Implementation and Clinical Impact of a Guideline for Standardized, Evidence-Based Induction of Labor.

OBJECTIVE: This study aimed to assess the impact of implementation of an induction of labor (IOL) guideline on IOL length and utilization of evidence-based practices. STUDY DESIGN: We conducted a quality improvement project to increase utilization of three evidence-based IOL practices: combined agent ripening, vaginal misoprostol, and early amniotomy. Singletons with intact membranes and cervical dilation ≤2 cm admitted for IOL were included. Primary outcome was IOL length. Secondary outcomes included cesarean delivery and practice utilization. We compared preimplementation (PRE; November 1, 2021 through January 31, 2022) to postimplementation (POST; March 1, 2022 through April 30, 2022) with sensitivity analyses by self-reported race and ethnicity. Cox proportional hazards models and logistic regression were used to test the association between period and outcomes. RESULTS: Among 495 birthing people (PRE, n = 293; POST, n = 202), IOL length was shorter POST (22.0 vs. 18.3 h, p = 0.003), with faster time to delivery (adjusted hazard ratio [aHR] 1.38, 95% CI 1.15-1.66), more birthing people delivered within 24 hours (57 vs. 68.8%, adjusted odds ratio [aOR] 1.90 [95% CI 1.25-2.89]), and no difference in cesarean. Utilization of combined agent ripening (31.1 vs. 42.6%, p = 0.009), vaginal misoprostol (34.5 vs. 68.3%, p < 0.001), and early amniotomy (19.1 vs. 31.7%, p = 0.001) increased POST. CONCLUSION: Implementation of an evidence-based IOL guideline is associated with shorter induction time. Additional implementation efforts to increase adoption of practices are needed to optimize outcomes after IOL. KEY POINTS: · Implementation of an IOL guideline is associated with faster time to delivery.. · Evidence-based induction practices were used more often after guideline implementation.. · Adoption of evidence-based induction practices is variable even with a guideline..

Regulation of Versican Expression in Macrophages is Mediated by Canonical Type I Interferon Signaling via ISGF3.

Growing evidence supports a role for versican as an important component of the inflammatory response, with both pro- and anti-inflammatory roles depending on the specific context of the system or disease under investigation. Our goal is to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. In previous work, we showed that LPS triggers a signaling cascade involving TLR4, the Trif adaptor, type I interferons, and the type I interferon receptor, leading to increased versican expression by macrophages. In the present study, we used a combination of chromatin immunoprecipitation, siRNA, chemical inhibitors, and mouse model approaches to investigate the regulatory events downstream of the type I interferon receptor to better define the mechanism controlling versican expression. Results indicate that transcriptional regulation by canonical type I interferon signaling via the heterotrimeric transcription factor, ISGF3, controls versican expression in macrophages exposed to LPS. This pathway is not dependent on MAPK signaling, which has been shown to regulate versican expression in other cell types. The stability of versican mRNA may also contribute to prolonged versican expression in macrophages. These findings strongly support a role for macrophage-derived versican as a type I interferon-stimulated gene and further our understanding of versican's role in regulating inflammation.

Ammonia for Determination of Cage-change Frequency in Antelope Ground Squirrels (Ammospermophilus leucurus).

Due to a lack of evidence-based standards for cage-change intervals for antelope ground squirrels (AGS, Ammospermophilus leucurus), we evaluated cage ammonia accumulation in our colony of adult, wild-caught AGS and identified factors that influenced ammonia levels. Intracage ammonia was measured daily in singly housed AGS in static caging that contained a running wheel and 1/2, 3/4, 1, or 2 quart (qt) of corncob bedding. Cages were changed when ammonia levels reached greater than 50 ppm, our upper acceptable limit for ammonia based on mouse studies of ammonia aversion and toxicity. We also measured average daily water consumption over 2 wk to examine any correlation between water use and ammonia accumulation. We hypothesized that the desert-dwelling AGS would not reach intracage ammonia levels of greater than 50 ppm in a 2-wk interval at any bedding volume. Our data showed that intracage ammonia was highly variable among individuals and was significantly associated with water consumption and bedding volumes. Seventeen percent of AGS on 1/2 qt of bedding and 18% on 3/4 qt of bedding reached greater than 50 ppm ammonia before 7 d. All AGS on 1 and 2 qt of bedding remained below 50 ppm ammonia for 1 wk. Even when maintained on 2 qt of bedding, not all AGS remained below 50 ppm ammonia for 2 wk. Therefore, we concluded that the most appropriate option was weekly cage change for singly housed AGS on 1 qt of bedding in static caging.

Antimicrobial effects of cannabidiol on select agriculturally important Clostridia.

Amino acid-fermenting Clostridia have undesirable effects in agricultural systems, which can be mitigated by antibiotics, but resistance necessitates alternatives. Here, we demonstrate the efficacy of cannabidiol on growth and ammonia inhibition of five agriculturally relevant Clostridia: Clostridium sporogenes, Peptostreptococcus spp., Clostridioides difficile, Acetoanaerobium sticklandii, and Clostridium aminophilum.

Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung.

The inter-alpha-trypsin inhibitor (IαI) complex is composed of the bikunin core protein with a single chondroitin sulfate (CS) attached and one or two heavy chains (HCs) covalently linked to the CS chain. The HCs from IαI can be transferred to hyaluronan (HA) through a TNFα-stimulated gene-6 (TSG-6) dependent process to form an HC•HA matrix. Previous studies reported increased IαI, HA, and HC•HA complexes in mouse bronchoalveolar lavage fluid (BALF) post-influenza infection. However, the expression and incorporation of HCs into the HA matrix of the lungs during the clinical course of influenza A virus (IAV) infection and the biological significance of the HC•HA matrix are poorly understood. The present study aimed to better understand the composition of HC•HA matrices in mice infected with IAV and how these matrices regulate the host pulmonary immune response. In IAV infected mice bikunin, HC1-3, TSG-6, and HAS1-3 all show increased gene expression at various times during a 12-day clinical course. The increased accumulation of IαI and HA was confirmed in the lungs of infected mice using immunohistochemistry and quantitative digital pathology. Western blots confirmed increases in the IαI components in BALF and lung tissue at 6 days post-infection (dpi). Interestingly, HCs and bikunin recovered from BALF and plasma from mice 6 dpi with IAV, displayed differences in the HC composition by Western blot analysis and differences in bikunin's CS chain sulfation patterns by mass spectrometry analysis. This strongly suggests that the IαI components were synthesized in the lungs rather than translocated from the vascular compartment. HA was significantly increased in BALF at 6 dpi, and the HA recovered in BALF and lung tissues were modified with HCs indicating the presence of an HC•HA matrix. In vitro experiments using polyinosinic-polycytidylic acid (poly(I:C)) treated mouse lung fibroblasts (MLF) showed that modification of HA with HCs increased cell-associated HA, and that this increase was due to the retention of HA in the MLF glycocalyx. In vitro studies of leukocyte adhesion showed differential binding of lymphoid (Hut78), monocyte (U937), and neutrophil (dHL60) cell lines to HA and HC•HA matrices. Hut78 cells adhered to immobilized HA in a size and concentration-dependent manner. In contrast, the binding of dHL60 and U937 cells depended on generating a HC•HA matrix by MLF. Our in vivo findings, using multiple bronchoalveolar lavages, correlated with our in vitro findings in that lymphoid cells bound more tightly to the HA-glycocalyx in the lungs of influenza-infected mice than neutrophils and mononuclear phagocytes (MNPs). The neutrophils and MNPs were associated with a HC•HA matrix and were more readily lavaged from the lungs. In conclusion, this work shows increased IαI and HA accumulation and the formation of a HC•HA matrix in mouse lungs post-IAV infection. The formation of HA and HC•HA matrices could potentially create specific microenvironments in the lungs for immune cell recruitment and activation during IAV infection.

Creatine kinase and its isoenzymes in the serum and cerebrospinal fluid of healthy canines.

BACKGROUND: Creatine kinase (CK) exists as three isoenzymes (CK-MM, CK-MB, and CK-BB) that are predominantly expressed in specific tissues and can be detected in both the serum and cerebrospinal fluid (CSF). CSF CK has been relatively unstudied in veterinary medicine, although studies in human medicine have demonstrated that changes in total CSF CK activity can indicate neurologic abnormalities. OBJECTIVES: The purpose of this study was to establish reference intervals for CK and its three major isoenzymes in the serum and CSF of clinically healthy dogs. By establishing a definitive reference interval for this enzyme in healthy canines, the diagnostic use and possible significance of CK in clinical disease can be studied. METHODS: Serum and/or CSF were collected from healthy dogs. Total CK activity was measured spectrophotometrically, and isoenzyme distributions were determined using the QuickGel CK Vis Isoenzyme Kit and a densitometric scanner. Total CK and CK isoenzyme activities were determined within 8 h of collection. RESULTS: The median serum total CK in healthy canines was 159.0 U/L (range: 53.0-539.0 U/L), while the median CSF total CK was 3.7 U/L (range: 2.0-84.0 U/L). CK-BB and CK-MM were approximately equal in the serum, while CK-MM was the predominant isoenzyme in the CSF. CONCLUSIONS: Knowledge of the normal distribution and concentration of CK in canine serum and CSF will set the foundation for future studies of canine CK as a potentially clinically useful biomarker.

Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria.

OBJECTIVES: This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microbiota by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. METHODS: In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine - exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. RESULTS: Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 µM nicotine and 10 µM cotinine concentrations reduced total protein cargo of Gram (-) - 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 µM nicotine, and 5 or 10 µΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. CONCLUSIONS: Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.

Multicompartmental analysis of the murine pulmonary immune response by spectral flow cytometry.

Studies of pulmonary inflammation require unique considerations due to the complex structure and composition of the lungs. The lungs have multiple compartments and diverse immune cell populations, with inherently high autofluorescence, and are involved in the host response to pulmonary pathogens. We describe a protocol that accounts for these factors through a novel combination of methodologies-in vivo compartmental analysis and spectral flow cytometry with a broad panel of antibodies. In vivo compartmental analysis enables the precise localization of immune cells within the marginated vasculature, lung interstitium, nonlavageable airways, and lavageable airways of the lungs, as well as the pulmonary lymph nodes. Spectral flow cytometry with a broad panel of antibodies supports an unbiased exploratory approach to investigating diverse immune cell populations during pulmonary inflammation. Most importantly, spectral flow uses cellular autofluorescence to aid in the resolution and identification of immune cell populations. This methodology enables the acquisition of high-quality data compatible with informed gating and dimensionality reduction algorithms. In addition, our protocol emphasizes considerations for compartmentalization of the inflammatory response, spectral flow panel design, and autofluorescence spectra analysis. These methodologies are critical for increasing the rigor of pulmonary research. We apply this protocol for the precise characterization and localization of leukocytes in the pulmonary host response to influenza A virus in C57BL/6J mice. In particular, we demonstrate that this protocol improves the quantification and localization of alveolar macrophages within the airways. The methodology is modifiable and expandable to allow for further characterization of leukocyte populations of special interest.NEW & NOTEWORTHY We describe a novel combination of methodologies that incorporates dual in vivo compartmental analysis using intravascular and intratracheal CD45 labeling, a broad panel of antibodies for identifying lymphoid and nonlymphoid cells, and spectral flow cytometry that uses cellular autofluorescence to aid in resolving and identifying immune cell populations. This methodology allows precise localization of immune cells in the lavageable airways, nonlavageable airways, interstitial lung tissue, and marginated in the lung vasculature.

Contemporary Obstetric and Neonatal Outcomes in Sickle Cell Disease: A Retrospective Cohort Study.

OBJECTIVE: Sickle cell disease is associated with adverse perinatal outcomes. Aspects of sickle cell disease in pregnancy, such as health care utilization and neonatal abstinence syndrome, are understudied. We aimed to describe contemporary sickle cell disease outcomes in a U.S. hospital system to improve perinatal counseling. STUDY DESIGN: We conducted a retrospective cohort study of patients with sickle cell disease who delivered at >20 weeks' gestation at two sites within the University of Pennsylvania Health System from May 1, 2017 to August 30, 2020. Descriptive statistics were utilized. RESULTS: Over the study period, 48 patients with sickle cell disease had 52 deliveries of 53 neonates. Sickle cell disease-related morbidity was prevalent prior to pregnancy; 27% had a history of avascular necrosis, and 58% had experienced acute chest syndrome. In the year prior to pregnancy, 52% used daily opioids. During pregnancy, more than half of patients were admitted at least once for sickle cell disease-related complications, spending a median 3 days admitted interquartile range (0-23); >10% spent >70 days of pregnancy admitted. New daily opioids were prescribed during pregnancy for 10% to manage pain crises. Acute chest syndrome was experienced by 23% of patients during pregnancy, and 8% required placement of long-term intravenous access. Preterm delivery <37 weeks occurred in 48%. The primary cesarean rate in nulliparas was 43%. Additionally, 50% experienced a hypertensive disorder of pregnancy, 35% underwent transfusion during delivery admission, and 10% had a perinatal venous thromboembolism. Finally, 53% of neonates were admitted to the intensive care unit. Low birth weight was noted in 34%, severe respiratory distress in 15% of infants, and neonatal abstinence syndrome in 21%. CONCLUSION: Sickle cell disease remains associated with significant perinatal morbidity and need for hospitalization. These data provide contemporary outcomes to target improvements in the care of patients with sickle cell disease. KEY POINTS: · SCD was associated with significant perinatal morbidity and healthcare utilization.. · Most patients with SCD required hospitalization during pregnancy.. · Neonates of patients with SCD experienced preterm birth, NICU admission, and neonatal abstinence syndrome..

Electronic Reminder to Transition Care After Hypertensive Disorders of Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: Scalable interventions are needed to improve preventive care for those with increased cardiovascular disease (CVD) risk identified during pregnancy. We hypothesized that an automated reminder message for clinicians (nudge) would increase counseling at the postpartum visit on patient transitions of care. METHODS: We conducted a single-center, randomized controlled trial including birthing people with a hypertensive disorder of pregnancy evaluating a nudge compared with usual care. The nudge, including counseling phrases and patient-specific information on hypertensive diagnosis, was sent to the obstetric clinician through the electronic medical record up to 7 days before the postpartum visit. The primary outcome was documentation of counseling on transitions of care to primary care or cardiology. Secondary outcomes were documentation of CVD risk, use of counseling phrases, and preventive care visit within 6 months. A sample size of 94 per group (n=188) was planned to compare the nudge intervention with usual care; given the anticipated loss to follow-up, the sample size was increased to 222. Intention-to-treat analyses were performed, with P <.05 considered significant. RESULTS: From February to June 2021, 392 patients were screened, and 222 were randomized and analyzed. Of these, 205 (92.3%) attended a postpartum visit. Groups were similar, but more women in the usual care group had diabetes (16.1% vs 6.7%, P =.03). After adjustment for diabetes, patients in the nudge group were more likely to have documented counseling on transitions of care (38.8% vs 26.2%, adjusted relative risk [aRR] 1.53, 95% CI 1.02-2.31), CVD risk (21.4% vs 8.4%, aRR 2.57, 95% CI 1.20-5.49), and use of aspirin in a future pregnancy (14.3% vs 1.9%, aRR 7.49, 95% CI 1.66-33.93). Counseling phrases were used more often in the nudge group (11.2% vs 0.9%, aRR 12.27, 95% CI 1.50-100.28). Preventive care visit attendance did not differ by group (22.1% vs 24.6%, aRR 0.91, 95% CI 0.57-1.47). CONCLUSION: A timely electronic reminder to obstetric clinicians improved counseling about transitions of care after hypertensive disorders of pregnancy but did not result in increased preventive care visit attendance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04660032.

Sun exposure, a relevant exposome factor in acne patients and how photoprotection can improve outcomes.

BACKGROUND: Acne pathophysiology includes a complex interaction among inflammatory mediators, hyperseborrhea, alteration of keratinization and follicular colonization by Propionibacterium acnes. AIMS: To describe the impact of the exposome on acne and how photoprotection can improve outcomes. METHODS: A narrative review of the literature was carried out; searches with Google Scholar and Pubmed from January 1992 to November 2022 were performed. The keywords used were "acne," "sunscreens," "photoprotection," "cosmetics," "cosmeceuticals," "pathogenesis," "etiology," "exposome," "sunlight," "stress," "lack of sleep," "diet," "postinflammatory hyperpigmentation," "pollution," "exposome," "ultraviolet radiation," and "visible light." RESULTS: Environmental factors such as solar radiation, air pollution, tobacco consumption, psychological stress, diverse microorganisms, nutrition, among others, can trigger or worsen acne. Solar radiation can temporarily improve lesions. However, it can induce proinflammatory and profibrotic responses, and produce post-inflammatory hyperpigmentation and/or post-inflammatory erythema. While photoprotection is widely recommended to acne patients, only four relevant studies were found. Sunscreens can significantly improve symptomatology or enhance treatment and can prevent post-inflammatory hyperpigmentation. Furthermore, they can provide camouflage and improve quality of life. Based on acne pathogenesis, optimal sunscreens should have emollient, antioxidant and sebum controlling properties. CONCLUSIONS: The exposome and solar radiation can trigger or worsen acne. UV light can induce post-inflammatory hyperpigmentation/erythema, and can initiate flares. The use of specifically formulated sunscreens could enhance adherence to topical or systemic therapy, camouflage lesions (tinted sunscreens), decrease inflammation, and reduce the incidence of post-inflammatory hyperpigmentation/erythema.

Women Authorship Trends in the Highest-Impact Anesthesiology Journals from 2005 to 2021.

Background: Although women and men have matriculated into medical schools in similar proportions since the 1980s, recent data indicate that anesthesiology is lagging in gender equity, especially in academic leadership roles.1,2 As promotion in academic medicine is strongly influenced by publications, understanding whether a lack of women authorship is contributing to this gender gap is crucial.3,4 This article aims to assess how woman authorship trends have changed in the last 16 years, including during the COVID-19 pandemic. Materials and Methods: The five highest impact journals in anesthesia were identified as Journal of Clinical Anesthesia, British Journal of Anaesthesia, Anesthesiology, PAIN, and Regional Anesthesia & Pain Medicine. Number of total authors, including women, men, and unknown gender authors as well as incidence of woman first and/or last author, was documented from articles published in 2005, 2010, 2015, 2020, and 2021. Results: This analysis shows that women are gaining representation in anesthesia publications. Overall, there was a statistically significant increase in the total number of women authors and women first and last authorship. However, as of 2021, women still only represented ∼40% of total and first authors and ∼24% of last authors. In addition, increase in first/last woman authorship was not present in all journals when stratified. Conclusion: These journal differences may suggest the editorial evaluation process as a potential source of gender bias. There was a statistically significant relationship between women senior authors and articles with 50% or more women authors, indicating that woman mentorship is contributing to closing equity gap. These data present a starting point for further investigations into gender disparities within anesthesia to continue the forward progression for women in academic medicine.

Determination of the effect of iatrogenic blood contamination on lactate dehydrogenase and creatine kinase activity in canine cerebrospinal fluid.

BACKGROUND: Lactate dehydrogenase (LDH) and creatine kinase (CK) have differential tissue activity and isoenzyme profiles. LDH and CK exist as 5 and 3 isoenzymes, respectively, in both serum and cerebrospinal fluid (CSF). Studies have demonstrated that measuring LDH, CK, and their isoenzymes in CSF has diagnostic and prognostic values for dogs and people with neurologic disorders. OBJECTIVES: Iatrogenic blood contamination can distort the results of CSF analysis. The purpose of this study was to determine allowable thresholds of blood contamination (RBC/µL) for accurate measurement of LDH, CK, and their isoenzymes in canine CSF. METHODS: Venous blood and CSF were collected from healthy dogs. Total LDH and CK activity were measured spectrophotometrically. Isoenzyme profiles were determined using gel electrophoresis and densitometric scanning. All samples were analyzed within 6 hours of collection. A nonlinear mixed effects regression model was used to estimate the allowable thresholds of blood contamination for accurate measurement of LDH, CK, and their isoenzymes in canine CSF. RESULTS: The threshold of iatrogenic blood contamination for total LDH and total CK in healthy dogs are 6696 RBC/µL (95% CI 3879-11 187) and 5961 RBC/µL (95% CI 2939-12 085), respectively. LDH-1 is the most sensitive isoenzyme to iatrogenic blood contamination, while LDH-4 is the least sensitive. CONCLUSIONS: These results are important for the interpretation of LDH, CK, and their isoenzymes in canine CSF. Additionally, our methodology is translatable for determining thresholds of acceptable iatrogenic blood contamination in CSF for other diagnostic and prognostic biomarkers of neurologic disease.

Implementation of an Enhanced Recovery after Surgery Pathway to Reduce Inpatient Opioid Consumption after Cesarean Delivery.

OBJECTIVE: Opioid prescription after cesarean delivery is excessive and can lead to chronic opioid use disorder. We assessed the impact of an enhanced recovery after surgery (ERAS) pathway on inpatient opioid consumption after cesarean delivery. STUDY DESIGN: An ERAS pathway was implemented as a quality improvement initiative in December 2019. Preintervention (PRE) data were collected from March to May 2019 to assess baseline opioid consumption. Postintervention (POST) data were collected from January to March 2020. The primary outcome was inpatient postoperative opioid consumption in morphine milligram equivalents (MME). Secondary outcomes included the consumption of any opioids, postpartum length of stay, and opioid prescription at discharge. RESULTS: A total of 92 women were in the PRE group and 91 were in the POST group. Inpatient opioid consumption decreased by 87.3% from PRE to POST, from 124.7 (interquartile range [IQR]: 10-181.6) MME to 15.8 (IQR: 0-75) MME (p < 0.001). There was no difference in median postpartum length of stay (3.4 days PRE vs. 3.3 days POST; p = 0.12). The proportion of women who did not consume any opioids increased by 75.4% from PRE to POST (p = 0.02). The proportion of women discharged with an opioid prescription decreased by 25.6% from PRE to POST (p = 0.007), despite no formal change to prescribing practices. After adjustment for differences in race/ethnicity and gravidity, there was still a reduction in total inpatient opioid consumption (p < 0.001) and an increase in the proportion of women not consuming any opioids (adjusted relative risk (RR): 2.14, 95% confidence interval [CI]: 1.18-3.87), but the difference in rate of prescription of opioids at discharge was no longer statistically significant (adjusted RR: 0.70, 95% CI: 0.48-1.02). CONCLUSION: Adoption of an ERAS pathway for cesarean delivery resulted in a marked reduction in inpatient opioid consumption. Such a pathway can be implemented across institutions and may be a powerful tool in combating the opioid epidemic. KEY POINTS: · ERAS after cesarean reduces inpatient opioid consumption.. · ERAS after cesarean increases the proportion of women not consuming any opioids.. · This pathway can be feasibly adopted elsewhere..

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection.

Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy. Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2. Design, Setting, and Participants: This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads. Exposures: SARS-CoV-2 infection vs COVID-19 vaccination. Main Outcomes and Measures: IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines. Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination. Conclusions and Relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

Defining the versican interactome in lung health and disease.

The extracellular matrix (ECM) imparts critical mechanical and biochemical information to cells in the lungs. Proteoglycans are essential constituents of the ECM and play a crucial role in controlling numerous biological processes, including regulating cellular phenotype and function. Versican, a chondroitin sulfate proteoglycan required for embryonic development, is almost absent from mature, healthy lungs and is reexpressed and accumulates in acute and chronic lung disease. Studies using genetically engineered mice show that the versican-enriched matrix can be pro- or anti-inflammatory depending on the cellular source or disease process studied. The mechanisms whereby versican develops a contextual ECM remain largely unknown. The primary goal of this review is to provide an overview of the interaction of versican with its many binding partners, the "versican interactome," and how through these interactions, versican is an integrator of complex extracellular information. Hopefully, the information provided in this review will be used to develop future studies to determine how versican and its binding partners can develop contextual ECMs that control select biological processes. Although this review focuses on versican and the lungs, what is described can be extended to other proteoglycans, tissues, and organs.

Neighborhood Characteristics and Racial Disparities in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seropositivity in Pregnancy.

OBJECTIVE: To quantify the extent to which neighborhood characteristics contribute to racial and ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity in pregnancy. METHODS: This cohort study included pregnant patients who presented for childbirth at two hospitals in Philadelphia, Pennsylvania from April 13 to December 31, 2020. Seropositivity for SARS-CoV-2 was determined by measuring immunoglobulin G and immunoglobulin M antibodies by enzyme-linked immunosorbent assay in discarded maternal serum samples obtained for clinical purposes. Race and ethnicity were self-reported and abstracted from medical records. Patients' residential addresses were geocoded to obtain three Census tract variables: community deprivation, racial segregation (Index of Concentration at the Extremes), and crowding. Multivariable mixed effects logistic regression models and causal mediation analyses were used to quantify the extent to which neighborhood variables may explain racial and ethnic disparities in seropositivity. RESULTS: Among 5,991 pregnant patients, 562 (9.4%) were seropositive for SARS-CoV-2. Higher seropositivity rates were observed among Hispanic (19.3%, 104/538) and Black (14.0%, 373/2,658) patients, compared with Asian (3.2%, 13/406) patients, White (2.7%, 57/2,133) patients, and patients of another race or ethnicity (5.9%, 15/256) (P<.001). In adjusted models, per SD increase, deprivation (adjusted odds ratio [aOR] 1.16, 95% CI 1.02-1.32) and crowding (aOR 1.15, 95% CI 1.05-1.26) were associated with seropositivity, but segregation was not (aOR 0.90, 95% CI 0.78-1.04). Mediation analyses revealed that crowded housing may explain 6.7% (95% CI 2.0-14.7%) of the Hispanic-White disparity and that neighborhood deprivation may explain 10.2% (95% CI 0.5-21.1%) of the Black-White disparity. CONCLUSION: Neighborhood deprivation and crowding were associated with SARS-CoV-2 seropositivity in pregnancy in the prevaccination era and may partially explain high rates of SARS-CoV-2 seropositivity among Black and Hispanic patients. Investing in structural neighborhood improvements may reduce inequities in viral transmission.

Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in east occitania.

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation.