Venous Thromboembolism Prophylaxis Should Be Recommended for Antepartum Admissions and Cesarean Delivery if Age and Body Mass Index are Greater Than 35.

OBJECTIVE: Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. Current expanded treatment recommendations result in the inclusion of a large percentage of the obstetric population, which has limited their adoption. The purpose of this study was to identify a population at high risk for VTE, with minimal impact on the number of patients that would qualify for expanded treatment. STUDY DESIGN: We performed a retrospective analysis of a large obstetric population. International Classification of Diseases, 10th Revsion (ICD-10) codes for VTE were used to identify patients presenting for obstetric or postpartum (PP) care from January 2016 to March 2018. The review focused on high-risk factors (history of VTE or high-risk thrombophilia), antepartum hospital admissions that were >72 hours in the previous 30 days, use of sequential compression devices, body mass index (BMI; kg/m2), age, and mode of delivery. Pharmacologic treatment efficacy was set at 90, 75, or 50%. RESULTS: During the 27-month review period, there were 120,235 deliveries and 93 had a VTE event in the index pregnancy or within 4 weeks PP (7.7/10,000 births). A history of VTE or high-risk thrombophilia was seen in 25.8% of cases. Antepartum admission was noted in 40.9%, and the combination of cesarean delivery (CD) with age and BMI ≥35 (Age + BMI + CD) was noted in 17.3% of PP cases. Targeting these latter two groups for VTE prophylaxis with a 75% efficacy suggests that 34% of the VTE events would likely have been prevented while increasing the total population treated by approximately 2%. CONCLUSION: Expanding pharmacologic prophylactical coverage to include an antepartum admission of >72 hours and those with Age + BMI + CD would result in about a one-third reduction in total VTE events with about 2% requiring treatment. These data support some of the suggested recommendations for expanded pharmacological deep venous thrombosis prophylaxis. KEY POINTS: · CD, and BMI and age >35 are high-risk factors for VTE.. · Antepartum admission >72 hours is a high-risk factor for VTE.. · Targeting antepartum admissions, CD, and BMI and age >35 would reduce VTE events by about 33%..

E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers.

The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4-21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12-18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways.

The ENGAGE study: evaluation of a conversational virtual agent that provides tailored pre-test genetic education to cancer patients.

PURPOSE: Novel approaches are needed to ensure all patients with cancer have access to quality genetic education before genetic testing to enable informed treatment decisions. The purpose of this study was to test the use of an artificial intelligence (AI) intervention for the delivery of genetic education by non-genetic providers to patients with cancer undergoing active treatment. METHODS: A conversational AI-based application was developed on the HealthFAX platform to provide tailored genetic education to patients with cancer and tested at Johns Hopkins Hospital between April 2021 and Feb 2022. Patients' responses around the adoption, use, and experience of the AI application were assessed. RESULTS: Out of 64 individuals who consented to the study, 51 accessed the tool. The responding participants had a mean age of 61 years (ranging from 30-90 years) with 39 individuals undergoing active treatment for breast cancer and 12 for advanced prostate cancer. All patients chose to complete the tool at home. The median time between study enrollment and AI application initiation was 1 day, and the median time to complete the application was 24 min. All participants in their survey responses felt that the tool was secure, easy to use, liked the convenience of viewing it at home, and felt it provided valuable information. Eighteen percent of participants viewed the application with a family member. Ninety-eight percent of the participants completed their genetic education prior to receiving their test results. In 16%, a pathogenic variant was identified. CONCLUSIONS: The 51 patients who adopted the AI application were highly satisfied with its usability and convenience. Our results support the continued evaluation of this cost-effective AI application in a large-scale study. IMPLICATIONS FOR CANCER SURVIVORS: Tailored pre-test genetic education can be successfully delivered to patients with cancer undergoing active treatment via an AI application at their convenience.

Polycaprolactone-based scaffolds for guided tissue regeneration in periodontal therapy: A systematic review.

BACKGROUND: Polycaprolactone (PCL) is a highly recognized synthetic polymer for its biocompatibility, ease of fabrication and mechanical strength in bone tissue engineering. Its applications have extended broadly, including regeneration of oral and maxillofacial lost tissues. Its usefulness has brought attention of researchers to regenerate periodontal lost tissues, including alveolar bone, periodontal ligament and cementum. The aim of this systematic review was to obtain an updated analysis of the contribution of PCL-based scaffolds in the alveolar bone regeneration process. METHODS: This review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews. A computerized search of the PubMed, EBSCO, Scielo and Web of Science databases was performed, restricting literature search to published studies in English or Spanish between January 2002 and March 2023. Database search returned 248 studies which were screened based on title, author names and publication dates. RESULTS: Data from 17 studies were reviewed and tabulated. All studies combined PCL with other biomaterials (such as Alginate, hydroxyapatite, bioactive glass, poly (lactic-co-glycolic acid)), growth factors (BMP-2, rhCEMP1), and/or mesenchymal stromal cells (adipose-derived, bone marrow, periodontal ligament or gingiva mesenchymal stromal cells). PCL scaffolds showed higher cell viability and osteoinductive potential when combined with bioactive agents. Complementary, its degradation rates were affected by the addition or exposure to specific substances, such as: Dopamine, Cerium Oxide, PLGA and hydrogen peroxide. CONCLUSIONS: PCL is an effective biomaterial for alveolar bone regeneration in periodontally affected teeth. It could be part of a new generation of biomaterials with improved regenerative potential.

Osteoinductive Electrospun Scaffold Based on PCL-Col as a Regenerative Therapy for Peri-Implantitis.

Peri-implantitis is a serious condition affecting dental implants that can lead to implant failure and loss of osteointegration if is not diagnosed and treated promptly. Therefore, the development of new materials and approaches to treat this condition is of great interest. In this study, we aimed to develop an electrospun scaffold composed of polycaprolactone (PCL) microfibers loaded with cholecalciferol (Col), which has been shown to promote bone tissue regeneration. The physical and chemical properties of the scaffold were characterized, and its ability to support the attachment and proliferation of MG-63 osteoblast-like cells was evaluated. Our results showed that the electrospun PCL-Col scaffold had a highly porous structure and good mechanical properties. The resulting scaffolds had an average fiber diameter of 2-9 µm and high elongation at break (near six-fold under dry conditions) and elasticity (Young modulus between 0.9 and 9 MPa under dry conditions). Furthermore, the Col-loaded scaffold was found to decrease cell proliferation when the Col content in the scaffolds increased. However, cytotoxicity analysis proved that the PCL scaffold on its own releases more lactate dehydrogenase into the medium than the scaffold containing Col at lower concentrations (PCL-Col A, PCL-Col B, and PCL-Col C). Additionally, the Col-loaded scaffold was shown to effectively promote the expression of alkaline phosphatase and additionally increase the calcium fixation in MG-63 cells. Our findings suggest that the electrospun membrane loaded with Col can potentially treat peri-implantitis by promoting bone formation. However, further studies are needed to assess the efficacy and safety of this membrane in vivo.

A Systemwide Postpartum Inpatient Maternal Mental Health Education and Screening Program.

OBJECTIVE: To expand a hospital system's maternal mental health program to standardize screening for perinatal mood and anxiety disorders. DESIGN: Quality improvement initiative using a continuous Plan-Do-Study-Act (PDSA) cycle. SETTING/LOCAL PROBLEM: In a hospital system consisting of 66 maternity care centers across the United States, there was significant variation in maternal mental health screening, referral, and education practices. The COVID-19 pandemic and increasing rates of severe maternal morbidity further elevated system-level concern about the quality of maternal mental health care being provided. PARTICIPANTS: Perinatal nurses. METHODS: An "all-or-none" bundle methodology was used to measure adherence to a system standard for maternal mental health screening, referral, and education. INTERVENTIONS: A toolkit was designed internally to support streamlined implementation and ensure standardization for screening, referral, and education. This comprehensive toolkit includes screening forms, a referral algorithm, staff education, patient education literature, and a community resource list template. Training on how to use the toolkit was provided to nurses, chaplains, and social workers. RESULTS: The initial system bundle adherence rate was 76% (2017) in the first year of the program. The following year, the bundle adherence rate increased to 97% (2018). Despite the disruption caused by the COVID-19 pandemic, this mental health initiative has maintained an overall adherence rate of 92% (2020-2022). CONCLUSION: This nurse-led quality improvement initiative has been successfully implemented across a geographically and demographically diverse hospital system. The initial and sustained high rates of adherence with the system standard for screening, referral, and education illustrate perinatal nurses' commitment to the delivery of high-quality maternal mental health care in the acute care setting.

Atraumatic Splenic Rupture due to Chronic Myelomonocytic Leukemia Treated with Partial Splenic Artery Embolization.

Splenic rupture can be categorized into two groups: traumatic and atraumatic. Traumatic rupture is frequently associated with blunt abdominal trauma, while atraumatic splenic rupture (ASR) is more uncommon and has been associated with both benign and malignant hematological disorders. In general, most cases of splenic rupture are managed with splenectomy, which carries significant mortality and morbidity; more recently, splenic artery embolization (SAE) has become a mainstay of management particularly after traumatic rupture. We describe a patient with chronic myelomonocytic leukemia (CMML) who presented to the emergency department for acute abdominal pain and was found to have an ASR. He underwent partial SAE, with postoperative complications of leukocytosis and tumor lysis syndrome (TLS) requiring rasburicase and allopurinol. On follow-up in clinic 2 months post-discharge, the patient was doing well on hydroxyurea, without need for further intervention at that time. In patients with hematologic malignancies presenting with abdominal pain and splenomegaly, it is important to consider ASR as a rare, but possible complication. To our knowledge, this is the only reported patient treated with SAE in the context of ASR from CMML, demonstrating that SAE can be an effective nonoperative strategy for treatment of CMML-associated ASR. This case report also highlights postoperative complications and management in this patient population, specifically a profound leukocytosis and TLS, for which close monitoring should be performed.

Evolution and dispersal of snakes across the Cretaceous-Paleogene mass extinction.

Mass extinctions have repeatedly shaped global biodiversity. The Cretaceous-Paleogene (K-Pg) mass extinction caused the demise of numerous vertebrate groups, and its aftermath saw the rapid diversification of surviving mammals, birds, frogs, and teleost fishes. However, the effects of the K-Pg extinction on the evolution of snakes-a major clade of predators comprising over 3,700 living species-remains poorly understood. Here, we combine an extensive molecular dataset with phylogenetically and stratigraphically constrained fossil calibrations to infer an evolutionary timescale for Serpentes. We reveal a potential diversification among crown snakes associated with the K-Pg mass extinction, led by the successful colonisation of Asia by the major extant clade Afrophidia. Vertebral morphometrics suggest increasing morphological specialisation among marine snakes through the Paleogene. The dispersal patterns of snakes following the K-Pg underscore the importance of this mass extinction event in shaping Earth's extant vertebrate faunas.

Radiation recall dermatitis following letrozole administration in patient with a remote history of radiation therapy.

We report the case of letrozole-induced radiation recall dermatitis (RRD) in a patient with a remote history of radiation therapy. There is only one previously known case of RRD triggered by letrozole in a patient with a recent (<3 month) history of radiation. Previously, only four other cases of aromatase-inhibitor-induced RRD have been reported. This case is significant for cancer care teams considering personalized treatments. In addition, improved long-term outcomes in cancer patients may lead to increases in and underdiagnoses of RRD. Likewise, RRD is patient specific, exacerbating health concerns, and can be difficult to recognize without proper awareness, documentation, and classification of triggering drugs. The authors hope to address these issues in this report.

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

The effect of 1-day multidisciplinary clinic on breast cancer treatment.

PURPOSE: A delay in breast cancer treatment is associated with inferior survival outcomes; however, no clear guidelines exist defining the appropriate time frame from diagnosis to definitive treatment of breast cancer. A multidisciplinary approach for breast cancer treatment can minimize the time from diagnosis to first treatment. We hypothesized single-day multidisciplinary clinic (MDC) may accelerate the time to first treatment on complex breast cancer cases at our institution. METHODS: We identified patients who were treated at Johns Hopkins for stage II or III breast cancer, who were at least 18 years of age, and were seen in a new single-day MDC with coordination between two or three specialties or by specialists from varying disciplines on different days (IDC). Patients who initiated treatment between May 2015 (initiation of MDC clinic) and December 2017 were included in our study. RESULTS: A total of 296 patient records were reviewed independently. The mean (SD) patient age was 55 (13) years. The median time to first neoadjuvant chemotherapy (NACT) was significantly reduced for patients seen in the MDC (12.7 days), compared to those seen at the IDC (24.4 days, logrank p < 0.001). The median time to definitive surgery was similar between groups (31 and 32 days for the MDC and IDC cohorts, respectively). CONCLUSIONS: A single-day MDC visit is associated with a reduced time from diagnosis to NACT. Further studies are needed to determine if a shorter interval can improve the management and the outcome of complex breast cancer cases.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.

Preservación alveolar post extracción en zona estética: decisiones clinicas predecibles en sitio severamente afectado / Alveolar ridge preservation in the esthesic zone: predictable decisions in a severly affected site

INTRODUCCIÓN: La valoración particular de sitios severamente comprometidos, involucra considerar los tiempos necesarios de cicatrización, así como evidencia actual en términos de biomateriales y técnicas quirúrgicas con el fin de lograr un tratamiento exitoso. MATERIAL Y MÉTODO: Paciente sexo femenino, 28 años, asiste por dolor e infección en diente 2.1 al Postítulo de Periodoncia UDD. Se observa defecto extenso y lesión que compromete tanto las tablas óseas vestibular como palatina. El tratamiento consistió en: exodoncia y regeneración ósea, instalación del implante 6 meses después de la exodoncia y cirugía de conexión 7 meses después más injerto de tejidos blandos. RESULTADOS: El tratamiento de defectos combinados (tejidos duros y blandos), asociados a procesos infecciosos de larga data, mediante rehabilitación implanto soportada puede ser muy predecible y exitoso en la medida que se respeten los tiempos de regeneración de diferentes estructuras.

INTRODUCTION: The specific assessment of a severely compromised sites involves: the consideration of healing time according to the different kinds of tissues involved and the knowledge of the evidence available concerning biomaterials and surgical techniques. MATERIAL AND METHODS: Female patient attends the postgraduate school of periodontics, UDD University in Santiago de Chile, because of pain and chronic infection compromising tooth 2.1. At clinical evaluation, the site has an extensive defect, with active fistula that compromises the buccal and palatal bone plates. The treatment consisted of exodontia and guided bone regeneration, implantation six months after initial exodontia and abutment connection surgery seven months after implant insertion. RESULTS: the treatment of combined defects associated with a long-standing infectious process can be very predictable and successful, only if the measures of time and tissue handling are considered and applied.

Formaldehyde, Epigenetics, and Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia. The accumulation of ß-amyloid plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau protein are two hallmarks of AD. The ß-amyloid and tau proteins have been at the center of AD research and drug development for decades. However, most of the clinical trials targeting ß-amyloid have failed. Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis and perhaps the tau hypothesis as well. Multilevel complex interactions between genetic, epigenetic, and environmental factors contribute to the occurrence and progression of AD. Formaldehyde (FA) is a widespread environmental organic pollutant. It is also an endogenous metabolite in the human body. Recent studies suggest that elevation of FA in the body by endogenous and/or exogenous exposure may play important roles in AD development. We have demonstrated that FA reduces lysine acetylation of cytosolic histones, thereby compromising chromatin assembly and resulting in the loss of histone content in chromatin, a conserved feature of aging from yeast to humans. Aging is an important factor for AD progression. Therefore, FA-induced inhibition of chromatin assembly and the loss of histones may contribute to AD initiation and/or development. This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and the involvement of FA in AD development. The exploration of chemical exposures as contributing factors to AD may provide new insights into AD mechanisms and could identify potential novel therapeutic targets.

A Standardized Approach for Category II Fetal Heart Rate with Significant Decelerations: Maternal and Neonatal Outcomes.

OBJECTIVE: To determine if a standardized intervention process for Category II fetal heart rates (FHRs) with significant decels (SigDecels) would improve neonatal outcome and to determine the impact on mode of delivery rates. STUDY DESIGN: Patients with Category II FHRs from six hospitals were prospectively managed using a standardized approach based on the presence of recurrent SigDecels. Maternal and neonatal outcomes were compared between pre- (6 months) and post-(11 months) implementation. Neonatal outcomes were: 5-minute APGAR scores of <7, <5, <3, and severe unexpected newborn complications (UNC). Maternal outcomes included primary cesarean and operative vaginal birth rates of eligible deliveries. RESULTS: Post implementation there were 8,515 eligible deliveries, 3,799 (44.6%) were screened, and 361 (9.5%) met criteria for recurrent SigDecels. Compliance with the algorithm was 97.8%. The algorithm recommended delivery in 68.0% of cases. Relative to pre-implementation, 5-minute APGAR score of <7 were reduced by 24.6% (p < 0.05) and severe UNC by -26.6%, p = < .05. The rate of primary cesarean decreased (19.8 vs 18.3%, p < 0.05), while there were nonsignificant increases in vaginal (74.6 vs 75.8%, p = 0.13) and operative vaginal births (5.7 vs 5.9%, p = 0.6). CONCLUSION: Standardized management of recurrent SigDecels reduced the rate of 5-minute APGAR scores of < 7 and severe UNC.