Comparative retrospective assessment of the effectiveness and risk factors of fluoroquinolones, cephalosporines and selective antibiotic prophylaxis for transrectal prostate biopsy.

INTRODUCTION: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. METHODS: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as: fever >38.0°C, in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µl and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, -duration and comorbidities were also assessed. Chi-Square and Fishers exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. RESULTS: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6%, 13.3%, 25%, p<0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p<0.05). Arterial hypertension showed increased association with fever (OR 6.002 [1.178;30.597] p=0.031) and cUTI (OR 6.006 [1.207;29.891] p=0.029). CONCLUSION: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

Control of endothelial cell function and arteriogenesis by MEG3:EZH2 epigenetic regulation of integrin expression.

Epigenetic processes involving long non-coding RNAs regulate endothelial gene expression. However, the underlying regulatory mechanisms causing endothelial dysfunction remain to be elucidated. Enhancer of zeste homolog 2 (EZH2) is an important rheostat of histone H3K27 trimethylation (H3K27me3) that represses endothelial targets, but EZH2 RNA binding capacity and EZH2:RNA functional interactions have not been explored in post-ischemic angiogenesis. We used formaldehyde/UV-assisted crosslinking ligation and sequencing of hybrids and identified a new role for maternally expressed gene 3 (MEG3). MEG3 formed the predominant RNA:RNA hybrid structures in endothelial cells. Moreover, MEG3:EZH2 assists recruitment onto chromatin. By EZH2-chromatin immunoprecipitation, following MEG3 depletion, we demonstrated that MEG3 controls recruitment of EZH2/H3K27me3 onto integrin subunit alpha4 (ITGA4) promoter. Both MEG3 knockdown or EZH2 inhibition (A-395) promoted ITGA4 expression and improved endothelial cell migration and adhesion to fibronectin in vitro. The A-395 inhibitor re-directed MEG3-assisted chromatin remodeling, offering a direct therapeutic benefit by increasing endothelial function and resilience. This approach subsequently increased the expression of ITGA4 in arterioles following ischemic injury in mice, thus promoting arteriogenesis. Our findings show a context-specific role for MEG3 in guiding EZH2 to repress ITGA4. Novel therapeutic strategies could antagonize MEG3:EZH2 interaction for pre-clinical studies.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review.

Background: Headache management after acute brain injury (ABI) is challenging. While opioids are commonly used, selective cyclooxygenase-2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. Methods: A systematic review was conducted through MEDLINE and Embase for articles published through 09/2023 (PROSPERO CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using Distiller SR®. Descriptive statistics were used for data analysis, while meta-analysis was unfeasible due to study heterogeneity. Results: Of 3190 articles identified, six studies met inclusion criteria: four randomized controlled trials and two retrospective cohort studies, all conducted in neurosurgical patients (total n=738) between 2006-2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, while one showed improvement only at 6 hours postoperative, and one did not find significant differences. Pain scores decreased between 4-15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, while one reported a reduction at 12 hours postoperative only. Opioid consumption decreased between 9-90%. Two studies found a decrease in hospital-length-of-stay by ~1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically non-significant 3% reduction in the intervention group. Conclusions: In adults with ABI, COXIBs may serve as opioid-sparing adjunctive analgesics for headache control, with limited but pointed data to indicate efficacy in the post-neurosurgical setting. However, further safety data remains to be elucidated.

Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Guided inquiry-based learning to enhance student engagement, confidence, and learning.

PURPOSE: This study explores the impact of guided inquiry-based learning (IBL) on student engagement and performance in a dental hygiene program. The research was conducted with 36 dental hygiene students, focusing on enhancing student engagement using a guided IBL methodology that could ultimately lead to improved student performance and confidence. METHODS: Delivered through two interventions, pre-, post-, and delayed post-tests evaluated student performance and confidence, while the ASPECT survey assessed student engagement. The interventions included a lecture (intervention #1) and a group-based IBL worksheet activity (intervention #2). Statistical analyses using analysis of variance (ANOVA) tested the impact of these interventions on student performance and confidence-adjusted scores. RESULTS: Results showed significant improvements in student performance and confidence following both interventions, with notably higher gains after the IBL activity. Analysis of ASPECT survey data revealed positive perceptions of engagement, emphasizing the importance of group dynamics, instructor roles, and the activity's value. Students reported enhanced understanding and engagement through group interactions and individual study. The study also highlighted the critical role of the instructor in facilitating and guiding the IBL activity. CONCLUSION: In conclusion, the study demonstrates that guided IBL strategies can significantly enhance student confidence and performance, suggesting a sustainable impact on learning outcomes. These findings underscore the importance of active, engaged learning methodologies in healthcare education, particularly in enhancing long-term retention and understanding of complex topics. The study advocates for integrating such strategies into academic curricula to foster deeper student engagement and improved educational experiences.

Sulforaphane Inhibits Adhesion and Migration of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro.

Only 20% of patients with muscle-invasive bladder carcinoma respond to cisplatin-based chemotherapy. Since the natural phytochemical sulforaphane (SFN) exhibits antitumor properties, its influence on the adhesive and migratory properties of cisplatin- and gemcitabine-sensitive and cisplatin- and gemcitabine-resistant RT4, RT112, T24, and TCCSUP bladder cancer cells was evaluated. Mechanisms behind the SFN influence were explored by assessing levels of the integrin adhesion receptors ß1 (total and activated) and ß4 and their functional relevance. To evaluate cell differentiation processes, E- and N-cadherin, vimentin and cytokeratin (CK) 8/18 expression were examined. SFN down-regulated bladder cancer cell adhesion with cell line and resistance-specific differences. Different responses to SFN were reflected in integrin expression that depended on the cell line and presence of resistance. Chemotactic movement of RT112, T24, and TCCSUP (RT4 did not migrate) was markedly blocked by SFN in both chemo-sensitive and chemo-resistant cells. Integrin-blocking studies indicated ß1 and ß4 as chemotaxis regulators. N-cadherin was diminished by SFN, particularly in sensitive and resistant T24 and RT112 cells, whereas E-cadherin was increased in RT112 cells (not detectable in RT4 and TCCSup cells). Alterations in vimentin and CK8/18 were also apparent, though not the same in all cell lines. SFN exposure resulted in translocation of E-cadherin (RT112), N-cadherin (RT112, T24), and vimentin (T24). SFN down-regulated adhesion and migration in chemo-sensitive and chemo-resistant bladder cancer cells by acting on integrin ß1 and ß4 expression and inducing the mesenchymal-epithelial translocation of cadherins and vimentin. SFN does, therefore, possess potential to improve bladder cancer therapy.

Pediatric Emergency Medicine Didactics and Simulation (PEMDAS): Pediatric Sedation Complications.

Introduction: Ketamine and propofol are commonly used agents for sedation in the pediatric emergency department (PED). While these medications routinely provide safe sedations, there are side effects providers should be able to recognize and manage. Currently, no pediatric sedation simulations exist in the literature. Methods: We created two sedation simulation cases for learners, including pediatric emergency medicine (PEM) fellows, working in the PED: case 1, a 12-year-old male with a shoulder dislocation requiring reduction under propofol sedation, and case 2, a forearm fracture requiring reduction under ketamine sedation. Learner actions included setting up equipment for sedations, dosing medications correctly, and managing complications. Additionally, in case 2, learners assigned an American Society of Anesthesiologists classification and selected the appropriate candidate for PED sedation from amongst three patients. A debrief followed the cases. Next, a didactic presentation reinforced concepts discussed in the debrief. Participants then completed an evaluation of the simulation. Results: Fifty-eight emergency medicine residents and PEM fellows across four sites at three institutions participated. Participants scored the simulations and the debriefing session on a 5-point Likert scale. Learners rated the scenario as clinically relevant (M = 4.37) and effective at improving their comfort level in caring for critically ill patients (M = 4.36). Learners felt the debrief provided valuable learning (M = 4.40) and was a safe learning environment (M = 4.50). Discussion: These cases can be utilized as resources for learners in any emergency department and can be tailored to any training background of learner providing sedation.

Risk Factors for Admission Hyperthermia and Associated Outcomes in Infants Born Preterm.

Maternal, placental, and neonatal factors were compared between infants born at ≤29 weeks of gestational age with admission hyperthermia (>37.5○C) and euthermia (36.5-37.5○C). Admission hyperthermia was associated with longer duration of face-mask positive-pressure ventilation and infant's temperature ≥37.5○C in the delivery room. Infants born preterm with admission hyperthermia had greater odds of developing necrotizing enterocolitis and neurodevelopmental impairment.

Mistletoe Extracts from Different Host Trees Disparately Inhibit Bladder Cancer Cell Growth and Proliferation.

Extracts of European mistletoe (Viscum album) are popular as a complementary treatment for patients with many different cancer types. However, whether these extracts actually block bladder cancer progression remains unknown. The influence of different mistletoe extracts on bladder cancer cell growth and proliferation was investigated by exposing RT112, UMUC3, and TCCSup cells to mistletoe from hawthorn (Crataegi), lime trees (Tiliae), willow trees (Salicis), or poplar trees (Populi). The tumor cell growth and proliferation, apoptosis induction, and cell cycle progression were then evaluated. Alterations in integrin α and ß subtype expression as well as CD44 standard (CD44s) and CD44 variant (CD44v) expressions were evaluated. Cell cycle-regulating proteins (CDK1 and 2, Cyclin A and B) were also investigated. Blocking and knock-down studies served to correlate protein alterations with cell growth. All extracts significantly down-regulated the growth and proliferation of all bladder cancer cell lines, most strongly in RT112 and UMUC3 cells. Alterations in CD44 expression were not homogeneous but rather depended on the extract and the cell line. Integrin α3 was, likewise, differently modified. Integrin α5 was diminished in RT112 and UMUC3 cells (significantly) and TCCSup (trend) by Populi and Salicis. Populi and Salicis arrested UMUC3 in G0/G1 to a similar extent, whereas apoptosis was induced most efficiently by Salicis. Examination of cell cycle-regulating proteins revealed down-regulation of CDK1 and 2 and Cyclin A by Salicis but down-regulation of CDK2 and Cyclin A by Populi. Blocking and knock-down studies pointed to the influence of integrin α5, CD44, and the Cyclin-CDK axis in regulating bladder cancer growth. Mistletoe extracts do block bladder cancer growth in vitro, with the molecular action differing according to the cell line and the host tree of the mistletoe. Integrating mistletoe into a guideline-based treatment regimen might optimize bladder cancer therapy.

Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study.

OBJECTIVE: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. STUDY DESIGN: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score < -2. RESULTS: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0. CONCLUSION: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0. KEY POINTS: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction..

Gamification of a Low-Fidelity Paper Doll to Teach Primary Survey to Pediatric Residents.

When critically ill pediatric patients arrive in the emergency department (ED), a rapid physical evaluation is performed in order to systematically evaluate and address life-threatening conditions. This is commonly referred to as the primary survey. At our institution, pediatric residents are frequently tasked with this role, but they have limited training for or experience with this task. Quality improvement review of real resuscitation recordings at our institution revealed delays in initiation and incomplete primary surveys. We sought to utilize gamification to standardize and optimize reproducible training for the primary survey task for pediatric residents using a low-fidelity paper doll model simulation to improve primary survey performance in actual resuscitations.

Pediatric Toxidrome Simulation Curriculum: Jimson Weed Toxicity.

Introduction: Jimson weed is a poisonous plant containing tropane alkaloids that can cause anticholinergic toxicity. Recognition of anticholinergic toxidrome is important for prevention and management of potentially life-threatening complications of severe toxicity, including dysrhythmia and seizure. Methods: Designed for pediatric emergency medicine (PEM) fellows, this simulation featured a 15-year-old female presenting to the emergency department (ED) with agitation and hallucinations. The team was required to perform a primary survey of the critically ill patient, recognize anticholinergic toxidrome from jimson weed intoxication, and treat complications of severe anticholinergic toxicity. Learners practiced critical resuscitation skills such as management of generalized tonic-clonic seizure, endotracheal intubation, synchronized cardioversion, and external cooling measures. A debriefing guide and participant evaluation forms were utilized. This simulation was created as both an in-person and a virtual simulation experience to accommodate COVID-19 social distancing guidelines. Results: Seventeen PEM fellows completed this simulation across three institutions (two in person, one virtual). Using 5-point Likert scales (with 5 being the most relevant or effective), participants rated the simulation as relevant to their work (M = 4.8, SD = 0.5) as well as effective in teaching basic resuscitation skills (M = 4.7, SD = 0.5), management of generalized tonic-clonic seizure (M = 4.8, SD = 0.5), and treatment of ventricular tachycardia with appropriate interventions (M = 4.6, SD = 0.5). Discussion: This simulation scenario allows pediatric medicine trainees in the ED to practice recognition and management of anticholinergic toxicity and its severe complications secondary to jimson weed ingestion.

The tyrosine kinase inhibitor Dasatinib reduces cardiac steatosis and fibrosis in obese, type 2 diabetic mice.

BACKGROUND: Cardiac steatosis is an early yet overlooked feature of diabetic cardiomyopathy. There is no available therapy to treat this condition. Tyrosine kinase inhibitors (TKIs) are used as first or second-line therapy in different types of cancer. In cancer patients with diabetes mellitus, TKIs reportedly improved glycemic control, allowing insulin discontinuation. They also reduced liver steatosis in a murine model of non-alcoholic fatty liver disease. The present study aimed to determine the therapeutic effect of the second-generation TKI Dasatinib on lipid accumulation and cardiac function in obese, type 2 diabetic mice. We also assessed if the drug impacts extra-cardiac fat tissue depots. METHODS: Two studies on 21-week-old male obese leptin receptor mutant BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db) mice compared the effect of Dasatinib (5 mg/kg) and vehicle (10% DMSO + 90% PEG-300) given via gavage once every three days for a week or once every week for four weeks. Functional and volumetric indices were studied using echocardiography. Post-mortem analyses included the assessment of fat deposits and fibrosis using histology, and senescence using immunohistochemistry and flow cytometry. The anti-adipogenic action of Dasatinib was investigated on human bone marrow (BM)-derived mesenchymal stem cells (MSCs). Unpaired parametric or non-parametric tests were used to compare two and multiple groups as appropriate. RESULTS: Dasatinib reduced steatosis and fibrosis in the heart of diabetic mice. The drug also reduced BM adiposity but did not affect other fat depots. These structural changes were associated with improved diastolic indexes, specifically the E/A ratio and non-flow time. Moreover, Dasatinib-treated mice had lower levels of p16 in the heart compared with vehicle-treated controls, suggesting an inhibitory impact of the drug on the senescence signalling pathway. In vitro, Dasatinib inhibited human BM-MSC viability and adipogenesis commitment. CONCLUSIONS: Our findings suggest that Dasatinib opposes heart and BM adiposity and cardiac fibrosis. In the heart, this was associated with favourable functional consequences, namely improvement in an index of diastolic function. Repurposing TKI for cardiac benefit could address the unmet need of diabetic cardiac steatosis.

BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.

Long-living individuals (LLIs) escape age-related cardiovascular complications until the very last stage of life. Previous studies have shown that a Longevity-Associated Variant (LAV) of the BPI Fold Containing Family B Member 4 (BPIFB4) gene correlates with an extraordinarily prolonged life span. Moreover, delivery of the LAV-BPIFB4 gene exerted therapeutic action in murine models of atherosclerosis, limb ischemia, diabetic cardiomyopathy, and aging. We hypothesize that downregulation of BPIFB4 expression marks the severity of coronary artery disease (CAD) in human subjects, and supplementation of the LAV-BPIFB4 protects the heart from ischemia. In an elderly cohort with acute myocardial infarction (MI), patients with three-vessel CAD were characterized by lower levels of the natural logarithm (Ln) of peripheral blood BPIFB4 (p = 0.0077). The inverse association between Ln BPIFB4 and three-vessel CAD was confirmed by logistic regression adjusting for confounders (Odds Ratio = 0.81, p = 0.0054). Moreover, in infarcted mice, a single administration of LAV-BPIFB4 rescued cardiac function and vascularization. In vitro studies showed that LAV-BPIFB4 protein supplementation exerted chronotropic and inotropic actions on induced pluripotent stem cell (iPSC)-derived cardiomyocytes. In addition, LAV-BPIFB4 inhibited the pro-fibrotic phenotype in human cardiac fibroblasts. These findings provide a strong rationale and proof of concept evidence for treating CAD with the longevity BPIFB4 gene/protein.

Pediatric Emergency Medicine Didactics and Simulation: JumpSTART Secondary Triage for Mass Casualty Incidents.

Mass casualty incidents (MCI), particularly involving pediatric patients, are high-risk, low-frequency occurrences that require exceptional emergency arrangements and advanced preparation. In the aftermath of an MCI, it is essential for medical personnel to accurately and promptly triage patients according to their acuity and urgency for care. As first responders bring patients from the field to the hospital, medical personnel are responsible for prompt secondary triage of these patients to appropriately delegate hospital resources. The JumpSTART triage algorithm (a variation of the Simple Triage and Rapid Treatment, or START, triage system) was originally designed for prehospital triage by prehospital providers but can also be used for secondary triage in the emergency department setting. This technical report describes a novel simulation-based curriculum for pediatric emergency medicine residents, fellows, and attendings involving the secondary triage of patients in the aftermath of an MCI in the emergency department. This curriculum highlights the importance of the JumpSTART triage algorithm and how to effectively implement it in the MCI setting.

Characteristics and Prescribing Patterns of Clinicians Waivered to Prescribe Buprenorphine for Opioid Use Disorder Before and After Release of New Practice Guidelines.

Importance: In April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine. Objective: To compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines. Design, Setting, and Participants: This survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021. Exposure: DATA waiver approval pathway. Main Outcome and Measures: The outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups. Results: Of 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing. Conclusions and Relevance: In this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access.