterans Affairs Health Services Research and Development Service., (Published by Elsevier Ltd.)

Background: Our objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation., Methods: We populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents. We translated candidate biomarkers to a CF cohort via analysis of urine collected prior to, during and two weeks after antibiotics and patients were followed for a median of 3 years after antibiotic use., Results: Polymyxin E treatment resulted in a statistically significant increase in the pro-apoptotic Fas gene relative to control in RNAseq of MPS: fold-change = 1.63, FDR q-value = 7.29 × 10 -5 . Effluent analysis demonstrated an acute rise of soluble Fas (sFas) concentrations that correlated with cellular injury. In 16 patients with CF, urinary sFas concentrations were significantly elevated during antibiotic treatment, regardless of development of AKI. Over a median of three years of follow up, we identified seven cases of incident chronic kidney disease (CKD). Urinary sFas concentrations during antibiotic treatment were significantly associated with subsequent development of incident CKD (unadjusted relative risk = 2.02 per doubling of urinary sFas, 95 % CI = 1.40, 2.90, p < 0.001)., Conclusions: Using an ex-vivo MPS, we identified a novel biomarker of proximal tubule epithelial cell injury, sFas, and translated these findings to a clinical cohort of patients with CF., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest for the research work submitted., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background Mirai, a state-of-the-art deep learning-based algorithm for predicting short-term breast cancer risk, outperforms standard clinical risk models. However, Mirai is a black box, risking overreliance on the algorithm and incorrect diagnoses. Purpose To identify whether bilateral dissimilarity underpins Mirai's reasoning process; create a simplified, intelligible model, AsymMirai, using bilateral dissimilarity; and determine if AsymMirai may approximate Mirai's performance in 1-5-year breast cancer risk prediction. Materials and Methods This retrospective study involved mammograms obtained from patients in the EMory BrEast imaging Dataset, known as EMBED, from January 2013 to December 2020. To approximate 1-5-year breast cancer risk predictions from Mirai, another deep learning-based model, AsymMirai, was built with an interpretable module: local bilateral dissimilarity (localized differences between left and right breast tissue). Pearson correlation coefficients were computed between the risk scores of Mirai and those of AsymMirai. Subgroup analysis was performed in patients for whom AsymMirai's year-over-year reasoning was consistent. AsymMirai and Mirai risk scores were compared using the area under the receiver operating characteristic curve (AUC), and 95% CIs were calculated using the DeLong method. Results Screening mammograms ( n = 210 067) from 81 824 patients (mean age, 59.4 years ± 11.4 [SD]) were included in the study. Deep learning-extracted bilateral dissimilarity produced similar risk scores to those of Mirai (1-year risk prediction, r = 0.6832; 4-5-year prediction, r = 0.6988) and achieved similar performance as Mirai. For AsymMirai, the 1-year breast cancer risk AUC was 0.79 (95% CI: 0.73, 0.85) (Mirai, 0.84; 95% CI: 0.79, 0.89; P = .002), and the 5-year risk AUC was 0.66 (95% CI: 0.63, 0.69) (Mirai, 0.71; 95% CI: 0.68, 0.74; P < .001). In a subgroup of 183 patients for whom AsymMirai repeatedly highlighted the same tissue over time, AsymMirai achieved a 3-year AUC of 0.92 (95% CI: 0.86, 0.97). Conclusion Localized bilateral dissimilarity, an imaging marker for breast cancer risk, approximated the predictive power of Mirai and was a key to Mirai's reasoning. © RSNA, 2024 Supplemental material is available for this article See also the editorial by Freitas in this issue.

Backgrounds/aims: Optimal intravenous fluid management during the perioperative period for patients undergoing pancreaticoduodenectomy (PD) within the framework of enhanced recovery after surgery (ERAS) is unclear. Studies have indicated that excessive total body salt and water can contribute to the development of oedema, leading to increased morbidity and extended hospital stays. This study aimed to assess the effects of an intravenous therapy regimen during postoperative day (POD) 0 to 2 in PD patients within ERAS., Methods: A retrospective interventional cohort study was conducted, and it involved all PD patients before and after implementation of ERAS (2009-2017). In the ERAS group, a targeted maintenance fluid regimen of 20 mL/kg/day with a sodium requirement of 0.5 mmoL/kg/day was administered. Outcome measures included the mmol of sodium and chloride administered, length of stay, and morbidity (postoperative pancreatic fistula, POPF; acute kidney injury, AKI; ileus)., Results: The study included 169 patients, with a mean age of 64 ± 11.3 years. Following implementation of the intravenous fluid therapy protocol, there was a significant reduction in chloride and sodium loading. However, in the multivariable analysis, chloride administered (mmoL/kg) did not independently influence the length of stay; or rates of POPF, ileus, or AKI ( p > 0.05)., Conclusions: The findings suggested that a postoperative intravenous fluid therapy regimen did not significantly impact morbidity. Notably, there was a trend towards reduced length of stay within an increasingly comorbid patient cohort. This targeted fluid regimen appears to be safe for PD patients within the ERAS program. Further prospective research is needed to explore this area.

Objectives  To evaluate the associations between sleep quality and serum levels of neurofilament light (NfL) protein in individuals with premanifest Huntington disease (HD). Materials and Methods  We recruited 28 individuals with premanifest HD from a pre-existing database (of the Huntington's Environmental Research Optimisation Scheme, HEROs). The participants filled out the Pittsburgh Sleep Quality Index (PSQI), a subjective measure of sleep quality, and blood was collected via routine venepuncture to measure peripheral NfL levels. Results  The PSQI scores (median: 5.0; interquartile range: 4.0-7.5) indicated poor sleep quality. General linear modelling revealed no significant ( p  = 0.242) association between PSQI scores and NfL levels. No significant differences were found between individuals with good and poor sleep quality for any demographic variable collected. Discussion  Contrary to studies on other neurological conditions, there was no association between sleep quality and NfL levels in individuals with premanifest HD. This was unexpected, given the influence of environmental factors (such as social network size) on neurodegeneration in individuals with premanifest HD., Competing Interests: Conflicts of Interests The authors have no conflict of interests to declare., (Brazilian Sleep Association. 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/ ).)

Background: Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions., Method: Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison., Results: The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM., Conclusions: The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1021/coif). J.D. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. G.M.B. is a clinical consultant to Magnetica, Brisbane, Australia. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To evaluate efficacy in achieving vaginal delivery with a standardized vaginal compared with oral misoprostol regimen for labor induction at term., Methods: In this single-center, cluster randomized trial, we randomized induction method by week among individuals with gestational age of 37 weeks or more, cervical dilation of 2 cm or less, intact membranes, and indication for delivery to either oral (100 micrograms every 4 hours for up to two doses), or vaginal (25 micrograms every 3 hours for up to five doses) misoprostol regimens, followed by a standardized oxytocin protocol. Individuals with an antepartum stillbirth, major fetal anomalies, malpresentation, ruptured membranes, nonreassuring fetal status, or contraindication to prostaglandin were excluded. The primary outcome was vaginal delivery at first induction attempt. Secondary outcomes included time to delivery, need for oxytocin, chorioamnionitis, and adverse maternal and neonatal outcomes. Outcomes were recorded at the individual level and adjusted for clustering, with analysis by intention to treat., Results: Between May 24, 2021, to September 19, 2022, 1,322 women were randomized to vaginal misoprostol in 33 clusters and 1,224 to oral misoprostol in 37 clusters. Demographic characteristics or initial cervical dilation did not differ between groups. The primary outcome did not differ between induction regimens and occurred in 1,032 (78.1%) of the vaginal misoprostol arm and 945 (77.2%) of the oral misoprostol arm (adjusted relative risk [RR] 1.01, 95% CI, 0.97-1.05). Tachysystole with fetal heart rate changes occurred less frequently with vaginal compared with oral misoprostol (3.5% vs 5.9%, adjusted RR 0.59, 95% CI, 0.40-0.87). Time to delivery did not differ between groups. Oxytocin was less frequently required before delivery in the vaginal misoprostol group (68.8% vs 78.4%, adjusted RR 0.88, 95% CI, 0.84-0.92)., Conclusion: Induction of labor with vaginal compared with oral misoprostol protocols did not increase the frequency of vaginal delivery at term but did reduce the need for oxytocin use before delivery., Clinical Trial Registration: ClinicalTrials.gov, NCT04755218., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the outer retinal bands using OCT in ABCA4- and PRPH2-associated retinopathy and develop a novel imaging biomarker to differentiate between these 2 genotypes., Design: Multicenter case-control study., Participants: Patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-associated retinopathy and an age-matched control group., Methods: Macular OCT was used to measure the thickness of the outer retinal bands 2 and 4 by 2 independent examiners at 4 retinal loci., Main Outcome Measures: Outcome measures included the thicknesses of band 2, band 4, and the band 2/band 4 ratio. Linear mixed modeling was used to make comparisons across the 3 groups. Receiver operating characteristic (ROC) analysis determined the optimal cutoff for the band 2/band 4 ratio to distinguish PRPH2- from ABCA4-associated retinopathy., Results: We included 45 patients with ABCA4 variants, 45 patients with PRPH2 variants, and 45 healthy controls. Band 2 was significantly thicker in patients with PRPH2 compared with ABCA4 (21.4 vs. 15.9 μm, P < 0.001) variants, whereas band 4 was thicker in patients with ABCA4 variants than those with PRPH2 variants (27.5 vs. 21.7 μm, P < 0.001). Similarly, the band 2/band 4 ratio was significantly different (1.0 vs. 0.6 for PRPH2 vs. ABCA4, P < 0.001). The area under the ROC curve was 0.87 for either band 2 (> 18.58 μm) or band 4 (< 26.17 μm) alone and 0.99 (95% confidence interval: 0.97-0.99) for the band 2/band 4 ratio with a cutoff threshold of 0.79, providing 100% specificity., Conclusions: We report an altered outer retinal band profile whereby the band 2/band 4 ratio was able to discriminate between PRPH2- and ABCA4-associated retinopathy. This may have future clinic utility in predicting the genotype and provide further insight into the anatomic correlate of band 2., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP., Methods: We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model., Results: A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I 2 =0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I 2 =0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia., Conclusions: The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)