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Cristina F Rabelo,1 Talita Siara Almeida Baptista,2 Laura Esteves Petersen,2 Moisés Evandro Bauer,2 Mauro Waldemar Keiserman,1 Henrique Luiz Staub1 1Department of Rheumatology, 2Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil Introduction: Ankylosing spondylitis (AS) is a chronic disease featuring axial changes, peripheral arthritis and systemic involvement. Proinflammatory cytokines are probably involved in AS pathogenesis. The relationship of circulating cytokines with instruments of AS evaluation is an open field of research.Objective: The aim of this study was to compare serum levels of cytokines in AS patients and healthy controls, and search for correlations of cytokines with indexes of disease activity and quality of life.Patients and methods: In this cross-sectional study, 32 AS patients and 32 age- and sex-matched controls were evaluated. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Funcional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Ankylosing Spondylitis Quality of Life (ASQol) and Patient Global Assessment score were measured in AS patients. . The soluble cytokines IL-6, IL-8, IL-1, IL-10, TNF-α, IL-12p70 and IL-17 were quantified by flow cytometry. IL-23 concentrations were measured using an enzyme-linked immunosorbent assay.Results: Overall, AS patients were predominantly males (59.4%) and Caucasians (96.9%). Mean age was 46.9±10.7 years. Human leukocyte antigen B27 was present in 70% of cases. Concentrations of IL-6, IL-8, IL-10 and TNF-α were higher in AS cases than controls (p

Purpose: Medical school educators face challenges determining which new and emerging topics to incorporate into medical school curricula, and how to do so. A study was conducted to gain a better understanding of the integration of emerging topics related to microbiology and immunology in the undergraduate medical curriculum (UME)., Methods: An anonymous survey with 17 questions was emailed to medical school faculty who teach immunology and/or microbiology through the DR-Ed listserv, the American Society for Microbiology (ASM) Connect listserv, and attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop. Participants were asked about experiences, perceptions, and the decision-making process regarding integrating emerging topics into UME., Results: The top emerging topics that were added to the curriculum or considered for addition in the last 10 years included COVID-19, Zika virus, mRNA vaccines, and Mpox (formerly known as monkeypox). Most respondents reported lectures and active learning as the major methods for topic delivery, with most faculty indicating that formative assessment was the best way to assess emerging topics. Content experts and course directors were the most cited individuals making these decisions. Top reasons for incorporating emerging topics into curricula included preparing students for clinical treatment of cases, followed by demonstrating the importance of basic science, and opportunities to integrate basic science into other disciplines. Challenges for incorporating these topics included making room in an already crowded curriculum, followed by content overload for students., Conclusions: This study describes the rationale for integrating emerging topics related to microbiology and immunology into UME, and identifies the current new and emerging topics, as well as the main methods of integration and assessment. These results may be used by medical educators to inform curricular decisions at their institutions. Future studies will include developing innovative learning modules that overcome barriers to integration.

Obstetric sepsis is a leading cause of maternal mortality and severe maternal morbidity in the United States. However, it is uncommon, and diagnosis and treatment are often delayed. This report summarizes recent work to develop a patient-centered approach for the care of patients with obstetric sepsis. To support patients, educational materials to identify warning signs paired with advocacy tips are important. Following an adverse event, outlines and checklists for patient support are provided. These tools have been developed to address a variety of obstetric conditions and have utility beyond sepsis. On the clinical side, new data to establish a standardized approach to screening and diagnosis is covered in detail. This "two-step" approach has been supported by national obstetric organizations and has similarities to the algorithm used to screen neonates for term early onset sepsis. In addition, the approach for implementation of a sepsis care bundle by the California/Michigan Obstetric Sepsis Quality Collaborative is discussed., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective:  This study aimed to evaluate the safety of peripheral administration of vasopressor agents among patients with circulatory shock., Study Design:  We reviewed the published literature evaluating the use of peripheral norepinephrine in patients with shock and proposed a protocol for use in labor and delivery units., Results:  Peripheral administration of norepinephrine is a safe and potentially lifesaving intervention for patients in labor and delivery with extremely low complication rates., Conclusion:  Adoption of a protocol for peripheral administration of vasopressors in labor and delivery is safe and may prevent life threatening delays in hemodynamic resuscitation., Key Points: · Administering vasopressors through a peripheral line is safe and helps avoid delays in care.. · An established protocol is essential for the safe peripheral administration of vasopressors.. · Understanding continuous blood pressure monitoring is crucial for managing critically ill patients.., Competing Interests: None declared., (Thieme. All rights reserved.)

Recent research has shed light on the intricate relationship between mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), and inflammation. This chapter explores the complex interplay involving immune and metabolic dysfunction in the pathophysiology of these disorders, emphasizing their association with autoimmunity/inflammatory conditions, chronic low-grade systemic inflammation, T cell overactivation, and immunosenescence. This perspective underscores the notion that MDD and BD are not solely brain disorders, highlighting their nature as multi-system conditions., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies., Methods: The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19 th , 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥70% for approval., Results: The accepted criteria for an ageing-related pathology, disease or syndrome were: Develops and/or progresses with increasing chronological age.Should be associated with, or contribute to, functional decline, or an increased susceptibility to functional decline.Evidenced by studies in humans., Conclusions: Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Objectives: Maternal mortality and morbidity disproportionately affect birthing people from racialized populations. Unfortunately, researchers can often compound these poor outcomes through a lack of authentic community engagement in research beyond the role of the research subject, leading to ineffective strategies for improving care and increasing equity. This article details the real-life strategies utilized to develop a community-engaged research project of a phased federally funded grant employing community engagement principles of co-leadership and co-creation. It also includes reflections from the researchers and advisory board on promising practices and lessons learned for equitably engaging patients and community partners in research., Methods: This article details the application of principles of community-engaged research in a federally funded phased research project focused on understanding disparities in maternal sepsis to develop better clinical and community interventions. Specifically, it discusses early steps in the research partnership to create a sustainable partnership with a Community Leadership Board guided by the principles of transparency, respect, compensation, and increasing research justice., Results: Based on the authors' experience, recommendations are provided for funders, researchers, and institutions to improve the quality and outcomes of communityengaged research. This work adds to community-based participatory and community-engaged research literature by providing concrete and practical steps for equitably engaging in research partnerships with a variety of collaborators., Conclusions: In conclusion, integrated patient and community co-leadership enhances research by providing insight, access to communities for education and dissemination of information, and identifying critical areas needing change. This report may help others address fundamental principles in this journey., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Prior studies have shown that maternal deaths due to sepsis occur due to delays in recognition, treatment, and escalation of care through medical chart reviews. This study was conducted to obtain the patient perspective for near-miss and maternal mortality cases due to sepsis., Objective: To identify quality improvement opportunities for improving maternal sepsis through patient and support person experiences., Study Design: Twenty semi-structured interviews and three follow-up focus groups with patients who experienced critical illness from maternal sepsis in the United States and their support persons (when available) were conducted from May 23, 2022, through October 14, 2022. In this qualitative study, data were analyzed using inductive thematic analysis., Results: In this qualitative study of patients with maternal sepsis and their support persons, four main quality improvement themes were identified. The themes were the following: (1) participants reported a lack of awareness of pregnancy-related warning signs and symptoms of when to seek care, (2) many of the presenting symptoms participants experienced were not typical of expected warning signs of maternal sepsis, such as severe pain, overwhelming tiredness, and lack of fever (3) participant concerns were met with dismissal leading to delays in diagnosis, (4) participants experienced long-term sequelae but had difficulty receiving screening and referrals for treatment., Conclusions: The findings of this study suggest that standardized patient education about the warning signs of maternal sepsis and provider education about the presentation of maternal sepsis, improved listening to patients, and follow-up for sequalae of sepsis are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories., Methods: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis., Results: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63)., Discussion: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles., Methods: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry., Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation., Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight., Results: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56 + CD16 - ) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56 + CD16 + ), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4 + CD38 + cells than controls. Contrasting changes were reported in CD25 + CD127 low/neg regulatory T cells, with increased and decreased proportions found in CD4 + and CD8 + T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4 + and CD8 + ) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8 + CD57 + NKG2A + cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19., Conclusions: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight., (© 2024. The Author(s).)

Objective: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions., Methods: This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality Care Collaborative), SIRS (Systemic Inflammatory Response Syndrome), the MEWC (the Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System), and the MEWT (Maternal Early Warning Trigger Tool). Sensitivity, false-positive rates, and C-statistics were reported for each screening tool. Analyses were stratified into cohort 1, which excluded patients with chorioamnionitis-endometritis, and cohort 2, which included those patients., Results: Delivery admissions at 59 hospitals were extracted for patients with sepsis. Cohort 1 comprised 647 patients with sepsis, including 228 with end-organ injury, matched with a control group of 2,588 patients without sepsis. Cohort 2 comprised 14,591 patients with chorioamnionitis-endometritis, of whom 1,049 had sepsis and 238 had end-organ injury. In cohort 1, the CMQCC and the UKOSS pregnancy-adjusted criteria had the lowest false-positive rates (6.9% and 9.6%, respectively) and the highest C-statistics (0.92 and 0.91, respectively). Although other screening criteria, such as SIRS and the MEWC, had similar sensitivities, it was at the cost of much higher false-positive rates (21.3% and 38.3%, respectively). In cohort 2, including all patients with chorioamnionitis-endometritis, the highest C-statistics were again for the CMQCC (0.67) and UKOSS (0.64). All screening tools had high false-positive rates, but the false-positive rates for the CMQCC and UKOSS were substantially lower than those for SIRS and the MEWC., Conclusion: During delivery admissions, the CMQCC and UKOSS pregnancy-adjusted screening criteria have the lowest false-positive results while maintaining greater than 90% sensitivity rates. Performance of all screening tools was degraded in the setting of chorioamnionitis-endometritis., Competing Interests: Financial Disclosure Melissa Bauer reports consulting fees from Institute for Healthcare Innovation. Vesela. Kovacheva reports consulting fees from Avania CRO unrelated to the current work. Paloma Toledo reports speaker fees from Pacira Biosciences, Inc. Kurt Wharton receives consulting fees from Molnlycke. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions., Methods: This was a case-control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non-pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), the MEWC (Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System) obstetric SIRS, and the MEWT (Maternal Early Warning Trigger Tool). Time periods were divided into early pregnancy (less than 20 weeks of gestation), more than 20 weeks of gestation, early postpartum (less than 3 days postpartum), and late postpartum through 42 days. False-positive screening rates, C-statistics, sensitivity, and specificity were reported for each overall screening tool and each individual criterion., Results: We identified 525 patients with sepsis during an antepartum hospitalization and 728 patients with sepsis during a postpartum readmission. For early pregnancy and more than 3 days postpartum, non-pregnancy-adjusted SIRS had the highest C-statistics (0.78 and 0.83, respectively). For more than 20 weeks of gestation and less than 3 days postpartum, the pregnancy-adjusted sepsis screening tools (CMQCC and UKOSS) had the highest C-statistics (0.87-0.94). The MEWC maintained the highest sensitivity rates during all time periods (81.9-94.4%) but also had the highest false-positive rates (30.4-63.9%). The pregnancy-adjusted sepsis screening tools (CMQCC, UKOSS) had the lowest false-positive rates in all time periods (3.9-10.1%). All tools had the lowest C-statistics in the periods of less than 20 weeks of gestation and more than 3 days postpartum., Conclusion: For admissions early in pregnancy and more than 3 days postpartum, non-pregnancy-adjusted sepsis screening tools performed better than pregnancy-adjusted tools. From 20 weeks of gestation through up to 3 days postpartum, using a pregnancy-adjusted sepsis screening tool increased sensitivity and minimized false-positive rates. The overall false-positive rate remained high., Competing Interests: Financial Disclosure Melissa Bauer disclosed receiving consulting fees from the Institute for Healthcare Innovation, and travel compensation from National AIM to present the ACOG/AIM Sepsis Bundle at the ACOG Annual Conference. Vesela Kovacheva disclosed receiving consulting fees from Avania CRO unrelated to the current study. Paloma Toledo disclosed receiving speaker fees from Pacira Biosciences, Inc. Kurt Wharton disclosed receiving consulting fees from Molnlycke. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Postpolypectomy syndrome (PPS) is a relevant adverse event that can appear after polypectomy. Several publications mention postpolypectomy syndrome using different criteria to define it. The aim of this study is to detect potential risk factors and predictors for developing PPS and to define the main criteria of PPS., Methods: In this retrospective monocentric study, 475 out of 966 patients who underwent colonoscopy with polypectomy from October 2015 to June 2020 were included. The main criterion of PPS is defined as the development of postinterventional abdominal pain lasting more than six hours., Results: A total of 9.7% of the patients developed PPS, which was defined as local abdominal pain around the polypectomy area after six hours. A total of 8.6% of the study population had abdominal pain within six hours postintervention. A total of 3.7% had an isolated triad of fever, leukocytosis, and increased CRP in the absence of abdominal pain. Increased CRP combined with an elevated temperature over 37.5 °C seems to be a positive predictor for developing PPS. Four independent risk factors could be detected: serrated polyp morphology, polypoid configurated adenomas, polyp localization in the cecum, and the absence of intraepithelial neoplasia., Conclusions: Four independent risk factors for developing PPS were detected. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology. As expected, the increasing use of cold snare polypectomies will reduce the incidence of this syndrome. Key summary: Our monocentric study on 966 patients detected four independent risk factors for developing PPS: pedunculated polyp, resected polyps in the cecum, absence of IEN, and serrated polyp morphology. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology.

Background: The utility of procalcitonin to identify obstetric sepsis is unknown., Objective: To calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3)., Search Strategy: NLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022., Selection Criteria: Ten or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities., Data Collection and Analysis: Each abstract and full-text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle-Ottawa Scale. A meta-analysis was performed using a random effects model., Main Results: The systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta-analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036-0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049-0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005-1.292 ng/mL)., Conclusions: Among healthy pregnant women not in labor, procalcitonin levels are comparable to those in non-pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non-pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities., Prospero: CRD42020157376, registered 4/28/2020., (© 2023 International Federation of Gynecology and Obstetrics.)

Objectives: This study aimed to verify the performance of the triglyceride-glucose (TyG) index in predicting metabolic syndrome (MetS) using three different criteria in healthy individuals living in rural areas. In addition, it aimed to estimate the TyG index cutoff point in the prediction of MetS., Methods: The study was a cross-sectional study of healthy individuals (aged ≥18 y) living in rural areas of southern Brazil. Individuals with diabetes mellitus were excluded. The variables investigated were waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, fasting glucose, and TyG index. MetS was defined using three criteria: harmonized, International Diabetes Foundation, and National Cholesterol Education Program Adult Treatment Panel III. The Poisson regression model was used for the multivariate analysis. The performance of the TyG index in identifying MetS was determined by receiver operating characteristic curves., Results: A total of 133 individuals were included in this study, with a mean age of 49.0 ± 13.5 y; 54.1% were female. The TyG index performed better in predicting MetS through the harmonized criteria, with area under the curve (AUC) = 0.889 (95% confidence interval [CI], 0.829-0.949), followed by the International Diabetes Foundation criteria, with AUC = 0.877 (95% CI, 0.814-0.940), and the National Cholesterol Education Program criteria, with AUC = 0.867 (95% CI, 0.797-0.937). The TyG index cutoff points defined for the harmonized and International Diabetes Foundation criteria were ≥ 8.61, and ≥ 8.79 for the National Cholesterol Education Program Adult Treatment Panel III., Conclusions: The TyG index proved to be valid for diagnosing MetS. The largest AUC of the TyG index was identified for the harmonized criteria. Thus, the TyG index can be used to diagnose MetS in individuals living in rural areas., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aging is associated with an increased incidence of autoimmune diseases, despite the progressive decline of immune responses (immunosenescence). This apparent paradox can be explained by the age-related chronic low-grade systemic inflammation (inflammaging) and progressive dysregulation of innate signaling. During cellular aging, there is an accumulation of damaged DNA in the cell's cytoplasm, which serves as ubiquitous danger-associated molecule, promptly recognized by DNA sensors. For instance, the free cytoplasmic DNA can be recognized, by DNA-sensing molecules like cGAS-STING (cyclic GMP-AMP synthase linked to a stimulator of interferon genes), triggering transcriptional factors involved in the secretion of pro-inflammatory mediators. However, the contribution of this pathway to the aging immune system remains largely unknown. Here, we highlight recent advances in understanding the biology of the cGAS-STING pathway, its influence on the senescence-associated secretory phenotype (SASP), and its modulation of the immune system during sterile inflammation. We propose that this important stress sensor of DNA damage is also a trigger of immunosenescence and inflammaging., 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 Schmitz, Maurmann, Guma, Bauer and Barbé-Tuana.)

Background: Recent reports indicate that the contribution of deaths related to suicide and overdose are increasing, and may be the leading contributors to maternal mortality up to one year postpartum., Objective: This study aimed to provide a granular assessment of maternal deaths due to suicide or drug overdose in the state of Michigan from 2008 to 2018., Study Design: This retrospective study involved a secondary review of deceased patients' records from 2008 to 2018 stored at the Michigan Department of Health and Human Services through the Michigan Maternal Mortality Surveillance Program. Pregnancy-related and pregnancy-associated deaths were reviewed. A descriptive analysis of maternal characteristics and identified trends was presented in deidentified aggregate form., Results: There were 237 maternal deaths due to suicide or overdose from 2008 to 2018 included in the review. Overall, 70.9% had a documented psychiatric illness in their medical chart, with 48.1% having ≥2 psychiatric illnesses. However, only 34.5% (58/168) of these patients had documentation of taking psychotropic medication for their illness. Of those who died because of accidental or indeterminate substance overdose, 71.1% (138/194) had a known history of substance use disorder. Only 27.4% (43/157) of patients with a documented substance use disorder received medication-assisted treatment. Of those with substance overdose deaths, 42.9% had an opioid prescription, 44.3% had a benzodiazepine prescription, and 32.5% had a prescription for both. Prescription opioids were the most common substance found on postmortem toxicology report, and of these patients, 45.9% had a physician-prescribed opioid., Conclusion: Most pregnant individuals had documented significant risk factors for mental illness or substance use disorder; however, very few had documented pharmacologic therapy for their psychiatric or addiction illness. There is an urgent need to implement effective multidisciplinary health system mitigation strategies that address pregnancy and its intersection with behavioral health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Individuals with severe psychiatric disorders, such as mood disorders and schizophrenia, are at increased risk of developing other medical conditions, especially cardiovascular and metabolic diseases. These medical conditions are underdiagnosed and undertreated in these patients contributing to their increased morbidity and mortality. The basis for this increased comorbidity is not well understood, possibly reflecting shared risks factors (e.g. lifestyle risk factors), shared biological mechanisms and/or reciprocal interactions. Among overlapping pathophysiological mechanisms, inflammation and related factors, such as dysbiosis and insulin resistance, stand out. Besides underlying the association between psychiatric disorders and cardiometabolic diseases, these mechanisms provide several potential therapeutic targets., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Aim: Parental caregivers of children with Down Syndrome (DS) have a greater burden of daily activities that may affect their health. The aim of this exploratory study was to evaluate the impact of caregiving of children with Down syndrome on parenting quality of life, stress, mental and oral health., Methods: Fifty-four parental caregivers of children with DS and 51 parents of children without physical or mental disabilities participated of this study. All participants were clinically examined to evaluate the presence of dental caries, gingival conditions and answered a sociodemographic questionnaire. Depression, anxiety, quality of life and coping strategies were assessed using specific instruments. Hair cortisol level was assessed as biological marker of chronic stress., Results: Psychological and quality of life parameters were similar between the groups of caregivers (p > .05). Caregivers of children with DS were older (48.6 vs. 41.5, p < .001), had longer caregiving period (> 10 vs < 10 years, p = .003), presented higher gingival bleeding index (6.1 vs. 4.7, p = .014) and higher cortisol levels (55.9 vs. 38.4, p = .07) as compared with parents of children without disabilities. Sociodemographic data has no influence on cortisol levels (p > .05)., Conclusions: These findings suggest that the caregiving of children with DS has an impact on parenting oral health and stress., (© 2022 Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: Estimates for the incidence of difficult intubation in the obstetric population vary widely, although previous studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery., Methods: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15 to 44 yr undergoing general anesthesia for cesarean delivery between 2004 and 2019 at 1 of 45 medical centers. Coprimary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view of 3 or greater, three or more intubation attempts, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as any attempt at intubation without successful endotracheal tube placement. The rates of difficult and failed intubation were assessed. Several patient demographic, anatomical, and obstetric factors were evaluated for potential associations with difficult intubation., Results: This study identified 14,748 cases of cesarean delivery performed under general anesthesia. There were 295 cases of difficult intubation, with a frequency of 1:49 (95% CI, 1:55 to 1:44; n = 14,531). There were 18 cases of failed intubation, with a frequency of 1:808 (95% CI, 1:1,276 to 1:511; n = 14,537). Factors with the highest point estimates for the odds of difficult intubation included increased body mass index, Mallampati score III or IV, small hyoid-to-mentum distance, limited jaw protrusion, limited mouth opening, and cervical spine limitations., Conclusions: In this large, multicenter, contemporary study of more than 14,000 general anesthetics for cesarean delivery, an overall risk of difficult intubation of 1:49 and a risk of failed intubation of 1:808 were observed. Most risk factors for difficult intubation were nonobstetric in nature. These data demonstrate that difficult intubation in obstetrics remains an ongoing concern., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Neuraxial anaesthesia is widely utilised for elective caesarean section, but the prevalence of inadequate intra-operative anaesthesia is unclear. We aimed to determine the prevalence of inadequate neuraxial anaesthesia for elective caesarean section; prevalence of conversion from neuraxial anaesthesia to general anaesthesia following inadequate neuraxial anaesthesia; and the effect of mode of anaesthesia. We searched studies reporting inadequate neuraxial anaesthesia that used ≥ ED95 doses (effective dose in 95% of the population) of neuraxial local anaesthetic agents. Our primary outcome was the prevalence of inadequate neuraxial anaesthesia, defined as the need to convert to general anaesthesia; the need to repeat or abandon a planned primary neuraxial technique following incision; unplanned administration of intra-operative analgesia (excluding sedatives); or unplanned epidural drug supplementation. Fifty-four randomised controlled trials were included (3497 patients). The overall prevalence of requirement for supplemental analgesia or anaesthesia was 14.6% (95%CI 13.3-15.9%); 510 out of 3497 patients. The prevalence of general anaesthesia conversion was 2 out of 3497 patients (0.06% (95%CI 0.0-0.2%)). Spinal/combined spinal-epidural anaesthesia was associated with a lower overall prevalence of inadequate neuraxial anaesthesia than epidural anaesthesia (10.2% (95%CI 9.0-11.4%), 278 out of 2732 patients vs. 30.3% (95%CI 26.5-34.5%), 232 out of 765 patients). Further studies are needed to identify risk factors, optimise detection and management strategies and to determine long-term effects of inadequate neuraxial anaesthesia., (© 2022 Association of Anaesthetists.)

Background: The variable presentations and different phenotypes of sepsis suggest that risk of sepsis comes from many genes each having a small effect. The cumulative effect can be used to create individual risk profile. The purpose of this study was to create a polygenic risk score and determine the genetic variants associated with sepsis., Methods: We sequenced ~14 million single nucleotide polymorphisms with a minimac imputation quality R2>0.3 and minor allele frequency >10-6 in patients with Sepsis-2 or Sepsis-3. Genome-wide association was performed using Firth bias-corrected logistic regression. Semi-parsimonious logistic regression was used to create polygenic risk scores and reduced regression to determine the genetic variants independently associated with sepsis., Findings: 2261 patients had sepsis and 13,068 control patients did not. The polygenic risk scores had good discrimination: c-statistic = 0.752 ± 0.005 for Sepsis-2 and 0.752 ± 0.007 for Sepsis-3. We found 772 genetic variants associated with Sepsis-2 and 442 with Sepsis-3, p<0.01. After multivariate adjustment, 100 variants on 85 genes were associated with Sepsis-2 and 69 variants in 54 genes with Sepsis-3. Twenty-five variants were present in both the Sepsis-2 and Sepsis-3 groups out of 32 genes that were present in both groups. The other 7 genes had different variants present. Most variants had small effect sizes., Conclusions: Sepsis-2 and Sepsis-3 have both separate and shared genetic variants. Most genetic variants have small effects sizes, but cumulatively, the polygenic risk scores have good discrimination., Competing Interests: Nicholas Douville was supported by a Foundation for Anesthesia Education and Research (FAER) Mentored Research Training Grant Michael Maile was supported by the American Diabetes Association. Milo Engoren has received consulting fee from Aerogen and Masimo. The other authors have nothing to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: As the field of education was adapting to virtual learning during the COVID-19 pandemic, a need quickly emerged for a course to prepare medical students for future clinical practice. This call to action was answered by creating an innovative Fundamentals of COVID-19 course at the Indiana University School of Medicine (IUSM). As a group of medical student leaders at IUSM, we developed this online course in order to support our fellow students and the community., Methods: The study examined the educational effects of completing the Fundamentals of COVID-19 course. In order to examine these effects, the study asked enrolled students to complete both a pre- and post-course self-assessment survey. Students were asked an identical set of questions on each survey about their knowledge, skills, and abilities (KSA) regarding COVID-19. Composite scores were created for each KSA learning domain. Responses were provided using a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree., Results: Out of the 724 students enrolled, 645 students completed both the pre- and post-course assessment surveys. Findings show that there were both meaningful and statistically significant differences in students' responses to the pre- and post-course surveys. Results show 1.) a significant mean increase in the knowledge composite score of 1.01, 95% CI [0.95, 1.06], t(644) = 36.4, p < .001, d = 1.43; 2.) a significant mean increase in the skills composite score of .55, 95% CI [0.50, 0.60], t(644) = 20.70, p < .001, d = 0.81. and 3.) a significant mean increase of the abilities composite score of 1.02, 95% CI [.97, 1.07], t(644) = 36.56, p < .001, d = 1.44., Conclusions: These findings demonstrate that the student-developed, online Fundamentals of COVID-19 course resulted in notable and statistically significant educational effects. The increase in students' self-reported ratings, especially in the knowledge and abilities domains, indicate that meaningful learning occurred within the course. These findings have notable implications for medical student training during healthcare emergencies, such as a pandemic, as well as within modern clerkship environments. Overall, our findings provide evidence that student-led curricular design and virtual delivery of course content can be effective tools in undergraduate medical education., (© 2022. The Author(s).)

Introduction: The management of nephrolithiasis during pregnancy can be stressful for urologists due to concerns for investigations and treatments that may pose risk of fetal harm, and unfamiliarity with optimal management of these complex patients. In response, we created multi-disciplinary evidence-based guidelines to standardize the care for obstetric patients presenting with flank pain and suspicion for nephrolithiasis. Methods: A multi-disciplinary team involving Urology, Obstetric Anesthesiology, Obstetrics and Gynecology, Diagnostic Radiology, and Interventional Radiology from a single academic medical center was assembled. A PubMed search was performed using keywords of pregnancy/antepartum, nephrolithiasis/calculi/kidney stones, ureteroscopy, non-obstetric surgery, complications, preterm delivery, MRI, computerized tomography, renal bladder ultrasound (RBUS), and anesthesia to identify relevant articles. Team members reviewed their respective areas to create a comprehensive set of guidelines. One invited external expert reviewed the guidelines for validation purposes. Results: A total of 54 articles were reviewed for evidence synthesis. Four guideline statements were constructed to guide diagnosis and imaging, and seven statements to guide intervention. Guidelines were then used to create a diagnostic and intervention flowchart for ease of use. In summary, RBUS should be the initial diagnostic study. If diagnostic uncertainty still exists, a non-contrast CT scan should be obtained. For obstetric patients presenting with a septic obstructing stone, urgent decompression should be achieved. We recommend ureteral stent placement as the preferred intervention if local factors allow. Conclusions: We present a standardized care pathway for the management of nephrolithiasis during pregnancy. Our aim is to standardize and simplify the clinical management of these complex scenarios for urologists., Competing Interests: AK is a consultant for Ambu, Boston Scientific, Lumenis, and Virtuoso Surgical. She is a board member of Sonomotion. WR is a consultant for Boston Scientific. KG is a consultant for Boston Scientific, Lumenis, Coloplast, Olympus, and Karl Storz. The remaining 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 © 2021 Lee, Fenstermaker, Naoum, Chong, Van de Ven, Bauer, Kountanis, Ellis, Shields, Ambani, Krambeck, Roberts and Ghani.)

Background: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake., Methods: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed., Results: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups., Conclusion: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD., Competing Interests: The authors have declared that no competing interests exist.

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Purpose of Review: Maternal sepsis is the second leading cause of maternal death in the United States. A significant number of these deaths are preventable and the purpose of this review is to highlight causes such as delays in recognition and early treatment., Recent Findings: Maternal sepsis can be difficult to diagnose due to significant overlap of symptoms and signs of normal physiological changes of pregnancy, and current screening tools perform poorly to identify sepsis in pregnant women. Surveillance should not only include during pregnancy, but also throughout the postpartum period, up to 42 days postpartum. Education and awareness to highlight this importance are not only vital for obstetric healthcare provides, but also for nonobstetric healthcare providers, patients, and support persons., Summary: Through education and continual review and analysis of evidence-based practice, a reduction in maternal morbidity and mortality secondary to maternal sepsis should be attainable with dedication from all disciplines that care for obstetric and postpartum patients. Education and vigilance also extend to patients and support persons who should be empowered to escalate care when needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Penicillin allergy is reported in up to 10% of the general population; however, >90% of patients reporting an allergy are tolerant. Patients labeled as penicillin allergic have longer hospital stays, increased exposure to suboptimal antibiotics, and an increased risk of methicillin-resistant Staphylococcus aureus and Clostridioides difficile . The primary aim with our quality improvement initiative was to increase penicillin allergy delabeling to at least 10% among all hospitalized pediatric patients reporting a penicillin allergy with efforts directed toward patients determined to be low risk for true allergic reaction., Methods: Our quality improvement project included several interventions: the development of a multidisciplinary clinical care pathway to identify eligible patients, workflow optimization to support delabeling, an educational intervention, and participation in our institution's quality improvement incentive program. Our interventions were targeted to facilitate appropriate delabeling by the primary hospital medicine team. Statistical process control charts were used to assess the impact of this intervention pre- and postpathway implementation., Results: After implementation of the clinical pathway, the percentage of patients admitted to hospital medicine delabeled of their penicillin allergy by discharge increased to 11.7%. More than one-half of those delabeled (51.2%) received a penicillin-based antimicrobial at time of discharge. There have been no adverse events or allergic reactions requiring emergency medication administration since pathway implementation., Conclusions: Our quality improvement initiative successfully increased the rate of penicillin allergy delabeling among low-risk hospitalized pediatric patients, allowing for increased use of optimal antibiotics., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. However, the mechanisms underlying this enhanced inflammation are not well understood. There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context. Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells). Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as: (i) failure to develop adequate stress-related responses, (ii) indirectly through microglial activation, (iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and (iv) dysbiosis. In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders. A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies., (© 2021 S. Karger AG, Basel.)

Background: This study aims to investigate the relationship between the birth experience and the risk of developing postpartum depression or post-traumatic stress disorder., Methods: In this prospective, longitudinal, observational study, women were assessed at different time points for depression and post-traumatic stress disorder. The risk of depression or post-traumatic stress disorder based on patient characteristics and specific birth events was assessed within three months postpartum., Results: We enrolled 600 women; 426 were eligible for postpartum assessment. At six weeks and three months postpartum, 15.9% and 12.7% screened positive for depression respectively. Positive post-traumatic stress disorder screenings at six weeks and three months postpartum were 6.2% and 5.1% respectively. Twenty-seven women (8.3%) with a negative screening at six weeks converted to a positive depression or post-traumatic stress disorder screening at three months. A pre-existing history of anxiety or depression was associated with an increased risk of developing depression (aOR 2.12, 95% CI 1.30 to 3.47) and post-traumatic stress (aOR 3.15, 95% CI 1.42 to 7.02) within three months postpartum. The risk of developing post-traumatic stress disorder within three months postpartum was also increased among patients experiencing their first delivery (aOR 2.55, 95% CI 1.10 to 5.88) or operative management of postpartum hemorrhage (aOR 4.44, 95% CI 1.16 to 17.02)., Conclusion: Depression and post-traumatic stress symptoms either persisted or had new onset at three months postpartum. Mental health screening and postpartum follow-up after six weeks should be considered in high-risk patients who have a history of psychopathology, nulliparity, or undergo operative management of postpartum hemorrhage., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the association between opioid prescribing during pregnancy and new persistent opioid use in the year following delivery., Materials and Methods: This nationwide retrospective cohort study included patients aged 12-55 years in Optum's deidentified Clinformatics Data Mart Database who were undergoing vaginal delivery or cesarean delivery from 2008 to 2016, with continuous enrollment from 2 years before birth to 1 year postdischarge. Women were included if they were opioid naive in pregnancy (ie, did not fill an opioid prescription 2 years to 9 months before delivery) and did not undergo a procedure within the year after discharge. The exposure was filling an opioid prescription in pregnancy. The primary outcome was new persistent opioid use, defined as a pharmacy claim for ≥1 opioid prescription between 4 and 90 days postdischarge and ≥1 prescription between 91 and 365 days postdischarge. Clinical and demographic covariates were included. Analyses included descriptive statistics and multivariable logistic regression, adjusting for clinical and demographic covariates., Results: Of 158,425 childbirths identified, 101,013 (63.8%) were by vaginal delivery and 57,412 (36.2%) cesarean delivery. Among all patients, 6.0% (9429) filled an opioid prescription during pregnancy. The factors associated with filling an opioid in pregnancy were having a nondelivery procedure in pregnancy (adjusted odds ratio, 9.60; 95% confidence interval, 8.81-10.47) and having an emergency room visit during pregnancy (adjusted odds ratio, 2.48; 95% confidence interval, 2.37-2.59). Of women who received an opioid in pregnancy, 4% (379) developed new persistent opioid use. The factors most associated with new persistent opioid use were receiving an opioid prescription during pregnancy (adjusted odds ratio, 3.45; 95% confidence interval, 3.04-3.92) and filling a peripartum opioid prescription (1 week prior to 3 days postdischarge) adjusted odds ratio, 2.28, 95% confidence interval (2.02-2.57). Though having a procedure during pregnancy was associated with increased receipt of an opioid prescription, it was also associated with reduced new persistent opioid use (adjusted odds ratio, 0.72; 95% confidence interval, 0.52-0.99)., Conclusion: Women who receive an opioid prescription during pregnancy are more likely to experience new persistent opioid use. Maternity care providers must balance pain management in pregnancy with potential risks of opioids., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aging immune system (immunosenescence) has been implicated with increased morbidity and mortality in the elderly. Of note, T cell aging and low-grade inflammation (inflammaging) are implicated with several age-related conditions. The expansion of late-differentiated T cells (CD28 - ), regulatory T cells, increased serum levels of autoantibodies, and pro-inflammatory cytokines were implicated with morbidities during aging. Features of accelerated immunosenescence can be identified in adults with chronic inflammatory conditions, such as rheumatoid arthritis, and are predictive of poor clinical outcomes. Therefore, there is an interplay between immunosenescence and age-related diseases. In this review, we discuss how the aging immune system may contribute to the development and clinical course of age-related diseases such as neurodegenerative diseases, rheumatoid arthritis, cancer, cardiovascular, and metabolic diseases.

This survey study evaluates the user experience of an electronic maternal early warning system that generates automated pages. Survey domains included the system's effect on patient care, alarm fatigue, and continued use of the system. The response rate was 47.7% (273 of 572). A majority, 83%, felt that the system should remain in use, and 64.5% felt it improved patient safety. Of those who believed that they had received a page, 51.4% felt that they received pages "too frequently." Although alarm fatigue was not fully evaluated, providers on our unit support the continued use of this automated maternal electronic surveillance system.

Background: A leading cause of preventable maternal death is related to delayed response to clinical warning signs. Electronic surveillance systems may improve detection of maternal morbidity with automated notifications. This retrospective observational study evaluates the ability of an automated surveillance system and the Maternal Early Warning Criteria (MEWC) to detect severely morbid postpartum hemorrhage (sPPH) after delivery., Methods: The electronic health records of adult obstetric patients of any gestational age delivering between April 1, 2017 and December 1, 2018 were queried to identify scheduled or unscheduled vaginal or cesarean deliveries. Deliveries complicated by sPPH were identified and defined by operative management of postpartum hemorrhage, transfusion of ≥4 units of packed red blood cells (pRBCs), ≥2 units of pRBCs and ≥2 units of fresh-frozen plasma, transfusion with >1 dose of furosemide, or transfer to the intensive care unit. The test characteristics of automated pages and the MEWC for identification of sPPH 24 hours after delivery were determined and compared using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and their 95% confidence intervals (CIs). McNemar test was used to compare these estimates for both early warning systems., Results: The average age at admission was 30.7 years (standard deviation [SD] = 5.1 years), mean gestational age 38 weeks 4 days, and cesarean delivery accounted for 30.0% of deliveries. Of 7853 deliveries, 120 (1.5%) were complicated by sPPH. The sensitivity of automated pages for sPPH within 24 hours of delivery was 60.8% (95% CI, 52.1-69.6), specificity 82.5% (95% CI, 81.7-83.4), PPV 5.1% (95% CI, 4.0-6.3), and NPV 99.3% (95% CI, 99.1-99.5). The test characteristics of the MEWC for sPPH were sensitivity 75.0% (95% CI, 67.3-82.7), specificity 66.3% (95% CI, 65.2-67.3), PPV 3.3% (95% CI, 2.7-4.0), and NPV 99.4% (95% CI, 99.2-99.6). There were 10 sPPH cases identified by automated pages, but not by the MEWC. Six of these cases were identified by a page for anemia, and 4 cases were the result of vital signs detected by the bedside monitor, but not recorded in the patient's medical record by the bedside nurse. Therefore, the combined sensitivity of the 2 systems was 83.3% (95% CI, 75.4-89.5)., Conclusions: The automated system identified 10 of 120 deliveries complicated by sPPH not identified by the MEWC. Using an automated alerting system in combination with a labor and delivery unit's existing nursing-driven early warning system may improve detection of sPPH.

Background The use of extracorporeal life support (ECLS) has expanded to include unique populations such as peripartum women. This systematic review aims to (1) quantify the number of cases and indications for ECLS in women during the peripartum period reported in the literature and (2) report maternal and fetal complications and outcomes associated with peripartum ECLS. Methods and Results This review was registered in PROSPERO (CRD42018108142). MEDLINE, Embase, and CINAHL were searched for case reports, case series, and studies reporting cases of ECLS during the peripartum period that reported one or more of the following outcomes: maternal survival, maternal complications, fetal survival, and/or fetal complications. Qualitative assessment of 221 publications evaluated the number of cases, clinical details, and maternal and fetal outcomes of ECLS during the peripartum period. There were 358 women included and 68 reported fetal outcomes in cases where the mother was pregnant at the time of cannulation. The aggregate maternal survival at 30 days was 270 (75.4%) and at 1 year was 266 (74.3%); fetal survival was 44 (64.7%). The most common indications for ECLS overall in pregnancy included acute respiratory distress syndrome 177 (49.4%), cardiac failure 67 (18.7%), and cardiac arrest 57 (15.9%). The most common maternal complications included mild to moderate bleeding 66 (18.4%), severe bleeding requiring surgical intervention 48 (13.4%), and intracranial neurologic morbidity 19 (5.3%). The most commonly reported fetal complications included preterm delivery 33 (48.5%) and neonatal intensive care unit admission 19 (27.9%). Conclusions Reported rates of survival in ECLS in pregnant and postpartum women are high and major complications relatively low.

Information on colored dissolved organic matter (CDOM) is essential for understanding and managing lakes but is often not available, especially in lake-rich regions where concentrations are often highly variable in time and space. We developed remote sensing methods that can use both Landsat and Sentinel satellite imagery to provide census-level CDOM measurements across the state of Minnesota, USA, a lake-rich landscape with highly varied lake, watershed, and climatic conditions. We evaluated the error of satellite derived CDOM resulting from two atmospheric correction methods with in situ data, and found that both provided substantial improvements over previous methods. We applied CDOM models to 2015 and 2016 Landsat 8 OLI imagery to create 2015 and 2016 Minnesota statewide CDOM maps (reported as absorption coefficients at 440 nm, a 440 ) and used those maps to conduct a geospatial analysis at the ecoregion level. Large differences in a 440 among ecoregions were related to predominant land cover/use; lakes in ecoregions with large areas of wetland and forest had significantly higher CDOM levels than lakes in agricultural ecoregions. We compared regional lake CDOM levels between two years with strongly contrasting precipitation (close-to-normal precipitation year in 2015 and much wetter conditions with large storm events in 2016). CDOM levels of lakes in agricultural ecoregions tended to decrease between 2015 and 2016, probably because of dilution by rainfall, and 7% of lakes in these areas decreased in a 440 by ≥3 m - 1 . In two ecoregions with high forest and wetlands cover, a 440 increased by >3 m - 1 in 28 and 31% of the lakes, probably due to enhanced transport of CDOM from forested wetlands. With appropriate model tuning and validation, the approach we describe could be extended to other regions, providing a method for frequent and comprehensive measurements of CDOM, a dynamic and important variable in surface waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

With increasing numbers of coronavirus disease 2019 (COVID-19) cases due to efficient human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States, preparation for the unpredictable setting of labor and delivery is paramount. The priorities are 2-fold in the management of obstetric patients with COVID-19 infection or persons under investigation (PUI): (1) caring for the range of asymptomatic to critically ill pregnant and postpartum women; (2) protecting health care workers and beyond from exposure during the delivery hospitalization (health care providers, personnel, family members). The goal of this review is to provide evidence-based recommendations or, when evidence is limited, expert opinion for anesthesiologists caring for pregnant women during the COVID-19 pandemic with a focus on preparedness and best clinical obstetric anesthesia practice.