Placental pathology lesions: International Society for Ultrasound In Obstetrics And Gynecology vs. Society for Maternal-Fetal Medicine Fetal growth restriction definitions.

BACKGROUND: Research on the definition of fetal growth restriction has focused on predicting adverse perinatal outcomes. A significant limitation of this approach is that the individual outcomes of interest could be related to the condition and the treatment. Evaluation of outcomes that reflect the pathophysiology of fetal growth restriction may overcome this limitation. OBJECTIVE: To compare the diagnostic performance of the fetal growth restriction definitions established by the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine to predict placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome. STUDY DESIGN: In this retrospective cohort study of singleton pregnancies, the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine guidelines were used to identify pregnancies with fetal growth restriction and a corresponding control group. The primary outcome was the prediction of placental histopathological findings associated with placental insufficiency, defined as lesions associated with maternal vascular malperfusion. A composite adverse neonatal outcome (i.e., umbilical artery pH≤7.1, Apgar score at 5 minutes ≤4, neonatal intensive care unit admission, hypoglycemia, respiratory distress syndrome requiring mechanical ventilation, intrapartum fetal distress requiring expedited delivery, and perinatal death) was investigated as a secondary outcome. Sensitivity, specificity, positive and negative predictive values, and the areas under the receiver-operating-characteristics curves were determined for each fetal growth restriction definition. Logistic regression models were used to assess the association between each definition and the studied outcomes. A subgroup analysis of the diagnostic performance of both definitions stratifying the population in early and late fetal growth restriction was also performed. RESULTS: Both societies' definitions showed a similar diagnostic performance as well as a significant association with the primary (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 3.01 [95% confidence interval 2.42, 3.75]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.85 [95% confidence interval 2.31, 3.51]) and secondary outcomes (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 1.95 [95% confidence interval 1.56, 2.43]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.12 [95% confidence interval 1.70, 2.65]). Furthermore, both fetal growth restriction definitions had a limited discriminatory capacity for placental histopathological findings of maternal vascular malperfusion and the composite adverse neonatal outcome (area under the receiver-operating-characteristics curve International Society for Ultrasound in Obstetrics and Gynecology 0.63 [95% confidence interval 0.61, 0.65], 0.59 [95% confidence interval 0.56, 0.61]; area under the receiver-operating-characteristics Society for Maternal-Fetal Medicine 0.63 [95% confidence interval 0.61, 0.66], 0.60 [95% confidence interval 0.57, 0.62]). CONCLUSIONS: The International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine fetal growth restriction definitions have limited discriminatory capacity for placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome.

Uterus transplantation: A scoping review focused on obstetric outcomes.

BACKGROUND: Congenital uterine anomalies include a wide diversity of uterine malformations that can compromise reproductive potential. Uterus transplantation (UTx) proposes an innovative treatment for absolute uterine factor infertility; however, there is a lack of standardized protocols to guide clinical management among this population. OBJECTIVES: To describe recipient and donor characteristics and obstetric outcomes in patients undergoing UTx. SEARCH STRATEGY: We performed a literature search using the PubMed database to retrieve available scientific articles. We analyzed the references of included articles to assess additional articles that could be eligible to be included in the review. Likewise, we identified further studies using other methods, including Google Scholar. SELECTION CRITERIA: Titles and abstracts were screened in duplicate to select original reports with information available for the outcomes of interest. DATA COLLECTION AND ANALYSIS: This review assessed the advantages and disadvantages of the techniques used, patient characteristics, obstetric and non-obstetric complications, functional duration of the organ, and neonatal outcomes. MAIN RESULTS: Among the 36 reports included in this review we found 55 pregnancies and 38 live births following UTx and a higher success rate for in vivo uterine donations. The most common obstetric complications reported included miscarriage, pre-eclampsia, and gestational hypertension. The most common non-obstetric complications reported include episodes of rejection, acute kidney injury, anemia, and cholestasis. Living donors required a comprehensive preoperative workup, decreasing organ rejection, infection, and vascular complications. CONCLUSIONS: More studies are needed to standardize the UTx procedure and improve obstetric, fetal, and neonatal outcomes. Further understanding of which recipient and donor characteristics minimize complications will significantly decrease the risk of adverse outcomes.

A seasonal study on the microbiomes of Diploid vs. Triploid eastern oysters and their denitrification potential.

Oyster reefs are hotspots of denitrification mediated removal of dissolved nitrogen (N), however, information on their denitrifier microbiota is scarce. Furthermore, in oyster aquaculture, triploids are often preferred over diploids, yet again, microbiome differences between oyster ploidies are unknown. To address these knowledge gaps, farmed diploid and triploid oysters were collected over an annual growth cycle and analyzed using shotgun metagenomics and quantitative microbial elemental cycling (QMEC) techniques. Regardless of ploidy, Psychrobacter genus was abundant, with positive correlations found for genes of central metabolism, DNA metabolism, and carbohydrate metabolism. MAGs (metagenome-assembled genomes) yielded multiple Psychrobacter genomes harboring norB, narH, narI, and nirK denitrification genes, indicating their functional relevance within the eastern oysters. QMEC analysis indicated the predominance of carbon (C) and nitrogen (N) cycling genes, with no discernable patterns between ploidies. Among the N-cycling genes, the nosZII clade was overrepresented, suggesting its role in the eastern oyster's N removal processes.

Cumulative sum learning curve for cordocentesis among maternal-fetal medicine fellows in a low-cost simulation model.

OBJECTIVE: To determine the individual learning curves for cordocentesis in a low-cost simulator for maternal-fetal medicine (MFM) fellows. METHODS: This observational, descriptive, educational, and prospective study was performed from July through November 2022. After an introductory course based on a standardized technique for cordocentesis, each second-year MFM fellow who accepted to participate in the study performed this procedure using a low-cost simulation model, and experienced operators supervised the cordocenteses. Learning curves were then created using cumulative sum analysis (CUSUM). RESULTS: Seven second-year MFM fellows with no previous experience in cordocentesis accepted to participate in the study. A total of 2676 procedures were assessed. On average, residents performed 382 ± 70 procedures. The mean number of procedures to achieve proficiency was 369 ± 70, the overall success rate was 84.16%, and the corresponding failure rate was 15.84%. At the end of the study, all fellows were considered competent in cordocentesis. One fellow required 466 attempts to achieve competency, performing a total of 478 procedures, but the resident with the fewest attempts to reach competency required 219 procedures, completing 232 procedures. Some of the most frequent reasons for failed attempts included not reaching the indicated point for vascular access (20.99%) and being unable to retrieve the sample (69.10%). CONCLUSION: CUSUM analysis to assess learning curves, in addition to using low-cost simulation models, helped to appraise individualized learning, allowing an objective demonstration of competency for cordocentesis among MFM fellows.

Clinical Characteristics and Outcomes of Patients with Heart Failure of Hypertensive Etiology: Analysis of Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Arterial hypertension represents one of the main comorbidities observed in patients with heart failure (HF) and one of the main risk factors for its development. Despite this, studies assessing this hypertensive etiology are scarce in Latin America. Our objective was to analyze the prevalence of HF of hypertensive etiology and evaluate its prognosis in patients enrolled in the Colombian Heart Failure Registry (RECOLFACA by its Spanish acronym). METHODS: RECOLFACA recruited adult patients diagnosed with HF in 60 centers in Colombia between 2017 and 2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess factors associated with primary outcomes in patients with hypertensive HF. A p value <0.05 was considered significant. All statistical tests were two-tailed. RESULTS: Out of the total number of patients evaluated in RECOLFACA (n = 2,514), 804 had a diagnosis of HF with hypertensive etiology (31.9%). These patients were less frequently males and had a significantly older age and lower prevalence of comorbidities than those with HF of other etiologies. Additionally, patients with hypertensive HF had a higher prevalence of HF with preserved ejection fraction (HFpEF) (34.1% vs. 28.3%; p = 0.004). Finally, type 2 diabetes mellitus, chronic obstructive pulmonary disease diagnosis, and NYHA class IV were classified as independent mortality risk factors. CONCLUSIONS: Hypertensive HF represents about one-third of the total number of patients with HF in RECOLFACA. Compared with HF of other etiologies, it presents a differential clinical profile - older age and a higher prevalence of HFpEF. RECOLFACA has become a useful tool to characterize patients with HF in Colombia, with which it has been possible to carry out a more specific search and reach the diagnosis of this pathology in our population, and it has served as an example to stimulate registries of patients with HF in other countries in the region.

HERPUD1 governs tumor cell mitochondrial function via inositol 1,4,5-trisphosphate receptor-mediated calcium signaling.

The intricate relationship between calcium (Ca2+) homeostasis and mitochondrial function is crucial for cellular metabolic adaptation in tumor cells. Ca2+-initiated signaling maintains mitochondrial respiratory capacity and ATP synthesis, influencing critical cellular processes in cancer development. Previous studies by our group have shown that the homocysteine-inducible ER Protein with Ubiquitin-Like Domain 1 (HERPUD1) regulates inositol 1,4,5-trisphosphate receptor (ITPR3) levels and intracellular Ca2+ signals in tumor cells. This study explores the role of HERPUD1 in regulating mitochondrial function and tumor cell migration by controlling ITPR3-dependent Ca2+ signals. We found HERPUD1 levels correlated with mitochondrial function in tumor cells, with HERPUD1 deficiency leading to enhanced mitochondrial activity. HERPUD1 knockdown increased intracellular Ca2+ release and mitochondrial Ca2+ influx, which was prevented using the ITPR3 antagonist xestospongin C or the Ca2+ chelator BAPTA-AM. Furthermore, HERPUD1 expression reduced tumor cell migration by controlling ITPR3-mediated Ca2+ signals. HERPUD1-deficient cells exhibited increased migratory capacity, which was attenuated by treatment with xestospongin C or BAPTA-AM. Additionally, HERPUD1 deficiency led to reactive oxygen species-dependent activation of paxillin and FAK proteins, which are associated with enhanced cell migration. Our findings highlight the pivotal role of HERPUD1 in regulating mitochondrial function and cell migration by controlling intracellular Ca2+ signals mediated by ITPR3. Understanding the interplay between HERPUD1 and mitochondrial Ca2+ regulation provides insights into potential therapeutic targets for cancer treatment and other pathologies involving altered energy metabolism.

Whole blood viscoelastic testing profile and mortality in patients hospitalized with acute COVID-19 pneumonia: A systematic review and meta-analysis.

BACKGROUND: Several studies have evaluated the possible association between whole blood viscoelastic testing (VET) parameters in patients hospitalized for acute Coronavirus disease 2019 (COVID-19) pneumonia and mortality. A few studies found no significant differences between survivors and non-survivors, though other studies identified potential predictors of COVID-19-related mortality. We conducted a systematic review and meta-analysis of the literature to evaluate the possible association between standard thromboelastometry/graphy parameters and mortality in patients hospitalized for acute COVID-19 pneumonia. METHODS: Relevant studies were searched through MEDLINE, EMBASE, and Google Scholar from their inception until 15th June 2023. We aimed to identify any study including: i) adults admitted to intensive care units (ICU) or medicine wards (MW) for acute COVID-19 pneumonia; ii) viscoelastic testing; iii) mortality. RESULTS: We included 13 studies: nine prospective and four retrospective, 231 (30.4 %) non-survivors and 528 (69.6 %) survivors. Mortality rates ranged from 12.8 % to 67.5 %. The studies using the TEG apparatus found a significant difference in K time in the Kaolin test among survivors vs. non-survivors (mean difference [MD] 0.20, 95 % confidence interval [CI] 0.12, 0.28, I2 0%). The studies using the rotational thromboelastometry apparatus found a significant difference in CT-INTEM (MD -17.14, 95 % CI -29.23, -5.06, I2 0%) and LI60-EXTEM (MD -1.00, 95 % CI -1.00, -1.00, I2 0%) assays among survivors vs. non-survivors. CONCLUSION: We identified no specific hypercoagulable or hypocoagulable profile associated with mortality in patients with COVID-19-related pneumonia. Large prospective studies are needed to explore the possible prognostic role of VET in this subset of patients.

Abdominal circumference growth velocity as a predictor of adverse perinatal outcomes in small-for-gestational-age fetuses.

OBJECTIVE: To assess the predictive value of abdominal circumference growth velocity (ACGV) between the second and third trimesters to predict adverse perinatal outcomes in a cohort of small-for-gestational-age fetuses without evidence of placental insufficiency (i.e. fetal growth restriction). MATERIAL AND METHODS: This is a single-center retrospective cohort study of all singleton pregnancies with small-for-gestational-age fetuses diagnosed and delivered at a quaternary institution. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between abnormal ACGV (i.e. ≤10th centile) and adverse perinatal outcomes defined as a composite outcome (i.e. umbilical artery pH <7.1, 5-min Apgar score <7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). Furthermore, the area under the receiver-operating characteristic curve (AUC) of three logistic regression models based on estimated fetal weight and ACGV for predicting the composite outcome is also reported. RESULTS: A total of 154 pregnancies were included for analysis. The median birthweight for the cohort was 2,437 g (interquartile range [IQR] 2280, 2635). Overall, the primary composite outcome was relatively common (29.2%). In addition, there was a significant association between abnormal ACGV and adverse perinatal outcomes (OR 3.37, 95% CI 1.60, 7.13; adjusted OR 4.30, 95% CI 1.77, 10.49). Likewise, the AUC for the ACGV was marginally higher (0.64) than the estimated fetal weight (0.54) and ACGV + estimated fetal weight (0.54). Still, no significant difference was detected between the curves (p = 0.297). CONCLUSIONS: Our results suggest that an ACGV below the 10th centile is a risk factor for adverse perinatal outcomes among small-for-gestational-age fetuses.

Intended delivery mode and neonatal outcomes in pregnancies with fetal growth restriction.

Objective: To compare neonatal outcomes in pregnancies with fetal growth restriction (FGR) by intended delivery mode.Methods: This is a retrospective cohort study of singleton pregnancies with FGR that were delivered ≥34.0 weeks gestation. Neonatal outcomes were compared according to the intended delivery mode, which the attending obstetrician determined. Of note, none of the subjects had a contraindication to labor. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between intended delivery mode and neonatal morbidity defined as a composite outcome (i.e. umbilical artery pH ≤7.1, 5-min Apgar score ≤7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). A sensitivity analysis excluded intrapartum fetal distress requiring emergency cesarean delivery from the composite outcome since only patients with spontaneous labor or labor induction could meet this criterion. Potential confounders in the adjusted effects models included maternal age, body mass index, hypertensive disorders, diabetes, FGR type (i.e. early or late), and oligohydramnios.Results: Seventy-two (34%) patients had an elective cesarean delivery, 73 (34%) had spontaneous labor and were expected to deliver vaginally, and 67 (32%) underwent labor induction. The composite outcome was observed in 65.3%, 89%, and 88.1% of the groups mentioned above, respectively (p < 0.001). Among patients with spontaneous labor and those scheduled for labor induction, 63% and 47.8% required an emergency cesarean delivery for intrapartum fetal distress. Compared to elective cesarean delivery, spontaneous labor (OR 4.32 [95% CI 1.79, 10.42], p = 0.001; aOR 4.85 [95% CI 1.85, 12.66], p = 0.001), and labor induction (OR 3.92 [95% CI 1.62, 9.49] p = 0.002; aOR 5.29 [95% CI 2.01, 13.87], p = 0.001) had higher odds of adverse neonatal outcomes.Conclusion: In this cohort of FGR, delivering at ≥34 weeks of gestation, pregnancies with spontaneous labor, and those that underwent labor induction had higher odds of neonatal morbidity than elective cesarean delivery.

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine.

BACKGROUND: The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method. METHODS: A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression. RESULTS: A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55-31.56) with a DPE technique and 45.25 mg (90% CI, 42.80-52.03) with an EPL technique. CONCLUSIONS: Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.

Characterization of Patients With Heart Failure of Chagas Etiology in Colombia: An Analysis Based on the Colombian Registry of Heart Failure (RECOLFACA).

Chronic Chagas cardiomyopathy (CCM) represents a relevant origin of Heart Failure (HF) in countries where the disease is endemic. CCM exhibits distinct myocardial involvement and is associated with a poorer prognosis compared to different HF etiologies. The aim is to explain the features and prognosis of individuals with HF resultant to CCM registered in the Colombian Registry of Heart Failure (RECOLFACA). RECOLFACA registry enrolled 2528 adult patients with HF. A comparison was made between patients diagnosed with CCM and those diagnosed with other etiologies of HF. Eighty-eight patients (3.5%) present CCM diagnosis. The individuals diagnosed with both HF and CCM were notably younger in age, had less comorbidities, poorer functional class, and significantly inferior ejection fraction. Finally, the presence of CCM diagnosis was linked to a substantially elevated mortality risk throughout the follow-up period (HR 2.01; 95% CI, 1.01-4.00) according to a multivariate model adjusted. CCM represents an important etiology of HF in Colombia, drawing attention to a distinct clinical profile and a higher risk of mortality compared to other HF etiologies.

Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1.

Introduction: Cardiovascular diseases, especially metabolic-related disorders, are progressively growing worldwide due to high-fat-containing foods, which promote a deleterious response at the cellular level, termed lipotoxicity, or lipotoxic stress. At the cardiac level, saturated fatty acids have been directly associated with cardiomyocyte lipotoxicity through various pathological mechanisms involving mitochondrial dysfunction, oxidative stress, and ceramide production, among others. However, integrative regulators connecting saturated fatty acid-derived lipotoxic stress to mitochondrial and cardiomyocyte dysfunction remain elusive. Methods: Here, we worked with a cardiomyocyte lipotoxicity model, which uses the saturated fatty acid myristate, which promotes cardiomyocyte hypertrophy and insulin desensitization. Results: Using this model, we detected an increase in the mitochondrial E3 ubiquitin ligase, MUL1, a mitochondrial protein involved in the regulation of growth factor signaling, cell death, and, notably, mitochondrial dynamics. In this context, myristate increased MUL1 levels and induced mitochondrial fragmentation, associated with the decrease of the mitochondrial fusion protein MFN2, and with the increase of the mitochondrial fission protein DRP1, two targets of MUL1. Silencing of MUL1 prevented myristate-induced mitochondrial fragmentation and cardiomyocyte hypertrophy. Discussion: These data establish a novel connection between cardiomyocytes and lipotoxic stress, characterized by hypertrophy and fragmentation of the mitochondrial network, and an increase of the mitochondrial E3 ubiquitin ligase MUL1.

Comorbidity profile and outcomes in patients with chronic heart failure in a Latin American country: Insights from the Colombian heart failure registry (RECOLFACA).

BACKGROUND: Heart failure (HF) is usually accompanied by cardiovascular and non-cardiovascular comorbidities, which may significantly impact its prognosis. In this study we aimed to characterize the comorbidity profile and its impact in mortality in patients with HF diagnosis from the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess the impact of the comorbidities in mortality. A p-value of <0.05 was considered significant. RESULTS: From the total 2528 patients included in the registry, 2514 patients (58% males, mean age 68 years) had information regarding comorbidity diagnoses. 2321 patients (92.3%) reported at least one comorbidity. Arterial hypertension was the most frequent individual diagnosis (72%; n = 1811), followed by anemia (30.1%, n = 726). The most frequently observed coexisting comorbidities were coronary disease (CHD) with dyslipidemia, and chronic kidney disease (CKD) with type 2 Diabetes Mellitus (T2DM). Different patterns of comorbidity coexistence were observed when comparing HF patients by sex and left-ventricular ejection fraction (LVEF) classification. The only comorbidities that were significantly associated with mortality after multivariate adjustment were T2DM (HR 1.45. 95% CI 1.01-2.12), anemia (HR 1.48. 95% CI 1.02-2.16), and CHD (HR 1.59. 95% CI 1.09-2.33). CONCLUSION: Multiple comorbidities were frequently observed in the patients from the RECOLFACA. T2DM, anemia and CHD were significantly associated with a higher risk of mortality, highlighting the importance of promoting an optimal follow-up and control of these conditions.

Low-dose aspirin use in the first trimester of pregnancy and odds of congenital anomalies: A meta-analysis of randomized controlled trials.

BACKGROUND: Daily low-dose aspirin (LDA) is recommended in high-risk pregnancies. However, its safety profile in the first trimester has not been well documented. OBJECTIVES: To determine if LDA exposure during the first trimester of pregnancy is associated with higher odds of congenital structural anomalies. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were systematically searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) that assigned participants to LDA (≤150 mg) or placebo/no intervention at less than 14 weeks of pregnancy were eligible. DATA COLLECTION AND ANALYSIS: Random-effects models were performed using the inverse-variance method to calculate pooled effect sizes. Quality of evidence was appraised according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. MAIN RESULTS: Eight RCTs that included 7564 participants assigned to receive daily LDA and 7670 participants that served as controls were analyzed. Low-certainty evidence showed no significant difference in the odds of congenital anomalies (odds ratio 0.87, 95% confidence interval 0.62-1.23, I2  = 0%). CONCLUSIONS: In this meta-analysis, there is no evidence to suggest safety concerns regarding LDA teratogenicity. However, given the overall low quality of evidence, further research (e.g. individual participant data meta-analysis) is needed to confirm LDA safety profile.

Continuing professional development challenges in a rural setting: A mixed-methods study.

INTRODUCTION: Health professionals in rural settings encounter a wide range of medical conditions requiring broad knowledge for their clinical practice. This creates the need for ongoing continuing professional development (CPD). In this study, we explored the barriers that health professionals in a rural healthcare context faced participating in CPD activities and their preferences regarding educational strategies to overcome these challenges. METHODS: This mixed-methods (exploratory sequential) study in a community hospital in rural Mexico includes 22 interviews, 3 focus groups, 40 observational hours, and a questionnaire of healthcare staff. RESULTS: Despite low engagement with CPD activities (67% not motivated), all participants expressed interest and acknowledged the importance of learning for their practice. Barriers to participating include a disparity between strategies used (lecture-based) and their desire for practical learning, institutional barriers (poor leadership engagement, procedural flaws, and lack of resources), and collaboration barriers (adverse interprofessional education environment, ineffective teamwork, and poor communication). Additional barriers identified were inconvenient scheduling of sessions (75%), inadequate classrooms (65%), high workload (60%), ineffective speakers (60%), and boring sessions (55%). Participants' preferred learning strategies highlighted activities relevant to their daily clinical activities (practical workshops, simulations, and case analysis). The questionnaire had an 18% response rate. DISCUSSION: The barriers to CPD in this rural setting are multifactorial and diverse. A strong interest to engage in context-specific active learning strategies highlighted the need for leadership to prioritize interprofessional education, teamwork, and communication to enhance CPD and patient care. These results could inform efforts to strengthen CPD in other rural contexts.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Perceptions and Attitudes toward COVID-19 Vaccination among Pregnant and Postpartum Individuals.

OBJECTIVE: This study aimed to characterize attitudes toward novel coronavirus disease 2019 (COVID-19) vaccination and to evaluate factors associated with vaccine uptake among pregnant individuals. STUDY DESIGN: An anonymous survey was distributed to a convenience sample of pregnant individuals receiving prenatal care at two large urban academic hospitals in a single health care network in Massachusetts. Individual demographic variables were included in the survey along with questions assessing attitudes toward COVID-19 and vaccination in pregnancy. Data were analyzed using parametric or nonparametric tests when appropriate, and associated odds ratios (OR) were calculated via univariable logistic regression. RESULTS: There were 684 surveys distributed, and 477 pregnant and postpartum individuals completed the survey, for a response rate of 69.7%. Overall, 233 (49.3%) had received or were scheduled to receive a COVID-19 vaccine. Age, White race, non-Hispanic or Latinx ethnicity, working from home, and typical receipt of the influenza vaccine were associated with COVID-19 vaccination. Further, 276 respondents (58.4%) reported that their provider recommended the COVID-19 vaccine in pregnancy; these participants were more likely to have received a vaccine (OR = 5.82, 95% confidence interval [CI]: 3.68-9.26, p < 0.005). Vaccinated individuals were less likely to be worried about the effects of the vaccine on themselves (OR = 0.18, 95% CI: 0.12-0.27, p < 0.005) or their developing babies (OR = 0.17, 95% CI: 0.11-0.26, p < 0.005). Unvaccinated individuals were less likely to report that it is easy to schedule a COVID-19 vaccine (OR = 0.56, 95% CI: 0.34-0.93, p = 0.02), to travel to receive a vaccine (OR = 0.19, 95% CI: 0.10-0.36, p < 0.005), and to miss work to receive a vaccine (OR = 0.30, 95% CI: 0.18-0.48, p < 0.005). CONCLUSION: Strategies are needed to improve patient education regarding vaccine side effects and safety in pregnancy. Policy changes should focus on making it feasible for patients to schedule a vaccine and miss work without loss of pay to get vaccinated. KEY POINTS: · There were racial and ethnic disparities in COVID-19 vaccination.. · Unvaccinated respondents were more likely to be concerned about vaccine effects for themselves or their growing babies.. · Unvaccinated respondents cited work and scheduling-related barriers to vaccination, indicating areas for advocacy..