Principles, functions, and biological implications of m6A in plants.

Over the past decade, N 6-methyladenosine (m6A) has emerged as a prevalent and dynamically regulated modification across the transcriptome; it has been reversibly installed, removed, and interpreted by specific binding proteins, and has played crucial roles in molecular and biological processes. Within this scope, we consolidate recent advancements of m6A research in plants regarding gene expression regulation, diverse physiologic and pathogenic processes, as well as crop trial implications, to guide discussions on challenges associated with and leveraging epitranscriptome editing for crop improvement.

Associations of Urban Blue and Green Spaces With Coronary Artery Calcification in Black Individuals and Disadvantaged Neighborhoods.

BACKGROUND: Proximity to urban blue and green spaces has been associated with improved cardiovascular health; however, few studies have examined the role of race and socioeconomic status in these associations. METHODS: Data were from the CARDIA study (Coronary Artery Risk Development in Young Adults). We included longitudinal measurements (1985-1986 to 2010-2011) of blue and green spaces, including percentage of blue space cover, distance to the nearest river, green space cover, and distance to the nearest major park. Presence of coronary artery calcification (CAC) was measured with noncontrast cardiac computed tomography in 2010 to 2011. The associations of blue and green spaces with CAC were assessed with generalized estimating equation regression with adjustment for demographics, individual and neighborhood socioeconomic status, health-related behaviors, and other health conditions. We conducted stratified analyses by race and neighborhood deprivation score to investigate whether the association varied according to social determinants of health. RESULTS: The analytic sample included 1365 Black and 1555 White participants with a mean±SD age of 50.1±3.6 years. Among Black participants, shorter distance to a river and greater green space cover were associated with lower odds of CAC (per interquartile range decrease [1.45 km] to the river: odds ratio [OR], 0.90 [95% CI, 0.84-0.96]; per 10 percentage-point increase of green space cover: OR, 0.85 [95% CI, 0.75-0.95]). Among participants in deprived neighborhoods, greater green space cover was associated with lower odds of CAC (per a 10 percentage-point increase: OR, 0.89 [95% CI, 0.80-0.99]), whereas shorter distance to the park was associated with higher odds of CAC (per an interquartile range decrease [5.3 km]: OR, 1.07 [95% CI, 1.00-1.15]). Black participants in deprived neighborhoods had lower odds of CAC with shorter distance to a river (per an interquartile range decrease: OR, 0.90 [95% CI, 0.82-0.98]) and greater green space cover (per a 10 percentage-point increase: OR, 0.85 [95% CI, 0.75-0.97]). There was no statistical interaction between the blue and green spaces and race or neighborhood characteristics in association with CAC. CONCLUSIONS: Longitudinally, shorter distance to a river and greater green space cover were associated with less CAC among Black participants and those in deprived neighborhoods. Shorter distance to a park was associated with increased odds of CAC among participants in deprived neighborhoods. Black participants residing in more deprived neighborhoods showed lower odds of CAC in association with greater exposure to river and green space cover.

Advancing Wearable Biosensors for Congenital Heart Disease: Patient and Clinician Perspectives: A Science Advisory From the American Heart Association.

Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations. This science advisory reviews the use of wearables in patients with congenital heart disease, how to improve these technologies for clinicians and patients, and ethical and regulatory considerations. Challenges related to the use of wearables are common to every clinical setting, but specific topics for consideration in congenital heart disease are highlighted.

Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.

Comparative transcriptomic profiles of Paulownia catalpifolia under different degrees of chilling stress during the seedling stage.

BACKGROUND: Paulownia, an ecologically and economically valuable plant species native to China, is notable for its excellent timber quality and strong adaptability. Among them, Paulownia catalpifolia displays the ability to survive in cold climate, a trait associated with northern China. Yet, the molecular information for its cold-tolerance has not been explored. This study was to investigate the changes in physiological indices and transcript levels of P. catalpifolia following cold exposure, which could provide evidence for revealing whether there were differences in the genetic basis of inducing physiological perturbations between moderate low temperature (MLT) and extreme low temperature (ELT). RESULTS: The detection of physiological indices under diverse degrees of chilling stress showed similar patterns of alteration. Enhanced accumulation of osmoregulatory substances, such as soluble sugar and soluble protein, were more conducive under ELT compared to MLT in P. catalpifolia. Moreover, we observed leaf wilting symptoms distinctly after exposure to ELT for 48 h, while this effect was not obvious after MLT exposure for 48 h. Comparative transcriptomic analysis between MLT and ELT demonstrated 13,688 differentially expressed genes (DEGs), most of them appeared after 12 h and 48 h of treatment. GO and KEGG analyses elucidated prominent enrichment in aromatic-L-amino-acid decarboxylase activity term and carbohydrate metabolism pathways. Therefore, it was speculated that the DEGs involved in the above processes might be related to the difference in the contents of soluble protein and soluble sugar between MLT and ELT. Time series clustering analyses further highlighted several key genes engaged in the 'Glycosyltransferases', 'Galactose metabolism' and 'Starch and sucrose metabolism' pathways as well as the 'tyrosine decarboxylase activity' term. For instance, cellulose synthase-like A (CLSA2/9), raffinose synthase (RafS2), ß-amylase (BAM1) and tyrosine/DOPA decarboxylase (TYDC1/2/5) genes, diverging in their expression trends between MLT and ELT, might significantly affect the soluble sugar and soluble protein abundance within P. catalpifolia. CONCLUSION: Between MLT and ELT treatments, partial overlaps in response pathways of P. catalpifolia were identified, while several genes regulating the accumulation of osmotic adjustment substances had disparate expression patterns. These findings could provide a novel physiological and molecular perspective for P. catalpifolia to adapt to complex low temperature habitats.

Physiologic Pacing for the Prevention and Treatment of Heart Failure A State-of-the-Art Review.

Permanent pacing from the right ventricular apex can reduce quality of life and increase the risk of heart failure and death. This review summarizes the milestones in the evolution of pacemakers towards "physiologic pacing" with biventricular pacing systems and lead implantation into the cardiac conduction system to synchronize cardiac contraction and relaxation. Both approaches aim to reproduce normal cardiac activation and help prevent and treat heart failure. This review introduces the basic concepts and clinical evidence and discusses practical uses of physiological pacing.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI.

BACKGROUND: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). METHODS: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. DISCUSSION: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02613988.

Increased Interferon Signaling in Vaginal Tissue of Patients With Primary Sjögren Syndrome.

OBJECTIVE: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS. METHODS: Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs]). RESULTS: The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway (P < 0.01). Pathway scores for Janus kinase and signal transducer and activator of transcription (JAK-STAT) and Notch signaling were also higher (P < 0.01 for both pathways). Conversely, transforming growth factor-ß signaling and angiogenesis pathway scores were lower in pSS (P = 0.02 and P = 0.04, respectively). Differences in IFN signaling between patients with pSS and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. IFN-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity. CONCLUSION: Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness).

Intracranial arterial calcification in patients with unruptured and ruptured intracranial aneurysms.

OBJECTIVES: Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). MATERIALS AND METHODS: We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. RESULTS: Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). CONCLUSIONS: Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. CLINICAL RELEVANCE STATEMENT: Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. KEY POINTS: Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

ApoA-I Nanotherapy Rescues Postischemic Vascular Maladaptation by Modulating Endothelial Cell and Macrophage Phenotypes in Type 2 Diabetic Mice.

BACKGROUND: Diabetes is a major risk factor for peripheral arterial disease. Clinical and preclinical studies suggest an impaired collateral remodeling and angiogenesis in response to atherosclerotic arterial occlusion in diabetic conditions, although the underlying mechanisms are poorly understood. OBJECTIVE: To clarify the cellular and molecular mechanisms underlying impaired postischemic adaptive vascular responses and to evaluate rHDL (reconstituted HDL)-ApoA-I nanotherapy to rescue the defect in type 2 diabetic mouse model of hindlimb ischemia. METHODS AND RESULTS: Hindlimb ischemia was induced by unilateral femoral artery ligation. Collateral and capillary parameters together with blood flow recovery were analyzed from normoxic adductor and ischemic gastrocnemius muscles, respectively, at day 3 and 7 post-ligation. In response to femoral artery ligation, collateral lumen area was significantly reduced in normoxic adductor muscles. Distally, ischemic gastrocnemius muscles displayed impaired perfusion recovery and angiogenesis paralleled with persistent inflammation. Muscle-specific mRNA sequencing revealed differential expression of genes critical for smooth muscle proliferation and sprouting angiogenesis in normoxic adductor and ischemic gastrocnemius, respectively, at day 7 post-ligation. Genes typical for macrophage (Mϕ) subsets were differentially expressed across both muscle types. Cell-specific gene expression, flow cytometry, and immunohistochemistry revealed persistent IFN-I response gene upregulation in arterial endothelial cells, ECs and Mϕs from T2DM mice associated with impaired collateral remodeling, angiogenesis and perfusion recovery. Furthermore, rHDL nanotherapy rescued impaired collateral remodeling and angiogenesis through dampening EC and Mϕ inflammation in T2DM mice. CONCLUSIONS: Our results suggest that an impaired collateral remodeling and sprouting angiogenesis in T2DM mice is associated with persistent IFN-I response in ECs and Mϕs. Dampening persistent inflammation and skewing ECs and Mϕ phenotype toward less inflammatory ones using rHDL nanotherapy may serve as a potential therapeutic target for T2DM peripheral arterial disease.

Cerebral physiologic insult burden in acute traumatic neural injury: a Canadian High Resolution-TBI (CAHR-TBI) descriptive analysis.

BACKGROUND: Over the recent decades, continuous multi-modal monitoring of cerebral physiology has gained increasing interest for its potential to help minimize secondary brain injury following moderate-to-severe acute traumatic neural injury (also termed traumatic brain injury; TBI). Despite this heightened interest, there has yet to be a comprehensive evaluation of the effects of derangements in multimodal cerebral physiology on global cerebral physiologic insult burden. In this study, we offer a multi-center descriptive analysis of the associations between deranged cerebral physiology and cerebral physiologic insult burden. METHODS: Using data from the Canadian High-Resolution TBI (CAHR-TBI) Research Collaborative, a total of 369 complete patient datasets were acquired for the purposes of this study. For various cerebral physiologic metrics, patients were trichotomized into low, intermediate, and high cohorts based on mean values. Jonckheere-Terpstra testing was then used to assess for directional relationships between these cerebral physiologic metrics and various measures of cerebral physiologic insult burden. Contour plots were then created to illustrate the impact of preserved vs impaired cerebrovascular reactivity on these relationships. RESULTS: It was found that elevated intracranial pressure (ICP) was associated with more time spent with cerebral perfusion pressure (CPP) < 60 mmHg and more time with impaired cerebrovascular reactivity. Low CPP was associated with more time spent with ICP > 20 or 22 mmHg and more time spent with impaired cerebrovascular reactivity. Elevated cerebrovascular reactivity indices were associated with more time spent with CPP < 60 mmHg as well as ICP > 20 or 22 mmHg. Low brain tissue oxygenation (PbtO2) only demonstrated a significant association with more time spent with CPP < 60 mmHg. Low regional oxygen saturation (rSO2) failed to produce a statistically significant association with any particular measure of cerebral physiologic insult burden. CONCLUSIONS: Mean ICP, CPP and, cerebrovascular reactivity values demonstrate statistically significant associations with global cerebral physiologic insult burden; however, it is uncertain whether measures of oxygen delivery provide any significant insight into such insult burden.

Stylet-driven leads compared with lumenless leads for left bundle branch area pacing: a systematic review and meta-analysis.

OBJECTIVE: Left bundle branch area pacing (LBBAP) is a novel physiological pacing method for treating left ventricular dyssynchrony. LBBAP is often delivered using lumenless leads (LLL). However, recent studies have also reported the use of style-driven leads (SDL). This study is the first systematic review comparing the outcomes of LBBAP with SDL vs. LLL. METHODS: The review and meta-analysis included all available comparative studies published on Embase, PubMed, Web of Science, CENTRAL, and Scopus up to 6th March 2024. RESULTS: Eight observational studies were included in the review. Meta-analysis showed that success rates of LBBAP performed with LLL and SDL were comparable (OR: 1.72 95% CI: 0.94, 3.17 I2 = 38%). Duration of implantation and total procedural duration were significantly lower in LBBAP performed with SDL. The pacing threshold was significantly higher, while pacing impedance was significantly lower in the SDL compared to the LLL group. Pacing QRS interval, R-wave amplitude, and stimulus to peak left ventricular activation time were similar in the two groups. Intra-operative and post-operative dislodgement were significantly higher in the SDL group, but no difference was noted in intra-operative perforation and pneumothorax risk. CONCLUSION: Limited evidence from observational studies with inherent selection bias shows that success rates for LBBAP may not differ between SDL and LLL. While implantation of SDL may be significantly faster, it carries a higher risk of lead dislodgement. Both SDL and LLL are associated with comparable pacing characteristics except for reduced pacing impedance with SDL.

Single operator experience, learning curve, outcomes, and insights gained with conduction system pacing.

BACKGROUND: Conduction system pacing (CSP) is increasingly utilized to prevent and correct dyssynchrony. Barriers to CSP adoption include limited training, methodologic variability, laboratory slot allocation, and few data on learning curves. We report learning curves/clinical outcomes from a single experienced electrophysiologist who was new to CSP, and share gained insights. METHODS: Retrospective analysis of all patients who underwent attempted CSP implantation (2016-2023). Patient characteristics, ECGs, echocardiograms, fluoroscopy/procedure times, lead data were recorded at implant and follow-up. RESULTS: CSP leads were implanted successfully in 167/191(87.4%) patients with a follow-up of 278 ± 378 days. His-bundle pacing (HBP = 59) and left-bundle-area pacing (LBAP = 108) had similar procedure/fluoroscopy times, QRS duration decreases, and ejection fraction improvements (all p > NS). Eight HBP lead revisions were required for high capture thresholds LBAP demonstrated lower pacing thresholds, higher lead impedances, and greater R-wave amplitudes at implant and follow-up. After 25 HBP cases, implant pacing thresholds, fluoroscopy, procedural times did not decrease. After 25 LBAP cases, there were significant decreases in all these parameters (p < 0.05). A separate analysis in LBAP patients with recorded Purkinje signals showed no differences in paced ECG characteristics between patients with pre- QRS Purkinje signals versus patients with Purkinje signals post-QRS onset. CONCLUSIONS: Experienced implanters who are new to CSP can achieve steady-state procedural/fluoroscopy times after a learning curve of 25 implants. LBAP showed lower capture thresholds and higher success rates. Adequate depth of lead deployment (as determined by published parameters) does not require Purkinje potential to be pre-QRS. Operators new to CSP.can forego HBP and directly implement LBAP.

Testing a Conceptual Model of Physiologic Reserve, Intrinsic Capacity, and Physical Resilience in Hospitalized Older Patients: A Structural Equation Modelling.

INTRODUCTION: The relationship among physiologic reserve, intrinsic capacity, and physical resilience has not been examined, and a conceptual model that includes these key determinants of healthy ageing is needed. This study aimed to test a conceptual model using real-world data to determine the relationships among physiologic reserve, intrinsic capacity, physical resilience, and clinical outcomes. METHODS: This longitudinal study was conducted at a 1,343-bed tertiary-care medical centre. Patients were eligible for inclusion if they were 65 years of age or older and able to communicate independently. Demographic factors, cumulative illness rating scale for geriatrics [CIRS-G] (assessing physiologic reserve), intrinsic capacity, physical resilience instrument for older adults [PRIFOR] (assessing physical resilience), and clinical frailty scale [CFS] were collected at admission. The CFS and EuroQoL 5-dimension 3-level questionnaire [EQ5D] were administered at discharge. RESULTS: The mean age of the 413 patients was 76.34 ± 6.72 (52.5% female). Two conceptual models were identified and supported. Specifically, the path coefficients in the two models showed that the CIRS-G had diverse associations with each intrinsic capacity domain, and that all intrinsic capacity domains (except vitality) were significantly associated with PRIFOR. Moreover, PRIFOR was significantly associated with follow-up CFS, baseline control, and EQ5D scores. CONCLUSION: Physiologic reserve positively correlated with the cognitive and locomotive domains of intrinsic capacity. Moreover, older patients with better intrinsic capacity may have improved physical resilience, which may lead to better clinical outcomes. Efforts to improve the intrinsic capacity and physical resilience of older patients are necessary to promote healthy ageing.

Risk Factors for Falls Among Hospitalized Medical Patients - A Systematic Review and Meta-analysis.

OBJECTIVE: To identify and quantify risk factors for in-hospital falls in medical patients. DATA SOURCES: Six databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) were systematically screened until April 11, 2023, to identify relevant articles. STUDY SELECTION: All titles and abstracts of the retrieved articles were independently screened by 2 researchers who also read the full texts of the remaining articles. Quantitative studies that assessed risk factors for falls among adult patients acutely hospitalized were included in the review. Publications that did not capture internal medicine patients or focused on other specific populations were excluded. DATA EXTRACTION: Information on study characteristics and potential risk factors were systematically extracted. Risk of bias was assessed using the Quality in Prognosis Studies tool. Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology guidelines were followed for reporting. DATA SYNTHESIS: The main outcome was any in-hospital falls. Using a random-effects meta-analysis model, association measures for each risk factor reported in 5 or more studies were pooled. Separate analyses according to effect measure and studies adjusted for sex and age at least were performed. Of 5067 records retrieved, 119 original publications from 25 countries were included. In conclusion, 23 potential risk factors were meta-analyzed. Strong evidence with large effect sizes was found for a history of falls (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.63-3.96; I2, 91%), antidepressants (pooled OR, 2.25; 95% CI, 1.92-2.65; I2, 0%), benzodiazepines (OR, 1.97; 95% CI, 1.68-2.31; I2, 0%), hypnotics-sedatives (OR, 1.90; 95% CI, 1.53-2.36; I2, 46%), and antipsychotics (OR, 1.61; 95% CI, 1.33-1.95; I2, 0%). Furthermore, evidence of associations with male sex (OR, 1.22, 95% CI, 0.99-1.50; I2, 65%) and age (OR, 1.17, 95% CI, 1.02-1.35; I2, 72%) were found, but effect sizes were small. CONCLUSIONS: The comprehensive list of risk factors, which specifies the strength of evidence and effect sizes, could assist in the prioritization of preventive measures and interventions.

Maternal and Neonatal Consequences of Early Augmentation of Labor Among Women With Spontaneous Onset of Labor: A National Population-Based Study.

BACKGROUND: While some labor interventions are essential in preventing maternal and neonatal morbidity, there is little evidence to support systematic early augmentation of labor (EAL). Our objective was to assess the association between EAL and cesarean delivery rate, postpartum hemorrhage and adverse neonatal outcomes. METHODS: Population-based study using data from the 2016 French Perinatal Survey. Women with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. "EAL" was defined by artificial rupture of the membranes (AROM) and/or oxytocin within 1 h of admission and/or duration between interventions of less than 1 h. Women without EAL were women without labor augmentation or without EAL. The primary endpoint, cesarean delivery and the secondary endpoints were compared between women with and without EAL using univariate analysis. A multivariable logistic regression was adjusted on the suspected confounders and a propensity score approach was then performed. RESULTS: Among the 7196 women included, 1524 (21.2%) had EAL. Cesarean delivery rates were significantly higher in the EAL group compared with the no EAL group, 8.40% versus 6.15% (p < 0.01). EAL was associated with cesarean delivery in the multivariable analysis aOR 1.45 95% CI [1.15-1.82] and in the cohort matched on the propensity score, OR 1.56 [1.17-2.07]. EAL was not associated with severe postpartum hemorrhage, low 5-min Apgar score, low neonatal cord pH or transfer to NICU. CONCLUSION: EAL is frequent, involving one in five spontaneous laboring women in France. This practice is associated with an increased cesarean delivery risk.

The Fontan Circulation in Pregnancy: Hemodynamic Challenges and Anesthetic Considerations.

Pregnancy in patients with Fontan physiology presents unique challenges due to altered cardiovascular dynamics inherent to both conditions. The Fontan procedure reroutes venous blood directly to the pulmonary arteries, bypassing the heart, and necessitating precise regulation of pulmonary venous resistance and systemic venous pressure to maintain effective cardiac output. The significant cardiovascular adaptations required during pregnancy to meet the metabolic demands of the mother and fetus can overburden the limited preload capacity and venous compliance in Fontan patients, predisposing them to a spectrum of potential complications, including arrhythmias, heart failure, thromboembolism, and obstetric and fetal risks. This review delineates the essential physiological adaptations during pregnancy and the challenges faced by Fontan patients, advocating for a comprehensive care approach involving multidisciplinary collaboration, vigilant monitoring, tailored anesthetic management, and postpartum care. Understanding the complex dynamics between Fontan physiology and pregnancy is crucial for anesthesiologists to develop and execute individualized management strategies to minimize risks and optimize outcomes for this high-risk population.

Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology.

BACKGROUND: Throughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density. AIMS: To assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology. METHODS: Prospective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11-13 and 36-38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy. RESULTS: Over a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of - 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck. CONCLUSIONS: Our study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

Comparison Between Ultrasonography and Radiography in the Detection of Epiphyseal Ossification Centers of the Knee in Infants With Permanent Congenital Hypothyroidism.

OBJECTIVE: To demonstrate the usefulness of ultrasonography in detecting knee ossification centers in infants with permanent congenital hypothyroidism (PCH). METHODS: From 2011 to 2021, all infants with PCH referred for thyroid ultrasound also underwent left knee ultrasound and radiography on the same day. Knee radiographs were compared with knee sonograms. Two pediatric radiologists reviewed the consensus knee radiographs and sonograms to identify femoral and tibial epiphyseal ossification centers (presence/absence). The concordance between ultrasonography and radiography was assessed. Another radiologist conducted a second late review to evaluate interobserver agreement. RESULTS: We identified 125 patients (65 girls, 60 boys) with a mean age of 24 days (5 days-5 months). On scintigraphy, the thyroid was in place in 66.4%, ectopic in 24%, and absent in 9.6% of patients. The femoral center was observed in 108 patients (86.4%) via sonography and 106 patients (84.8%) via radiography. The tibial center was observed in 84 patients (67.2%) via sonography and radiography. Both femoral and tibial centers were present on sonography and radiography in 84 patients (67.2%). A single nucleus was present in 24 patients (19.2%) on sonography and 22 patients (17.6%) on radiography; it corresponded to the femoral center in all patients. The concordance between ultrasonography and radiography was 99% and 100%, respectively, for the detection of the femoral and tibial centers. Interobserver agreement was substantial to almost perfect for both ultrasonography and radiography. CONCLUSION: Ultrasonography is as effective as radiography in detecting knee ossification centers in PCH. It can be performed at the same time as thyroid examination, in place of radiography.