Importance of Appropriate Coagulation Evaluation in a Peripartum Patient with a Complex Medical History

Background Peripartum patients have physiologic changes affecting coagulation. Patients with complex disease states may have additional coagulopathy risks and have a higher risk of bleeding complications. It is important during the prenatal work-up to evaluate coagulation appropriately to prevent the risk of bleeding events such as postpartum hemorrhage. Case Description We present a 34-year-old G4P0121 patient at 37 weeks gestation, with a history of immune thrombocytopenia (ITP), hepatitis C, and repaired Tetralogy of Fallot. Her pregnancy was complicated by coagulopathy, necessitating medical optimization prior to delivery. On admission, the patient demonstrated thrombocytopenia, hypofibrinogenemia, increased von Willebrand activity with unremarkable multimer studies, and abnormal TEG results, prompting the initiation of Intravenous immunoglobulin (IVIG), prednisone, vitamin K, cryoprecipitate, and platelet transfusions in preparation of delivery. Despite medical management she suffered post-partum hemorrhage which was managed with uterotonic and antifibrinolytic agents. The remainder of the postpartum course was uncomplicated. Clinical Significance The patient’s complex medical background portends multiple effectors of her coagulation status. Pregnant patients have dilutional anemia, and increased prothrombotic factors, Factors V, VII, VIII, IX, XII, and fibrinogen, and positive D-dimer results. Patients with liver disease are affected by decreased and dysregulated coagulation factors and prothrombotic factors. Congenital heart disease can lead to high velocity gradients across abnormal heart valves leading to increased sheering stress. This leads to nonfunctional von Willibrand Factor (vWF) multimers that can’t function as effectively causing impaired platelet aggregation and adhesion. Conclusions A multifactorial approach with early, comprehensive coagulation workup and attention to less common differentials in high-risk PPH patients can provide targeted coagulation management before labor, thus significantly reducing the risk of bleeding complications

Optimization and Protection of Kidney Health in Liver Transplant Recipients: Intra- and Postoperative Approaches

Postoperative acute kidney injury after liver transplant (LT) has long-term implications for kidney health. LT recipients are at risk of acute kidney injury due to a number of factors related to the donor liver, intraoperative factors including surgical technique, as well as recipient factors, such as pre-LT kidney function and postoperative complications. This review discusses these factors in detail and their impact on posttransplant kidney function. Long-term risk factors such as calcineurin inhibitors have also been discussed. Additionally, the impact of liver allocation policies on pre- and post-LT kidney health is discussed

Belatacept Maintenance Immunosuppression for Calcineurin Inhibitor Sparing or Avoidance in Pancreas Transplant Recipients With Progressive Renal or Renal Allograft Dysfunction

Belatacept may be used to spare or replace calcineurin inhibitors (CNI) to preserve renal function. Use in pancreas transplant (PTx) is limited by increased risk of pancreas rejection. This retrospective analysis included all PTxs performed between 2004 and 2023. A 1:2 case/control analysis was performed to identify predictors of belatacept use and compare allograft and patient survival. Of 731 PTxs, 21 (3%) started belatacept (eight simultaneous pancreas and kidney (SPK), three pancreas after kidney (PAK), and 10 pancreas transplant alone (PTA). At 1 year, Δ estimated glomerular filtration rate (eGFR) was +7% SPK, -15% PAK, and +32% PTA. Case-control analysis found no demographic predictors for belatacept except older recipient age for PTA. No difference in median kidney, pancreas, or patient survival was observed compared to control. Pancreas rejection occurred in two SPKs. There were two death censored pancreas allograft failures, both PTAs. Kidney allografts failed in two SPK and one PAK. Eight patients died. Six were still receiving belatacept at time of death with functioning allografts. Belatacept use after PTx is safe and can provide some renal recovery. Belatacept was initiated with eGFR approaching 20 mL/min/1.73m2. Earlier introduction may result in better outcomes

PedBE age and age acceleration in umbilical vein endothelial cells: An examination of infant birth outcomes

The current study examines the application of the Pediatric-Buccal-Epigenetic (PedBE) clock, designed for buccal epithelial cells, to endothelia. We evaluate the association of PedBE epigenetic age and age acceleration estimated from human umbilical vein endothelial cells (HUVECs) with length of gestation and birthweight in a racially and ethnically diverse sample (analytic sample n = 333). PedBE age was positively associated with gestational age at birth (r = 0.22, p < .001) and infant birth weight (r = 0.20, p < .001). Multivariate models revealed infants with higher birth weight (adjusted for gestational age) had greater PedBE epigenetic age acceleration (b = 0.0002, se = 0.0007, p = 0.002), though this effect was small; findings were unchanged excluding preterm infants born before 37 weeks' gestation. In conclusion, the PedBE clock may have application to endothelial cells and provide utility as an anchoring sampling point at birth to examine epigenetic aging in infancy

E2 Tyrosine 102 Regulates MmuPV1 Pathogenesis In Vivo

The papillomavirus (PV) life cycle is strictly controlled and can be divided into the following three distinct stages: initial infection, maintenance, and amplification. The papillomavirus E2 gene encodes a multifunctional protein responsible for regulating transcription and replication by recruiting viral and host factors to the viral DNA genome. Our lab has previously reported that tyrosine 102 may impact bovine (BPV) and human (HPV) viral replication in cell culture systems. This tyrosine is conserved in the E2 protein of the murine papillomavirus MmuPV1. To investigate how this amino acid impacts the MmuPV1 lifecycle in vivo, we generated potential phosphorylation mimetic (Y102E) and phosphorylation deficient (Y102F) mutants in the E2 open reading frame. The Y102F mutant protein supported both transcriptional activation and transient replication, while Y102E was defective. However, Y102E was capable of associating with E1 and the Brd4 C-terminal motif. When these E2-mutated MmuPV1 genomes were introduced into the skin of immunocompromised mice, only Y102F was capable of inducing papilloma development and production of infectious progeny virus. These findings demonstrate that while highly conserved, tyrosine at this position is not required by the virus. These data suggest that the chemical nature of the amino acid at this position can influence E2 activity and viral replication

Decoding Secondary Motor Cortex Neuronal Activity During Cocaine Self-Administration: Insights From Longitudinal In Vivo Calcium Imaging

Background: We recently reported that cocaine relapse risk is linked to hyperexcitability in the secondary motor cortex (M2) after prolonged withdrawal following intravenous self-administration (IVSA). However, the neuronal mechanisms underlying drug-taking behaviors and the response of M2 neurons to contingent drug delivery remain poorly understood. Methods: Mice received cocaine as reinforcement (reinforcers [RNFs]) following active lever presses (ALPs) but not inactive lever presses (ILPs). Using miniScopes for in vivo calcium imaging during cocaine IVSA, we tracked M2 neuronal activity with single-cell resolution. Then we analyzed Ca2+ transients in the M2 at the early versus late stages during the 1-hour daily sessions on day 1 and day 5. Results: M2 neurons adapted to both operant behaviors and drug exposure history. Specifically, saline mice showed a reduction in both saline-taking behaviors and Ca2+ transient frequency with the 1-hour session. In contrast, cocaine mice maintained high ALP and RNF counts, with increased Ca2+ transient frequency and amplitude on day 1, persisting through day 5. Compared with saline control mice, cocaine mice exhibited a lower percentage of positively responsive neurons and a higher percentage of negatively responsive neurons before ALPs and after RNFs, a difference not seen before ILPs. Furthermore, as drug-taking behaviors progressed during the daily session, cocaine mice showed greater neuronal engagement with a larger population, particularly linked to ALPs and RNFs, with reduced overlap in neurons associated with ILPs. Conclusions: The M2 undergoes dynamic neuronal adaptations during drug-taking behaviors, supporting its role as a potential substrate mediating the persistence of drug-seeking behaviors in cocaine relapse

Transforming health in Nepal: a historical and contemporary review on disease burden, health system challenges, and innovations

Introduction: Nepal witnessed a tumultuous journey over past two centuries, marked by significant political, social, and cultural shifts. From fighting British colonial encroachments in 1800s, the dynastic Rana regime (1846-1951), and democracy movements in the late 1950s, 1990s and 2000s, Nepal became a federal republic in 2008. The main objective of this review is to lay out an interpretative summary on Nepal's epidemiological transition (includes general trends and disease specific topics) followed by discussion on health system development over key periods: historical period (-1950s), modern period (1950-1990), post-democracy (1991-2016), and post-federalization (2016-). Methods: We conducted a scoping review of available literature using the Arksey and O'Malley framework to synthesize the key insights. Searches were performed in PubMed (via NLM), Embase and Google Scholar using a combination of search terms related to Nepal's health system, epidemiological transition, disease burden and emerging health issues. A total of 1204 records were identified, of which 123 documents - including peer-reviewed articles, government reports and grey literature - met the inclusion criteria. Results: Major advances in maternal and child health, nutritional health and reduction of infectious diseases have been observed in recent decades. The maternal mortality ratio (MMR) declined by 55% (1996-2016), and neonatal mortality halved (40 to 20 per 1000 live births) due to improved antenatal care, skilled birth attendance and family planning. Stunting rates fell from 66% (1996) to 25% (2022), yet rising non-communicable diseases (NCDs) pose new challenges. Communicable diseases, once dominant, have declined owing to expanded immunization and tuberculosis control. However, NCDs now account for over two thirds of deaths, driven by urbanization, ageing and lifestyle shifts. Health system gaps persist, with workforce shortages, rural-urban disparities and out-of-pocket health costs limiting access. Addressing rising health inequities, digital health innovations and service expansion is critical to achieving universal health coverage and sustaining Nepal's health gains. Conclusions: Nepal's health care landscape has continuously evolved over the past centuries, coinciding with key demographic and political changes. Advances through innovation are necessary for the country's overstretched health system to reduce the cost of health services whilst increasing quality and access

Impact of Infectious Diseases Consultation for Patients with Enterococcal Bacteremia: a Retrospective Cohort Study

Background: Gram-positive bacteremia is a challenging cause of morbidity and mortality. Past publications have shown improved patient outcomes and increased adherence to recommended standards of care with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia1. Enterococcus species are another common cause of gram-positive bacteremia with significant morbidity and mortality. This study aims to assess the impact of IDC on the care of patients with Enterococcal bacteremia. Methods: A retrospective chart review was performed on 227 inpatients with at least one blood culture growing an Enterococcus species between June 2022 and November 2023. Patient characteristics collected included age, Charlson Comorbidity index, presence of endocarditis, source of bacteremia, and consultation of the inpatient ID service. Outcomes assessed included in-hospital and 30-day mortality, 30-day re-admission rate, acquisition of repeat blood cultures to document clearance of bacteremia, transthoracic (TTE) and/or transesophageal echocardiography (TEE), and anti-Enterococcal antibiotic duration. Categorical variables were compared with Chi-square or Fisher’s exact tests. Continuous variables were compared with independent t-tests or Mann-Whitney U nonparametric tests. Results: Of 227 patients, 195 (85.8%) received IDC while 32 (14.2%) did not. Patients in both groups had similar Charlson comorbidity indices. 23 (11.7%) patients had Enterococcal endocarditis, all of whom received IDC (Table 1). Patients with IDC had a significantly higher rate of acquisition of clearance blood cultures (98.96% vs. 83.87%, p 76.80% vs. 56.25%, p = .014), and TEE (20.21% vs 0.0%, P = .005) (Table 2). There were no significant differences in in-hospital mortality, 30-day mortality, 30-day re-admission rate, or duration of anti-Enterococcal antibiotics. Conclusions: These results support the conclusion that patients with Enterococcal bacteremia who received IDC were more likely to be managed according to currently recommended standards of care. In this cohort, IDC did not have a statistically significant association with differences in mortality, re-admission rate, or antibiotic duration. Patients with Enterococcal bacteremia are likely to benefit from IDC, especially as they frequently have significant life-limiting co-morbidities complicating their care

Improving youth access to behavioral health services through integrated care and task shifting: protocol for a cluster-randomized stepped wedge clinical trial

Background: One promising solution for improving access to mental health services is integrated behavioral health models, in which behavioral health providers address mental health problems within the primary care infrastructure. Additionally, task-shifting, where non-specialists deliver certain services in the place of specialists, may be well-suited to address mental health provider shortages. The current study outlines the protocol for a hybrid type III implementation-effectiveness, cluster-randomized stepped wedge trial to evaluate the implementation of an adapted pediatric integrated behavioral health model (Peds IBH) that includes task-shifting services, explore the facilitators and barriers to the implementation of Peds IBH, and examine connection to behavioral health care pre- and post-implementation. Methods: The trial will include 25 pediatric primary care clinics across 13 counties in a large healthcare system. Clinics will be randomized to one of three cohorts, stepped in at 6-month intervals, with a 12-month implementation period. The Peds IBH program will: 1) incorporate task-shifting to treat mild to moderate anxiety, depression, and conduct problems with flexible, transdiagnostic cognitive-behavior therapy to be delivered by bachelor's level interventionists, 2) leverage existing child psychiatry provider consultation programs, and 3) increase sustainability through a different billing model. Quantitative data collection will include surveys (primary care team members, behavioral health providers, and youth and caregivers) and tracking of implementation strategies. Qualitative interviews will be conducted with primary care providers and staff. Discussion: This trial will evaluate the implementation of the Peds IBH program. While the focus is implementation outcomes, we will assess effectiveness to inform future dissemination efforts