Adherence to Guidelines and Federal Psychotropic Medication Labels for the Treatment of Medicaid-Insured Children With ADHD.

OBJECTIVE: This study examined adherence to clinical practice guidelines (CPGs) and U.S. Food and Drug Administration (FDA) medication labels when prescribing psychotropic medications to Medicaid-insured children with attention-deficit hyperactivity disorder (ADHD). METHODS: A retrospective analysis was conducted with 2016-2018 Medicaid claims data across 46 states for children with an ADHD diagnosis and at least one psychotropic medication prescription (N=1,236,068 children). Medications recommended for pediatric use were identified with CPGs from the American Academy of Child and Adolescent Psychiatry and the Florida Medicaid Drug Therapy Management Program for Behavioral Health. RESULTS: Across 46 states, 86.7% of children received guideline-recommended and FDA-approved medications for the treatment of ADHD and comorbid mental disorders. Antidepressants, antihistamines, and second-generation antipsychotics that were not included in CPGs were prescribed for 23.4% of children. CONCLUSIONS: High adherence to CPGs and FDA medication labels for medications prescribed for ADHD was observed, suggesting the effectiveness of guidelines in driving evidence-based care.

Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemm's Canal Anatomy and Segmental Pilocarpine Response.

Purpose: To use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration. Methods: Anterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes. Results: Circumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045). Conclusion: High-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

Multifocal Renal Infarction and Diabetic Ketoacidosis: Diagnostic Challenges and Anticoagulation Management in a Complex Case.

BACKGROUND Incidental findings of renal infarct secondary to thrombosis in acutely ill patients present a unique challenge in diagnosis. We present a case of idiopathic renal infarct to highlight its workup and management and encourage further investigation of renal infarctions. CASE REPORT A 68-year-old woman with a past medical history of diet-controlled diabetes, hypertension, and hyperlipidemia presented to the Emergency Department (ED) for abdominal pain. She was found to be in diabetic ketoacidosis with pyelonephritis, so she was admitted to the Intensive Care Unit (ICU) for insulin and dextrose drip. Due to her abdominal pain, she underwent computed tomography (CT) of her abdomen and pelvis with contrast. This revealed multifocal infarcts of her right kidney with noncalcified thrombus at the proximal right renal artery. Subsequent CT angiography confirmed a right renal artery thrombus. She was started on subcutaneous enoxaparin and downgraded to basic level of care. Her history was negative for prior thrombosis, hypercoagulable state, and abdominal trauma. Echocardiogram and limited hypercoagulable workup were largely unremarkable. A multidisciplinary team evaluated the patient and recommended no surgical intervention. Following downgrade from the ICU, the patient was transitioned from enoxaparin to apixaban. She was discharged with plans for anticoagulation for 6 months, aspirin daily, and repeat CT angiogram abdomen/pelvis in 1 month. CONCLUSIONS This case illustrates the difficulties in elucidating the cause of incidental renal thrombosis in an acutely ill patient. Diagnostic workup is limited in the inpatient setting, but therapeutic anticoagulation remains the standard of treatment regardless of etiology.

Novel Self-Calibrated Threshold-Free Probabilistic Fibrosis Signature Technique for 3D Late Gadolinium Enhancement MRI.

Myocardial fibrosis, marked by excessive collagen buildup in the heart, is a crucial severity marker of heart muscle injury in several heart diseases, such as myocardial infarction, cardiomyopathies, and atrial fibrillation (AF). It is also vital for evaluating the efficacy of induced scarring (dense fibrosis) post-interventions, such as catheter ablation for AF. Cardiac MRI emerged as the gold standard for evaluating myocardial fibrosis and scarring for diagnosis and intervention planning. However, existing 3D cardiac MRI (CMR) fibrosis analysis methods are unreliable as they rely on variable thresholding and suffer from a lack of standardization and high sensitivity to typical MRI uncertainties. Importantly, these methods quantify severity based on fibrosis volume alone while ignoring the unique MRI characteristics of fibrosis distribution, which could better inform on disease severity. To address these limitations, we propose a novel thresholdfree and self-calibrating probabilistic method named "Fibrosis Signatures" for a comprehensive and reliable fibrosis analysis of 3D MRI cardiac images. Through a novel efficient (linear complexity) probabilistic encoding of 'multibillion' MRI intensity disparities into standardized probability density function, our method derives the patient's unique fibrosis signature profile and index (FSI). Our approach goes beyond mere measuring of fibrosis volume; it encodes both the extent and the unique MRI characteristics of fibrosis distribution beyond mere entropy for a more detailed evaluation of fibrosis burden/severity. Our self-calibrating design effectively adjusts for MRI uncertainties like noise, low spatial resolution, and segmentation errors to ensure robust and reproducible fibrosis evaluation pre- and post-intervention. Validated in numerical phantom and 143 in vivo MRI scans of AF patients and compared to five baseline methods, our method showed strong correlations with traditional volume measures of pre-intervention fibrosis and post-intervention scar and was up to 9- times more reliable and reproducible, highlighting its potential to enhance cardiac MRI's utility.

Effectiveness of Track Cauterization in Reduction of Adverse Events for Lung Microwave Ablation.

PURPOSE: To evaluate the effectiveness of track cautery for lung microwave ablation (MWA) to reduce post-procedural adverse events (AE). METHODS AND MATERIALS: Patients who underwent percutaneous lung MWA between 2012 to 2021 were divided into patients in whom track cautery was conducted during antenna removal and patients in whom the antenna was simply removed. Patient demographics, treatment history, tumor characteristics, and ablation details were collected. Post-procedural AEs including immediate, enlarging, and delayed pneumothorax (PTX), pleural effusion, and reinterventions were recorded. Univariate and multivariate logistic regression models were used to identify factors associated with AEs. RESULTS: This study included 365 lung MWA sessions for 190 patients. Of the 165 cautery cohort, 78/165 (47%) had immediate PTX, 16/165 (10%) had enlarging PTX, 2/165 (1%) had delayed PTX, and 15/165 (9%) needed interventions. Of the 200 non-cautery cohort, 85/200 (43%) had immediate PTX, 45/200 (23%) had enlarging PTX, 16/200 (8%) had delayed PTX, and 37/200 (19%) needed interventions. The cautery cohort had significantly reduced rates of enlarging PTX (OR 0.67 [95%CI 0.34-1.33], P=0.002), delayed PTX (OR 0.15 [95%CI 0.03-0.89], P=0.037), and pleural effusion (OR 0.38 [95%CI 0.15-0.99], p=0.049). The presence of emphysema, large tumor size, and left lower lobe location were shown to be significant predictors of AEs and the need for interventions (p<0.05). CONCLUSION: Track cauterization is associated with reduction of post-MWA enlarging PTX, delayed PTX, and pleural effusion. Presence of emphysema, lack of track cautery, large tumor size, and tumors in the left lower lobe were shown to be predictors of postprocedural AEs.

Diverse Engraftment Capability of Neuroblastoma Cell Lines in Zebrafish Larvae.

Xenotransplantation of neuroblastoma cells into larval zebrafish allows the characterization of their in vivo tumorigenic abilities and high-throughput treatment screening. This established preclinical model traditionally relies on microinjection into the yolk or perivitelline space, leaving the engraftment ability of cells at the hindbrain ventricle (HBV) and pericardial space (PCS), sites valuable for evaluating metastasis, angiogenesis, and the brain microenvironment, unknown. To address this gap in knowledge, Casper zebrafish at 48 h postfertilization were microinjected with approximately 200 Kelly, Be(2)-C, SK-N-AS, or SY5Y cells into either the HBV or PCS. Fish were imaged at 1, 3, and 6 days postinjection and tumor growth was monitored at each timepoint. We hypothesized that engraftment ability and location preference would be cell line dependent. Kelly and SK-N-AS cells were able to engraft at both the HBV and PCS, with a near doubling in size of tumor volume during the 6 days observation period, with cells appearing to grow better in the HBV. Be(2)-C tumors remained static while SY5Y tumors decreased in size, with almost complete loss of volume at both sites. Therefore, the capability of neuroblastoma cell engraftment in zebrafish larvae is cell line dependent with a location preference.

Genitourinary Ultrasound.

Renal and genitourinary (GU) complaints are common reasons for presentation to the emergency department (ED). This article reviews the approach to renal, bladder, and testicular point-of-care ultrasound (POCUS) with specific discussions of commonly encountered ED pathology. It presents algorithms highlighting the clinical integration of renal and GU POCUS into the evaluation and management of these patients.

When Fulfilling a Professional Obligation Causes Moral Distress: A New Evaluative Approach.

PURPOSE: The term 'moral distress' was coined by Andrew Jameton to name the anguish that clinicians feel when they cannot pursue what they judge to be right because of institutional constraints. We argue that moral distress in critical care should also be addressed as a function of the constraints of ethics and propose an evaluative approach to the experience considering its implications for professional identity. METHOD: We build on a selective review of the literature and analyze a paradigmatic example of moral distress, namely, clinicians who feel compelled to perform procedures on patients that seem futile. Such cases are commonly cited by clinicians as among the most morally distressing. RESULTS: Our analysis shows that (1) physicians' experiences of moral distress can stem not only from toxic workplace cultures and institutional constraints on their time and resources for patient care but also from the limits of ethical reasoning and (2) an emotion-based evaluative approach to analyzing moral distress is needed to address its hazards for professional identity. CONCLUSION: We propose a new evaluative approach to moral distress with implications for professional identity and the need for institutional education and support.

Innovative Strategies in 3D Bioprinting for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is a catastrophic condition that disrupts neurons within the spinal cord, leading to severe motor and sensory deficits. While current treatments can alleviate pain, they do not promote neural regeneration or functional recovery. Three-dimensional (3D) bioprinting offers promising solutions for SCI repair by enabling the creation of complex neural tissue constructs. This review provides a comprehensive overview of 3D bioprinting techniques, bioinks, and stem cell applications in SCI repair. Additionally, it highlights recent advancements in 3D bioprinted scaffolds, including the integration of conductive materials, the incorporation of bioactive molecules like neurotrophic factors, drugs, and exosomes, and the design of innovative structures such as multi-channel and axial scaffolds. These innovative strategies in 3D bioprinting can offer a comprehensive approach to optimizing the spinal cord microenvironment, advancing SCI repair. This review highlights a comprehensive understanding of the current state of 3D bioprinting in SCI repair, offering insights into future directions in the field of regenerative medicine.

One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy.

Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Moreover, our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

MicroRNA-375 modulates neutrophil chemotaxis via targeting Cathepsin B in zebrafish.

Neutrophils are crucial for defense against numerous infections, and their migration and activations are tightly regulated to prevent collateral tissue damage. We previously performed a neutrophil-specific miRNA overexpression screening and identified several microRNAs, including miR-375, as potent modulators for neutrophil activity. Overexpression of miR-375 decreases neutrophil motility and migration in zebrafish and human neutrophil-like cells. We screened the genes downregulated by miR-375 in zebrafish neutrophils and identified that Cathepsin B (Ctsba) is required for neutrophil motility and chemotaxis upon tail wounding and bacterial infection. Pharmacological inhibition or neutrophil-specific knockout of ctsba significantly decreased the neutrophil chemotaxis in zebrafish and survival upon systemic bacterial infection. Notably, Ctsba knockdown in human neutrophil-like cells also resulted in reduced chemotaxis. Inhibiting integrin receptor function using RGDS rescued the neutrophil migration defects and susceptibility to systemic infection in zebrafish with either miR-375 overexpression or ctsba knockout. Our results demonstrate that miR-375 and its target Ctsba modulate neutrophil activity during tissue injury and bacterial infection in vivo, providing novel insights into neutrophil biology and the overall inflammation process.

Medical Student Perspectives on Professionalism in a Third-Year Surgery Clerkship - A Mixed Methods Study.

OBJECTIVE: The norms governing surgical training warrant a deeper understanding of students' experiences and interpretations of professionalism issues in their learning environment. However, there is scant empirical evidence to describe this process. To fill this gap, we analyzed students' perceptions related to professionalism, moral distress, and communication in the surgical clerkship, particularly regarding their clinical supervisors, whom we refer to as mentors. DESIGN: We retrospectively evaluated written case vignettes and survey responses from medical students on their surgical clerkships regarding their experiences of cases which raised professionalism concerns. Vignettes and surveys were part of standard curricular exercises and analyzed using both qualitative and quantitative methods. SETTING: Our study was conducted at a private academic medical college in the northeast with an affiliated institute of bioethics. PARTICIPANTS: Two-hundred forty-one third year medical students on their surgical clerkships participated through required curricular submissions of case vignettes and surveys. RESULTS: Vignettes and surveys from all 241 students were collected and analyzed. Of these, 106 (43.9%) were identified by the students as relating to professionalism, whereas the research team identified 148 (61.4%) cases as such. Major subtypes of professionalism concerns were categorized as "not showing proper respect" (38.5%), bias (30.4%) and "failure to meet medical standards of care" (29.1%). In professionalism cases, only 27.7% of students would emulate their mentor, 19.7% shared concerns with the mentor, and 58.8% experienced moral distress, all significantly worse than in nonprofessionalism cases (p < 0.001). CONCLUSIONS: With an abundance of professionalism concerns noted, students experienced high rates of moral distress and were unlikely to share concerns with clinical mentors who they generally did not wish to emulate. Attention should be paid to providing a formal curricular venue in which students can discuss their concerns, as untoward experiences in the learning environment risk harming their learning and professional identity development.

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

In vivo quantification of anterior and posterior chamber volumes in mice: implications for aqueous humor dynamics.

Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometery. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior, but not the posterior, chamber. Previous fluorophotometric studies of aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans. Our goal was to measure anterior and posterior chamber volumes in mice to facilitate better estimates of aqueous inflow rates. Methods: We used standard near-infrared optical coherence tomography (OCT) and robotic visible-light OCT (vis-OCT) to visualize, reconstruct and quantify the volumes of the anterior and posterior chambers of the mouse eye in vivo. We used histology and micro-CT scans to validate relevant landmarks from ex vivo tissues to facilitate in vivo measurement. Results: Posterior chamber volume is 1.1 times the anterior chamber volume in BALB/cAnNCrl mice, i.e. the anterior chamber constitutes about 47% of the total aqueous humor volume, which is very dissimilar to the situation in humans. Anterior chamber volumes in 2-month-old BALB/cAnNCrl and 7-month-old C57BL6/J mice were 1.55 ± 0.36 µL (n=10) and 2.41 ± 0.29 µL (n=8), respectively. This implies that previous studies likely over-estimated aqueous inflow rate by approximately two-fold. Conclusions: It is necessary to reassess previously reported estimates of aqueous inflow rates, and thus aqueous humor dynamics in the mouse. For example, we now estimate that only 0-15% of aqueous humor drains via the pressure-independent (unconventional) route, similar to that seen in humans and monkeys.

Gastroesophageal Disease and Environmental Exposure: A Systematic Review.

Environmental exposure-associated disease is an active area of study, especially in the context of increasing global air pollution and use of inhalants. Our group is dedicated to the study of exposure-related inflammation and downstream health effects. While many studies have focused on the impact of inhalants on respiratory sequelae, there is growing evidence of the involvement of other systems including autoimmune, endocrine, and gastrointestinal. This systematic review aims to provide a recent update that will underscore the associations between inhalation exposures and upper gastrointestinal disease in the contexts of our evolving environmental exposures. Keywords focused on inhalational exposures and gastrointestinal disease. Primary search identified n = 764 studies, of which n = 64 met eligibility criteria. In particular, there was support for existing evidence that PM increases the risk of upper gastrointestinal diseases. Smoking was also confirmed to be major risk factor. Interestingly, studies in this review have also identified waterpipe use as a significant risk factor for gastroesophageal reflux and gastric cancer. Our systematic review identified inhalational exposures as risk factors for aerodigestive disease, further supporting the association between environmental exposure and digestive disease. However, due to limitations on our review's scope, further studies must be done to better understand this interaction.