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Background & Aims: Guidelines recommend use of risk stratification scores for patients presenting with gastrointestinal bleeding (GIB) to identify very-low-risk patients eligible for discharge from emergency departments. Machine learning models may outperform existing scores and can be integrated within the electronic health record (EHR) to provide real-time risk assessment without manual data entry. We present the first EHR-based machine learning model for GIB., Methods: The training cohort comprised 2546 patients and internal validation of 850 patients presenting with overt GIB (ie, hematemesis, melena, and hematochezia) to emergency departments of 2 hospitals from 2014 to 2019. External validation was performed on 926 patients presenting to a different hospital with the same EHR from 2014 to 2019. The primary outcome was a composite of red blood cell transfusion, hemostatic intervention (ie, endoscopic, interventional radiologic, or surgical), and 30-day all-cause mortality. We used structured data fields in the EHR, available within 4 hours of presentation, and compared the performance of machine learning models with current guideline-recommended risk scores, Glasgow-Blatchford Score, and Oakland Score. Primary analysis was area under the receiver operating characteristic curve. Secondary analysis was specificity at 99% sensitivity to assess the proportion of patients correctly identified as very low risk., Results: The machine learning model outperformed the Glasgow-Blatchford Score (area under the receiver operating characteristic curve, 0.92 vs 0.89; P < .001) and Oakland Score (area under the receiver operating characteristic curve, 0.92 vs 0.89; P < .001). At the very-low-risk threshold of 99% sensitivity, the machine learning model identified more very-low-risk patients: 37.9% vs 18.5% for Glasgow-Blatchford Score and 11.7% for Oakland Score (P < .001 for both comparisons)., Conclusions: An EHR-based machine learning model performs better than currently recommended clinical risk scores and identifies more very-low-risk patients eligible for discharge from the emergency department., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Territorial spatial planning could achieve the integration of various plans, resulting in a unified "multi-plan integration" map. Such planning emphasizes the efficient use of territorial spatial patterns and structures to ensure functional perfection, and serves as the spatial framework for building a modern socialist country, particularly in the areas of ecological security and ecological civilization. The past few decades have seen rapid advances in the development of landscape ecology in China. The core concept of "pattern-process-function" has gained significant progress and been widely applied in the initial phase of territorial spatial planning at various levels. We outlined the advancements in the territorial spatial planning system and the core research theories and technologies in landscape ecology. We discussed the progress and shortcomings of key theories and methods of landscape ecology in practical applications of territorial spatial planning, such as ecological security patterns, pattern and process, and scale effects. We proposed the future application of landscape ecology theories and technologies in territorial spatial planning, including overall ecological effects, scale effects, and regional ecological network optimization. Future developments in landscape ecology, especially research on the "human-place-ecology" coupling based on the latest Big Data and AI technology for sustainable development, will provide robust theoretical and methodological supports for the scientific formulation of territorial spatial planning in China.

Background & Aims: Early identification and accurate characterization of overt gastrointestinal bleeding (GIB) enables opportunities to optimize patient management and ensures appropriately risk-adjusted coding for claims-based quality measures and reimbursement. Recent advancements in generative artificial intelligence, particularly large language models (LLMs), create opportunities to support accurate identification of clinical conditions. In this study, we present the first LLM-based pipeline for identification of overt GIB in the electronic health record (EHR). We demonstrate 2 clinically relevant applications: the automated detection of recurrent bleeding and appropriate reimbursement coding for patients with GIB., Methods: Development of the LLM-based pipeline was performed on 17,712 nursing notes from 1108 patients who were hospitalized with acute GIB and underwent endoscopy in the hospital from 2014 to 2023. The pipeline was used to train an EHR-based machine learning model for detection of recurrent bleeding on 546 patients presenting to 2 hospitals and externally validated on 562 patients presenting to 4 different hospitals. The pipeline was used to develop an algorithm for appropriate reimbursement coding on 7956 patients who underwent endoscopy in the hospital from 2019 to 2023., Results: The LLM-based pipeline accurately detected melena (positive predictive value, 0.972; sensitivity, 0.900), hematochezia (positive predictive value, 0.900; sensitivity, 0.908), and hematemesis (positive predictive value, 0.859; sensitivity, 0.932). The EHR-based machine learning model identified recurrent bleeding with area under the curve of 0.986, sensitivity of 98.4%, and specificity of 97.5%. The reimbursement coding algorithm resulted in an average per-patient reimbursement increase of $1299 to $3247 with a total difference of $697,460 to $1,743,649., Conclusions: An LLM-based pipeline can robustly detect overt GIB in the EHR with clinically relevant applications in detection of recurrent bleeding and appropriate reimbursement coding., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the development of antibodies against factor VIII. AHA has previously been reported in association with malignancy and autoimmune disorders, but rarely with liver disease. A prolonged activated partial thromboplastin time is the initial laboratory manifestation of this condition but may be challenging to interpret in the setting of abnormal markers of coagulation typically seen in cirrhosis. We present a case of AHA in a patient with decompensated cirrhosis resulting in refractory bleeding and highlight the complexities of interpreting abnormal coagulation factors in patients with cirrhosis., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Melon ( Cucumis melo L.) is a horticultural crop that is planted globally. Cucumis melo L. cv. Baogua is a typical melon that is suitable for studying fruit development because of its ability to adapt to different climatic conditions. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nucleotides, which play important roles in a wide range of biological processes by regulating gene expression. In this study, the transcriptome of the Baogua melon was sequenced at three stages of the process of fruit development (14 days, 21 days, and 28 days) to study the role of lncRNAs in fruit development. The cis and trans lncRNAs were subsequently predicted and identified to determine their target genes. Notably, 1716 high-confidence lncRNAs were obtained in the three groups. A subsequent differential expression analysis of the lncRNAs between the three groups revealed 388 differentially expressed lncRNAs. A total of 11 genes were analyzed further to validate the transcriptome sequencing results. Interestingly, the MELO3C001376.2 and MSTRG.571.2 genes were found to be significantly ( P  < 0.05) downregulated in the fruits. This study provides a basis to better understand the functions and regulatory mechanisms of lncRNAs during the development of melon fruit., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Maternal depression during pregnancy is prevalent and has been associated with increased risk of preterm delivery. However, comparative effectiveness of 2 commonly used treatment options, mental health counseling and use of antidepressants, in mitigating the risk of preterm delivery associated with maternal depression remains uncertain. Although antidepressant use has been associated with increased risk of preterm delivery in many previous studies, a direct head-to-head comparison between these 2 treatment options has not been investigated. Thus, the comparative risk-benefit profiles of those 2 treatment options remain unclear., Objective: To determine the comparative effectiveness of 2 commonly used options for treating prenatal depression in limiting the risk of preterm delivery associated with maternal depression., Study Design: A large prospective cohort study was conducted among 82,170 pregnant women at Kaiser Permanente Northern California, an integrated health care delivery system. Clinically diagnosed depression and its treatments (use of antidepressants and mental health counseling) were identified from the Kaiser Permanente Northern California electronic health record system. Gestational age was also recorded for all deliveries and captured by electronic health records for determining preterm delivery., Results: Using Cox proportional hazards regression incorporating propensity score methodology to ensure comparability between comparison cohorts, relative to those without depression, pregnant women with untreated depression had 41% increased risk of preterm delivery: adjusted hazard ratio=1.41, 95% confidence interval=1.24 to 1.60, confirming increased risk of preterm delivery associated underlying maternal depression. Relative to untreated depression, any mental health counseling was associated with an 18% of reduced risk of preterm delivery: adjusted hazard ratio=0.82 (0.71-0.96). The inverse association showed a dose-response pattern: increased number of counseling visits was associated with greater reduction in preterm delivery risk with 43% reduction in preterm delivery risk associated with 4 or more visits (adjusted hazard ratio=0.57, 95% confidence interval=0.45-0.73). In contrast, use of antidepressants during pregnancy was associated with an additional 31% increased risk of preterm delivery independent of underlying depression: adjusted hazard ratio=1.31, 95% confidence interval=1.06 to 1.61. This positive association also showed a dose-response relationship: a longer duration of use was associated with an even higher risk., Conclusion: This study provides much needed evidence regarding the comparative effectiveness of 2 common treatment options for prenatal depression in the context of preterm delivery risk. The results indicate that, to reduce preterm delivery risk due to maternal depression, mental health counseling is more effective. Use of antidepressants may add additional risk of preterm delivery, independent of the underlying depression. The findings provide data for clinicians and pregnant women to make informed and evidence-based treatment decisions that take into account the risks and benefits to both maternal and fetal health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Glaucoma, a leading cause of global blindness, is characterized by optic nerve damage and visual field loss. Previous studies have suggested a potential association between glaucoma and anxiety disorders. However, the causal relationship between these two conditions remains unclear., Methods: In this study, we conducted a Mendelian Randomization analysis to investigate the causal relationship between glaucoma and anxiety disorders. We sourced Genome-Wide Association Study (GWAS) datasets for glaucoma and anxiety with the largest sample sizes from the Integrative Epidemiology Unit OpenGWAS (IEU OpenGWAS) project website. Instrumental variables were selected based on specific criteria, and statistical analyses were performed using the R programming language., Results: After filtering and merging the datasets, a total of 60 Single Nucleotide Polymorphisms (SNPs) were obtained for analysis. Regression models were applied to assess the causal relationship between glaucoma and anxiety disorders. The results from all four methods indicated that glaucoma does not cause anxiety disorders ( p > 0.05)., Conclusion: Through rigorous Mendelian Randomization analysis, our findings indicate that glaucoma is not a causative factor for anxiety, with minimal influence from confounding factors in this study. These findings enhance our understanding of the relationship between glaucoma and anxiety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Xu, Chen and Li.)

Background: To describe temporal and sociodemographic patterns of antimicrobial exposure during the first year of life in a large US cohort., Methods: Singleton infants born 1998-2014 enrolled in Kaiser Permanente Northern California integrated health system (n = 345,550) were followed longitudinally via comprehensive electronic health records, capturing all systemic antimicrobial inpatient administrations and outpatient dispensings. Antimicrobial exposure was summarized by maternal and infant characteristics, birth year, inpatient/outpatient status, age in months, and drug class., Results: Overall, 44% of infants in this cohort received at least one dose of antimicrobials during infancy. Decreases over time were driven by reduced outpatient dispensings specifically in later infancy, primarily for penicillins. Among infants receiving any antimicrobials the median number of exposure-days was 16. Inpatient dispensings peaked in the first 30 days of life and outpatient dispensings peaked at 10-11 months. Birth characteristics (i.e., NICU admission, gestational age) were strong independent predictors of antimicrobial exposure between 0- < 3 months; sociodemographic factors were modest predictors of exposure for 3-12 months., Conclusion: Predictors of antimicrobial exposure in early and late infancy are distinct with early infancy exposures highly correlated to birth characteristics. The cumulative proportion of infants exposed has decreased due to fewer late infancy outpatient dispensings., Impact: Comprehensive antimicrobial exposure histories and the maternal and infant characteristics predicting exposure have not been well described in US populations. This analysis provides estimates of cumulative antimicrobial exposures by sociodemographic factors, delivery characteristics, month of life, inpatient/outpatient status, and antibiotic class among one of the largest US HMOs. Predictors of early infancy antimicrobial exposures differ from those in late infancy, with early exposures strongly correlated to birth characteristics and late infancy exposures modestly related to sociodemographic factors. Antimicrobial exposure among infants decreased over the time period primarily due to reduced outpatient dispensings in later infancy., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Preterm birth has been associated with an increased risk of myopia, but the causal relationship between these two factors remains unclear. Traditional epidemiological studies are limited by confounding factors and reverse causality. Mendelian randomization (MR) analysis, utilizing genetic variants as instrumental variables, provides a robust approach to investigate causal relationships. In this study, we aimed to explore the potential causal link between preterm birth and myopia risk using a two-sample MR analysis strategy., Methods: We conducted a Mendelian randomization study to investigate the causal relationship between preterm birth and myopia risk. Genetic variants (single nucleotide polymorphisms, SNPs) were used as instrumental variables, and summary data from genome-wide association studies (GWAS) were utilized. Four regression models, including MR-Egger regression, weighted median regression, inverse variance weighted regression, and Weighted mode regression, were employed to validate the causal relationship. Sensitivity analysis was performed using the leave-one-out method. At the same time, the funnel diagram and MR-Egger test were used to judge the stability of the research results., Results: The MR analysis revealed a significant causal effect of preterm birth on myopia risk. Both the inverse variance weighted regression and weighted median regression models showed a p -value less than 0.05, indicating a robust association. The risk of myopia increased by approximately 30% for everyone standard deviation increase in preterm birth. Sensitivity analysis, funnel plot and MR-Egger test all confirm the stability of the research results., Conclusion: Our findings provide evidence supporting a causal relationship between preterm birth and myopia risk. Preterm infants are at a higher risk of developing myopia, and this association is not likely to be influenced by confounding factors or reverse causality. The SNP loci rs6699397, rs10871582, and rs2570497 should be closely monitored as they may lead to abnormal concentrations of intraocular cytokines, particularly vascular endothelial growth factor, potentially elucidating one of the pathogenic mechanisms contributing to the higher incidence of myopia in preterm infants. However the complex interconnections involved extend beyond these factors alone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lin, Chen and Li.)

Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aimed to investigate the association between residential greenness and tinnitus and the potential interaction between greenness and genetic predisposition to tinnitus. The normalized difference vegetation index (NDVI) is used to measure residential greenness. The tinnitus is defined based on self-reported. In the cross-sectional analyses, logistic regression models are used for the baseline sample of the United Kingdom Biobank cohort. In the secondary analysis, a Cox proportional hazard model is used for a subsample of participants who completed the tinnitus questionnaire at follow-up. In the cross-sectional analysis including 106471 participants, higher residential greenness is associated with lower odds of tinnitus for each interquartile range increase in continuous NDVI, with an adjusted odds ratio of 0.97 (95% confidence interval: 0.95 to 0.99) for tinnitus. A similar association is observed in the longitudinal analysis, with an adjusted hazard ratio of 0.92 (95% confidence interval: 0.86 to 0.98) for the association of NDVI increased per interquartile range with incident tinnitus. Moreover, there is a significant interaction between greenness and genetic predisposition to tinnitus (P < 0.05). This study suggested that residential greenness is negatively associated with tinnitus. Greenness and genetic predisposition to tinnitus are found to have a significant interaction., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways., Objective: To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk., Methods: We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m 2 ) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma., Results: Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m 2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed., Conclusions: Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma., (© 2023 John Wiley & Sons Ltd.)

Background: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs)., Methods: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed., Results: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study., Conclusions: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use., (© 2024. The Author(s).)

Background: Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD., Methods: This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection., Results: A total of 259 patients (mean age 56 ± 14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older ( P  < .001) and have a personal history of visible dysplasia ( P  < .001) and invisible dysplasia ( P  = .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia ( P  < .001). On multivariable analysis, increased age ( P  < .001), increased CWT ( P  = .001), and personal history of visible dysplasia ( P  = .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; P  = .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; P  = .35) is significantly associated with detection of visible dysplasia., Conclusions: For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia., Competing Interests: B.A.-B.: Holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. Speaker fees: AbbVie, Takeda, Bristol-Myers Squibb, Janssen Pharmaceuticals. Advisory board: Bristol-Myers Squibb, Pfizer. J.K.J.G.s: Advisory Board: Bristol-Myers Squibb, Pfizer, Takeda; Consulting: MRM Health. D.D.P.: AbbVie consulting. For the remaining authors, none were declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Recent guidelines do not recommend routine use of aspirin for primary cardiovascular prevention (ppASA) and suggest avoidance of ppASA in older individuals due to bleeding risk. However, ppASA is frequently taken without an appropriate indication. Estimates of the incidence of upper gastrointestinal bleeding due to ppASA in the United States are lacking. In this study, we provide national estimates of upper gastrointestinal bleeding incidence, characteristics, and costs in ppASA users from 2016-2020., Methods: Primary cardiovascular prevention users (patients on long-term aspirin therapy without cardiovascular disease) presenting with upper gastrointestinal bleeding were identified in the Nationwide Emergency Department Sample using International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. Trends in upper gastrointestinal bleeding incidence, etiology, severity, associated Medicare reimbursements, and the impact of ppASA on bleeding outcomes were assessed with regression models., Results: From 2016-2020, adjusted incidence of upper gastrointestinal bleeding increased 29.2% among ppASA users, with larger increases for older patients (increase of 41.6% for age 65-74 years and 36.0% for age ≥75 years). The most common etiology among ppASA users was ulcer disease but increases in bleeding incidence due to angiodysplasias were observed. The proportion of hospitalizations with major complications or comorbidities increased 41.5%, and Medicare reimbursements increased 67.6%. Among patients without cardiovascular disease, ppASA was associated with increased odds of hospital admission, red blood cell transfusion, and endoscopic intervention as compared to no ppASA use., Conclusions: Considering recent guideline recommendations, the rising incidence, severity, and costs associated with upper gastrointestinal bleeding among patients on ppASA highlights the importance of careful assessment for appropriate ppASA use., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship., Methods: This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control's Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range., Results: Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR] = 1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively)., Conclusion: Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.

Twisted van der Waals structures exhibit a variety of unusual electrical and optical phenomena and could provide a powerful means for designing nanodevices with tunable chiral properties. However, programming intrinsic chiral properties of the film on the atomic scale remains a great challenge due to the limitations of fabrication and measurement techniques. Here, we report a highly tunable large optical activity of twisted anisotropic two-dimensional (2D) materials, including black phosphorus (BP), ReS 2 , PdSe 2 , and α-MoO 3 , by varying the twist angle between the stacked layers. The chirality can be deliberately tailored through the engineering of the symmetry, band structure, and anisotropy of 2D materials, demonstrating the high tunability of the chirality. The results show the highest thickness-normalized ellipticity value (13.8 deg μm -1 , twisted ReS 2 ) and ellipticity value (1581 mdeg, twisted BP) among the systems based on 2D materials. It is also shown that the chiroptical response exists in an extremely large spectral range from the visible to the infrared. Furthermore, the twisted ReS 2 enabled spin-selective control of the information transformation. These results show that highly controllable chirality in twisted 2D anisotropic materials has considerable potential in on-chip polarization optics, nano-optoelectronics, and biology.

Aim: To investigate the feasibility of endoscopic dacryocystorhinostomy (En-DCR) with bicanalicular silicone tube intubation for treating chronic dacryocystitis secondary to nasolacrimal duct stent (NDS) incarceration., Methods: En-DCRs were performed on 44 chronic dacryocystitis patients (46 eyes) secondary to NDS incarceration from April 2016 to October 2022. The granuloma and scar tissues were separated, and the removal of NDS incarceration was achieved during the surgery; the flap of the lacrimal sac was trimmed and anastomosed with nasal mucosal, a bicanalicular silicone tube was implanted, and lacrimal size and condition were assessed. The tube was removed 3mo after surgery. During the final follow-up of 12mo when the surgery was completed, the complications and the rates of surgical success were assessed., Results: This study covered 40 patients (42 eyes). Intraoperatively, it was found that the lacrimal sac became small, and the sac wall had granulation and scar tissue attached to the incarcerated NDS in all eyes. At 12mo after surgery completed, the rates of the functional and anatomical success reached 80.95% (34/42) and 83.33% (35/42), respectively. Under the effect of intranasal ostial closure, seven eyes failed to achieve anatomical success. No serious complications ( e.g. , visual impairment, sinusitis, and orbital fat prolapse) was observed., Conclusion: With the success rate over 80% and no serious complications, En-DCR with bicanalicular silicone tube implantation is effective in treating chronic dacryocystitis secondary to NDS incarceration., (International Journal of Ophthalmology Press.)

Background and Aim: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease., Methods: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis., Results: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy., Conclusion: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: Guidelines recommend performing a flexible sigmoidoscopy in patients hospitalized with acute severe ulcerative colitis (ASUC). However, it is unclear if time to sigmoidoscopy affects relevant clinical outcomes. We aimed to assess the impact of early sigmoidoscopy on clinical outcomes using a well-characterized cohort of patients with ASUC., Methods: This is a single-center, retrospective study of all patients hospitalized with ASUC from January 1, 2012 to November 1, 2021. Early sigmoidoscopy was defined as occurring within 72 hours of admission while delayed sigmoidoscopy was defined as occurring >72 hours after admission. Primary outcomes were cumulative days of intravenous (IV) corticosteroid (CS) use, length of hospital stay, and colectomy rates. Secondary outcomes were time to infliximab (IFX) rescue and inpatient opioid medication use., Results: A total of 112 patients hospitalized with ASUC who underwent sigmoidoscopy were included in the analysis. Eighty-seven patients (78%) had early sigmoidoscopy and 25 (22%) had delayed sigmoidoscopy. Patients in the early sigmoidoscopy group were exposed to significantly fewer days of IV CS (4.5 vs 9.2 days; P < .001), had shorter hospital stays (6.4 vs 19.3 days; P < .001), and shorter time to IFX rescue (3.5 vs 6.4 days; P = .004). Rates of colectomy in the early and delayed sigmoidoscopy groups were 17% versus 28%, respectively ( P = .23). Longer time to sigmoidoscopy was associated with a 16% increased risk of colectomy (HR = 1.16, P = .002)., Conclusions: In this well-characterized cohort, early sigmoidoscopy in ASUC was associated with favorable clinical outcomes. These findings highlight the benefits of early sigmoidoscopy in patients with ASUC. Larger prospective studies are needed to corroborate these findings., Competing Interests: B.A.-B.: Speaker honoraria: AbbVie, Takeda. Advisory board: Bristol Meyers Squibb. J.K.J.G.: AbbVie Speaker Bureau. D.D.P.: AbbVie consulting. All other authors have no financial disclosures or conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child's risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk., Methods: Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005-2014) to age 4 (n = 104,467), 6 (n = 63,084), or 8 (n = 31,006) using electronic medical records. Child's asthma was defined using ICD codes and asthma-related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child's asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese 1 [30-34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI., Results: Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI., Conclusions: Higher prepregnancy BMI is associated with modestly increased childhood asthma risk., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Little is known about antidepressant medication use patterns during pregnancy among periconception (before and immediately following conception) users. Additionally, the associations between these patterns and birth outcomes is unclear, after taking into account underlying depression severity., Objective: This study describes patterns of antidepressant use among periconception users and examines associations between usage patterns and birth outcomes., Study Design: This retrospective cohort study included pregnant Kaiser Permanente Northern California (KPNC) members with a live birth between 2014 and 2017 and an antidepressant medication fill that overlapped the 8th week of pregnancy. Outcomes were preterm birth and neonatal intensive care unit (NICU) admission. Data were extracted from KPNC's electronic health records. Modified Poisson regression was conducted., Results: Of the 3637 pregnancies meeting inclusion criteria, 33% (n = 1204) continued antidepressant use throughout the pregnancy (refilled throughout pregnancy), 47% (n = 1721) discontinued use (no refills), and 20% (n = 712) stopped and reinitiated use (refill after 30+ day gap in supply). Women who continued use had 1.86 (95% confidence interval (CI) 1.53, 2.27) times the risk of preterm birth and 1.76 (95% CI: 1.42, 2.19) times the risk of NICU admission, compared to women who discontinued use during pregnancy. Similarly, women with continued use had 1.66 (95% CI: 1.27, 2.18) times the risk of preterm birth and 1.85 (95% CI: 1.39, 2.46) times the risk of NICU admission, compared to women who stopped and reinitiated use. This relationship held when examining continuous exposure; the relationship between continuous exposure and preterm delivery was stronger in later trimesters., Conclusions: Periconception antidepressant users who continue use during pregnancy, particularly into the second and third trimesters, may be at higher risk of adverse birth outcomes. This evidence should be considered alongside the risks associated with depression relapse., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Hospital-based specialty-trained physicians have become more prevalent with emerging data suggesting benefit in consult and procedure volume, reduced complication rates, and increased practice productivity. Interest in gastroenterology (GI) hospitalist programs has increased in recent years. However, little is known regarding the types of GI hospitalist models that currently exist., Aims: To characterize the infrastructure of GI hospitalist models across the USA., Methods: A 50-question survey was distributed to the GI Hospitalist Special Interest Group of the American Society for Gastrointestinal Endoscopy. Information on demographics, hospital infrastructure, and compensation were collected., Results: 31 of 33 (94%) GI hospitalists completed the questionnaire. Respondents were mostly male (65%), white (48%) or Asian (42%). Most GI hospitalists spent at least half of their clinical time dedicated to the inpatient consultation service (73%), during which they had no other clinical duties. Most services had endoscopy suites with dedicated inpatient endoscopy rooms (66%), over 4 h allotted for procedures (83%), and were available on weekends (62%). Over half of GI hospitalists reported having outpatient duties, the most common being performance of direct access endoscopy (69%). Outside of clinical responsibilities, GI hospitalists were most frequently involved in clinical education or fellowship program leadership (48%). Most GI hospitalists were salaried with an incentive-based bonus based on work relative value units., Conclusion: GI hospitalist programs are varied throughout the USA but key commonalities exist between most programs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The adverse consequences of untreated perinatal depression highlight the need to identify populations to target in order to increase treatment rates. The authors sought to evaluate treatment initiation for a new diagnosis of depression during pregnancy or postpartum and to describe racial-ethnic differences in initiation and type (psychotherapy, antidepressants) of treatment in a large health care system with universal perinatal depression screening., Methods: This retrospective cohort study included women who delivered a live birth in the Kaiser Permanente Northern California system between October 2012 and May 2017. Black, Latina, Asian, and White women ages ≥15 years were eligible. New depression diagnoses were defined by using ICD-9 and ICD - 10 codes from electronic health records. Treatment initiation was defined as receiving at least one antidepressant medication dispensation or psychotherapy visit up to 90 days after the diagnosis. Modified Poisson regression was used to estimate the risk for initiating treatment and the type of treatment initiated., Results: In total, 13,637 women with a new depression diagnosis (prenatal: N=7,041, 51.6%; postpartum: N=6,596, 48.4%) were identified. Of the pregnant women, 31.4% initiated treatment, and of the postpartum women, 73.1% initiated treatment. Latina and Asian women were less likely than White women to initiate treatment postpartum. During pregnancy and postpartum, non-White women were more likely to initiate psychotherapy. White women were more likely to initiate antidepressant medication during pregnancy and postpartum or a combination of antidepressant medication and psychotherapy during the postpartum period., Conclusions: Research is warranted to identify patient-, provider-, and system-level barriers that contribute to racial-ethnic disparities in perinatal mental health care.

Background: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age., Methods: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated., Results: Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy., Conclusions: Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants., Competing Interests: A.L.N. reports institutional support from Pfizer and Vir Biotechnology. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers., Methods: Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples., Results: 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro . External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI., Conclusion: The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Liu, Qiu, Tang, Que, Li, Gu, Zhou, Wu, Zhou, Yin and Zuo.)

Success in gene therapy in treating human disease makes this technology attractive to enhance athletic performance, creating the need for gene doping detection. In 2021, World Anti-Doping Agency (WADA) approved the first gene doping test. Here, we describe a new method to detect doping with four additional genes, follistatin, growth hormone 1, growth hormone-releasing hormone and insulin-like growth factor 1, that may improve performance by increasing muscle size and strength. The method utilises four hydrolysis probe-based polymerase chain reaction (PCR) assays that target the transgenes based on the coding sequence of the four endogenous genes. The assays are specific, reproducible and capable to detect five copies of transgene in the presence of very similar endogenous gene in 25,000 times excess. To underpin reliable and comparable routine method performance by doping testing laboratories, a synthetic reference material for the method was designed and generated following the ISO Guide 35. The complete method was validated in blood samples using plasma as extraction matrix and QIAamp DNA blood midi DNA extraction kit. All blood samples from different donors (n = 8) simulated to be negative or positive (1500 transgene copies spiked per millilitre of blood) for the transgenes were reported correctly. The new method that targets four additional genes will extend the capabilities of laboratories involved in doping control to protect athletes' health, fairness and equality., (© 2022 Commonwealth of Australia. Drug Testing and Analysis © 2022 John Wiley & Sons Ltd.)

Background: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden., Methods: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested., Results: Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03-1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [site 2])., Conclusions: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections., Competing Interests: Potential conflicts of interest. A. L. N. received research funding from Pfizer and Vir Biotechnology for unrelated studies (paid to their institution). F. M. participates on data safety monitoring boards for Pfizer (includes a stipend for the author), Moderna (paid to author), Meissa (includes a stipend for the author), Virometix (unpaid participation), and the National Institutes of Health (unpaid participation) and reports grants or contracts from Pfizer (Pediatric COVID-19 Vaccine Study; payment to their institution), Gilead (Pediatric Remdesivir Study; payment to their institution), and the National Institutes of Health (COVID-19 vaccines in pregnant women and Acute Flacid Myelitis Natural History Study; payment to their institution) and royalties or licenses for Up to Date on various chapters and editing (paid to author). M. G. reports several internal grants from Kaiser Permanente Northern California Division of Research for research funding (paid to their institution). M. S. reports other financial or nonfinancial interests from the CDC as a government employee who performed co-authorship duties as part of regular employment. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Combination therapy with thiopurines and anti-tumor necrosis factor (TNF) is superior to monotherapy in Crohn's disease (CD) and ulcerative colitis (UC). The optimal dose of thiopurines in combination therapy remains unclear. We investigated the impact of thiopurine dose in combination therapy on outcomes in inflammatory bowel disease (IBD)., Methods: This was a single-center, retrospective study of patients with IBD treated with thiopurine and anti-TNF combination therapy between 1/2012 and 11/2020. A therapeutic dose of thiopurines was defined as ≥1 mg/kg for 6-mercaptopurine and ≥2 mg/kg for azathioprine. The primary outcome was anti-drug antibody (ADA) formation in patients on a therapeutic thiopurine dose vs. a lower thiopurine dose group. Secondary outcomes included steroid-free clinical remission, endoscopic healing (absence of ulcers/erosions in CD and Mayo endoscopic score ≤1 for UC), and normal serum C-reactive protein (CRP) in patients who were on combination therapy., Results: A total of 108 patients were included (median age 31.5 years; 58.3% male). A therapeutic dose of thiopurine was used in 19%. In the therapeutic thiopurine dose group, 23.8% developed ADA vs. 29.9% (P=0.58) in the lower dose group. No significant differences were noted between the therapeutic and lower dose thiopurine groups in terms of steroid-free clinical remission (57.1% vs. 60.9%, P=0.75), endoscopic healing (55% vs. 60%, P=0.69), and normal CRP (52.4% vs. 52.9%, P=0.27)., Conclusion: In our cohort of patients with IBD on anti-TNF combination therapy, thiopurine dose was not associated with significant differences in anti-TNF immunogenicity and clinical outcomes., Competing Interests: Conflict of Interest: Dr. Badr Al-Bawardy: Speaker Bureau: AbbVie, Takeda. Advisory board: Bristol-Meyers Squibb, Dr. Jill K. J. Gaidos: Speaker Bureau: AbbVie, Advisory Board: Bristol-Myers Squibb All other authors have no disclosures, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Guidelines recommend against aspirin for primary prevention of cardiovascular events in individuals with a history of gastrointestinal bleeding (GIB). It is unknown how often patients on primary prevention aspirin hospitalised with GIB have aspirin discontinued at discharge., Aims: To determine the rate of aspirin deprescription and explore long-term outcomes in patients taking aspirin for primary prevention of cardiovascular events., Methods: We evaluated all patients hospitalised at Yale-New Haven Hospital between January 2014 and October 2021 with GIB who were on aspirin for primary prevention. Our primary endpoint was the frequency of aspirin deprescription at discharge. Our secondary endpoints were post-discharge hospitalisations for major adverse cardiovascular events (MACE) or GIB. Time-to-event analysis was performed using Kaplan-Meier curves and the log-rank test., Results: We identified 320 patients with GIB on aspirin for primary prevention: median age was 72 (interquartile range [IQR] 61-81) years and 297 (92.8%) were on aspirin 81 mg daily. Only 25 (9.0%) patients surviving their hospitalisation were deprescribed aspirin at discharge. Among 260 patients with follow-up (median 1103 days; IQR 367-1670), MACE developed post-discharge in 2/25 (8.0%) with aspirin deprescription versus 37/235 (15.7%) with aspirin continuation (log-rank p = 0.28). 0/25 patients with aspirin deprescription had subsequent hospitalisation for GIB versus 17/235 (7.2%) who continued aspirin (log-rank p = 0.13)., Conclusions: Aspirin for primary cardiovascular prevention was rarely deprescribed at discharge in patients hospitalised with GIB. Processes designed to ensure appropriate deprescription of aspirin are crucial to improve adherence to guidelines, thereby improving the risk-benefit ratio in patients at high risk of subsequent GIB hospitalisations with minimal increased risk of MACE., (© 2022 John Wiley & Sons Ltd.)

Context: M2 phenotype macrophage polarization is an attractive target for therapeutic intervention. Asiaticoside (ATS) has multiple pharmacological functions., Objective: This study investigates the effect of ATS on M2 phenotype macrophage polarization in osteosarcoma., Materials and Methods: The differentiation of human THP-1 monocytes into M0 phenotype macrophages was induced by 100 nM phorbol myristate acetate for 24 h, and treated with 20 ng/mL IL-4 and 20 ng/mL IL-13 for 48 h to obtain M2 phenotype macrophages. The function of ATS on the growth and invasion was investigated by cell counting kit-8, transwell, and western blot under the co-culture of M2 phenotype macrophages and osteosarcoma cells for 24 h. The mechanism of ATS on osteosarcoma was assessed using molecular experiments., Results: ATS reduced the THP-1 cell viability with an IC 50 of 128.67 μM. Also, ATS repressed the M2 phenotype macrophage polarization induced by IL-4/IL-13, and the effect was most notably at a 40 μM dose. ATS (40 μM) restrained the growth and invasion of osteosarcoma cells induced by M2 phenotype macrophages. In addition, ATS reduced the tumour necrosis factor receptor-associated factor 6 (TRAF6)/NF-κB activity in osteosarcoma cells and the TRAF6 knockdown reduced the growth and invasion of osteosarcoma cells induced by M2 phenotype macrophages. TRAF6 (2 μg/mL) attenuated the inhibitory effect of ATS on the growth and invasion of osteosarcoma cells caused by M2 phenotype macrophages. In vivo studies further confirmed ATS (2.5, 5, or 10 mg/kg) repressed osteosarcoma tumour growth., Discussion and Conclusions: ATS reversed M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by reducing TRAF6/NF-κB activity, suggesting ATS might be a promising drug for the clinical treatment of osteosarcoma.

Introduction: Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28 weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system., Methods: The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3 years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22 weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (≤1 year, >1 year and ≤2 years, and >2 years and ≤3 years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits., Results: A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3 years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3 years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition., Conclusions: The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3 years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term.

Esophageal cancer is the eighth most common malignancy worldwide with more than 600,000 new cases diagnosed annually. Although curative approaches to early-stage esophageal cancer have historically been surgical, advances in endoscopic techniques resulted in the identification of patients who may benefit from minimally invasive endoscopic therapies. In this exposition, we discuss the identification of patients who are candidates for endoscopic resection and detail different aspects of endoscopic curative techniques for esophageal neoplasia. We also discuss therapies directed at the palliation of esophageal cancer sequelae., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs)., Objective: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS)., Methods: We measured NfL, GFAP, and MMPs in blood samples from 96 patients with CIS from the MinoCIS study and compared biomarkers with clinical and radiologic characteristics and outcome., Results: At baseline, NfL levels correlated with T 2 lesion load and number of gadolinium-enhancing lesions. Baseline NfL levels predicted conversion into CDMS at month 6. GFAP levels at baseline were correlated with T 2 lesion volume. Minocycline treatment significantly increased NfL levels at 3 months but not at 6 months, and decreased GFAP levels at month 6. Minocycline decreased MMP-7 concentrations at month 1., Discussion: Blood NfL levels are associated with measures of disease activity in CIS and have prognostic value. Minocycline increased NfL levels at month 3, but reduced GFAP and MMP-7 levels.

Background: Intrahepatic cholestasis of pregnancy is associated with a significant risk of stillbirth, which contributes to variation in clinical management. Recent Society for Maternal-Fetal Medicine guidance recommends delivery at 36 weeks of gestation for patients with serum bile acid levels of >100 μmol/L, consideration for delivery between 36 and 39 weeks of gestation stratified by bile acid level, and against preterm delivery for those with clinical features of cholestasis without bile acid elevation., Objective: This study aimed to investigate institutional practices before the publication of the new delivery timing recommendations to establish the maternal and neonatal effects of late preterm, early-term, and term deliveries in the setting of cholestasis., Study Design: This study examined maternal and neonatal outcomes of 441 patients affected by cholestasis delivering 484 neonates in a 4-hospital system over a 30-month period. Logistic and linear regression analyses were performed to assess neonatal outcomes concerning peak serum bile acid levels at various gestational ages controlling for maternal comorbidities, multiple pregnancies, and neonatal birthweight., Results: With the clinical flexibility afforded by the new guidelines, pregnancy prolongation to term may have been achieved in 91 patients (21%), and 286 patients (74%) with bile acid elevation could have delivered at a later gestational age. Preterm deliveries of patients with bile acid levels of >10 μmol/L were associated with higher rates of neonatal intensive care unit admission and adverse neonatal outcomes than early-term deliveries., Conclusion: Study data suggested an opportunity for education and practice change to reflect current Society for Maternal-Fetal Medicine guidelines in efforts to reduce potential neonatal morbidities associated with late preterm deliveries among pregnancies affected by cholestasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Increased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis., (© 2022. The Author(s).)

Background: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described., Materials and Methods: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival., Results: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/μL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P &lt; .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12)., Conclusion: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone., (© The Author(s) 2022. Published by Oxford University Press.)

Purpose: The aim was to explore the clinical efficacy of ranibizumab combined with surgical treatment of neovascular glaucoma with vitreous hemorrhage., Materials and Methods: A total of 15 patients (17 affected eyes) who had neovascular glaucoma (NVG) with vitreous hemorrhage in our hospital were enrolled. After admission, the patient was given levofloxacin eye drops, 4 times a day. Three days later, the patients received intravitreal injection of ranibizumab. Then, trabeculectomy and vitrectomy were performed. The detailed clinical data, such as type of diseases, intraocular pressure (IOP), and best corrected visual acuity (BCVA), were collected before and after surgery., Results: Visual acuity remained stable or improved in thirteen effected eyes and decreased in effected three eyes. Within 30 days after discharge, one effected eye recurred iris neovascularization with slightly higher IOP; then, the patient received intravitreal injection of ranibizumab again and neodymium-doped yttrium aluminum garnet (YAG) therapy. One patient (one effected eye) was given intravitreal ranibizumab injection again because of uncontrollable IOP and recurrence of neovascularization on iris surface and angle after operation; then, the patient received cyclophotocoagulation. Vitreous cavity hemorrhage occurred again in 3 patients after operation; then, these patients received the vitreous cavity lavage again. After trabeculectomy, inflammatory exudation or a small amount of bleeding could be seen in the anterior chamber of 6 young patients., Conclusion: Intravitreal injection of ranibizumab can effectively promote the rapid regression of intraocular neovascularization and help to control the IOP and improve postoperative visual acuity., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Altered host-microbe interactions and increased intestinal permeability have been implicated in disease pathogenesis. However, the mechanisms by which intestinal microbes affect epithelial barrier integrity remain unclear. Here, we investigate the impact of bacterial metabolism of host-produced bile acid (BA) metabolites on epithelial barrier integrity. We observe that rats fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) exhibit reduced intestinal abundance of host-produced conjugated BAs at early time points, coinciding with increased gut permeability. We show that in vitro, conjugated BAs protect gut epithelial monolayers from damage caused by bacterially produced unconjugated BAs through micelle formation. We then demonstrate that inhibition of bacterial BA deconjugation with a small-molecule inhibitor prevents the development of pathologic intestinal permeability and hepatic inflammation in CDAHFD-fed rats. Our study identifies a signaling-independent, physicochemical mechanism for conjugated BA-mediated protection of epithelial barrier function and suggests that rational manipulation of microbial BA metabolism could be leveraged to regulate gut barrier integrity.

Background: Preterm birth is a leading cause of infant mortality, particularly for those born extremely prematurely (EP; <28 weeks' gestational age [GA]). Survivors are predisposed to complications such as bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP)., Aims: To examine the epidemiology, complications, and mortality/survival among EP infants., Study Design: Retrospective analysis of electronic medical records from the Kaiser Permanente Northern California database., Subjects: EP infants live-born between 22 and <28 weeks' GA from 1997 to 2016., Outcome Measures: Cumulative all-cause mortality/survival were analyzed and stratified by GA (22 to <24, 24 to <26, 26 to <28 weeks), complications (BPD/CLD, IVH, ROP), and birth period (1997 to 2003, 2004 to 2009, 2010 to 2016). Cox proportional hazard models were constructed to assess the mortality risk associated with BPD/CLD or IVH., Results: 2154 EP infants were identified; of these, 916 deaths were recorded. Mortality was highest during the first 3 months (41.7 % cumulative mortality), and few were reported after 2 years (42.5 % cumulative mortality). Mortality decreased with higher GA and over more recent birth periods. BPD/CLD and IVH grade 3/4 were associated with increased mortality risk versus no complications (adjusted hazard ratios 1.41 and 1.78, respectively)., Conclusions: The risk of mortality is high during the first few months of life for EP infants, and is even higher for those with BPD and IVH. Despite an overall trend toward increased survival for EP infants, strategies targeting survival of EP infants with these complications are needed., (Copyright © 2022 Takeda Pharmaceuticals Americas Inc. Published by Elsevier B.V. All rights reserved.)

Introduction: Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation and result in increased hospital length of stay (LOS) and healthcare costs. Low-volume bowel preparation (LV-BP; sodium sulfate, potassium sulfate, and magnesium sulfate ) has been shown to improve outpatient bowel preparation quality compared with standard high-volume bowel preparations (HV-BP; polyethylene glycol ). However, its efficacy in hospitalized patients has not been well-studied. We assessed the impact of LV-BP on time to colonoscopy, hospital LOS, and bowel preparation quality among inpatients., Methods: We performed a propensity score-matched analysis of adult inpatients undergoing colonoscopy who received either LV-BP or HV-BP before colonoscopy at a quaternary academic medical center. Multivariate regression models with feature selection were developed to assess the association between LV-BP and study outcomes., Results: Among 1,807 inpatients included in this study, 293 and 1,514 patients received LV-BP and HV-BP, respectively. Among the propensity score-matched population, LV-BP was associated with a shorter time to colonoscopy (β: -0.43 [95% confidence interval: -0.56 to -0.30]) while having similar odds of adequate preparation (odds ratio: 1.02 [95% confidence interval: 0.71-1.46]; P = 0.92). LV-BP was also significantly associated with decreased hospital LOS among older patients (age ≥ 75 years), patients with chronic kidney disease, and patients who were hospitalized with gastrointestinal bleeding., Discussion: LV-BP is associated with decreased time to colonoscopy in hospitalized patients. Older inpatients, inpatients with chronic kidney disease, and inpatients with gastrointestinal bleeding may particularly benefit from LV-BP. Prospective studies are needed to further establish the role of LV-BP for inpatient colonoscopies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: This study aimed to evaluate the association between intrapartum antibiotics (IABX) and asthma and allergic rhinitis among children by ages 6, 8 and 10 years., Design: Retrospective cohort., Setting and Population: Data were collected though Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital between 1997 and 2012 and stayed enrolled through age 6., Methods: Modified Poisson regressions with robust error variances were used to estimate risk ratios for IABX and each outcome at each follow-up age during two separate time periods: 1997-2004 (n = 91 739) and 2005-2012 (n = 108 314)., Main Outcome Measures: Asthma and allergic rhinitis by ages 6, 8 and 10., Results: The proportion of women receiving IABX increased drastically over the study period (from 4% in 1997 to 49% in 2011), while the incidence of asthma (8%) and allergic rhinitis (6%) stayed relatively stable. In adjusted models, risk ratios for the association between IABX and asthma and allergic rhinitis were largely compatible with the null, with some slightly elevated risk ratios observed. For births from 1997 to 2004, risk ratios for asthma were 1.08 (95% CI 1.00-1.17) at age 6, 1.05 (95% CI 0.97-1.15) at age 8, and 1.08 (95% CI 0.99-1.18) at age 10. For births from 2005 to 2012, risk ratios were 1.00 (95% CI 0.95-1.04) at age 6, 1.07 (95% CI 1.01-1.12) at age 8, and 1.11 (95% CI 1.03-1.20) at age 10., Conclusions: Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk., Tweetable Abstract: Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk., (© 2021 John Wiley & Sons Ltd.)