Clinical Scenarios Research Articles

Protocol for Conducting a Systematic Review on Diagnostic Accuracy in Clinical Research

In the landscape of modern medicine, the ability to accurately diagnose various clinical conditions is paramount. As new diagnostic tools continue to emerge, their accuracy must be rigorously assessed before clinical implementation. This paper introduces a systematic review protocol tailored for diagnostic accuracy studies, drawing inspiration from a review on dysphagia screening in post-stroke patients. The protocol, designed with precision and transparency at its core, facilitates a thorough synthesis of evidence, employing tools such as the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and the Standards for Reporting of Diagnostic Accuracy Studies (STARD) checklist for robust evaluation. The protocol emphasizes registration with the PROSPERO database and adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The systematic search approach encompasses a comprehensive exploration of databases and precise keyword combinations. Distinctive inclusion and exclusion criteria, coupled with a dual-reviewer methodology, ensure the selection of high-quality studies. This framework has the potential to serve as a benchmark for systematic reviews in diagnostic accuracy, highlighting the importance of standardization, transparency, and adaptability in clinical research. This approach paves the way for a research methodology that delves deeper into diagnostic tools across various clinical scenarios, promoting evidence-based advancements in patient care.

FOCUS ON MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY

Melanotic neuroectodermal tumor of infancy (MNTI) is a very rare benign neoplasm of probable neurocristic origin. It primarily affects children in the first year of life, with the median age at diagnosis of 4.5 months (range 0-804 months). It usually presents as a fast-growing, painless tumor developing within maxilla, skull bones or mandible but other locations are also possible, especially in older children. The cornerstone of treatment of MNTI is surgery, however local relapses after incomplete tumor excision are common, particularly in patients younger than 2 months of age. Rare cases of multiple recurrent, inoperable or metastatic MNTI pose therapeutic challenges. In such clinical scenarios, various regimens of neoadjuvant chemotherapy based on schemes for neuroblastoma or Ewing sarcoma have been used with partial regressions in some patients, enabling less mutilating delayed surgery. The use of radiotherapy is limited due to very young age of patients with MNTI. No targeted therapies have been found useful so far. Long-term prognosis of localized MNTI is favorable. However, extensive or recurrent lesions can result in functional or esthetic sequelae after surgical removal. Rare cases of malignant/metastatic tumors and MNTI diagnosed in older children have unfavorable outcomes. Further collaborative studies to establish standards of management in patients with MNTI are necessary to improve outcomes and diminish sequalae of surgery. This article presents a literature review on this very rare tumor entity, re-evaluated in the light of the experience gained in the national working groups joined together within the European Cooperative Study Group in Pediatric Rare Tumors (EXPeRT).

Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

Training framework for high-stakes OSCE: Experience from volunteer standardized patients' bank.

Training of standardized patients (SPs) for national high-stakes OSCE helps to ensure a reliable assessment of student performance in various clinical scenarios. However, workflow protocols to train SPs vary. Medical schools adopt specific measures to ensure standardization. We present a development workflow of the SPs' training framework for high-stakes OSCE using a volunteer SPs' bank. Our approach was guided by the social learning theory. Three educators and 17/20 (85%) members of our volunteer SPs' bank worked in a collaborative partnership on the construction of pedagogical content of the training framework comprising three 2-hour sessions. Since SPs have to demonstrate acquired behaviors, intended learning outcomes used the words "apply", "perform" and "participate." A principal part of the evaluation was the achievement of intended learning outcomes by the SPs during 3 formative OSCEs. Seventeen SPs, 356 fourth year medical students and 60 examiners participated. Quantitative and qualitative data were collected by post-session questionnaires and analyzed using descriptive statistics and thematic analysis. Twelve examiners evaluated a mean of 29.7+/-0.14 SD patient-student encounters. In total, 15/16 SPs (93.8%) considered the contact with students as easy and 4 SPs (31%) reported the experience as stressful. Two themes emerged from the free-text comments: "Gaining experience as SP" and "Concerns for evaluated students." The proposed SPs' training framework for high-stakes OSCE may be useful for other medical disciplines and health professions initiating SP-based assessment programs. The strategy of development and evaluation are outlined to guide a successful application of the curriculum standards.

Digital "flipbooks" for enhanced visual assessment of simple and complex brain tumors.

Typical longitudinal radiographic assessment of brain tumors relies on side-by-side qualitative visualization of serial magnetic resonance images (MRIs) aided by quantitative measurements of tumor size. However, when assessing slowly-growing tumors and/or complex tumors, side-by-side visualization and quantification may be difficult or unreliable. Whole-brain, patient-specific "digital flipbooks" of longitudinal scans are a potential method to augment radiographic side-by-side reads in clinical settings by enhancing the visual perception of changes in tumor size, mass effect, and infiltration across multiple slices over time. In this approach, co-registered, consecutive MRI scans are displayed in a slide deck, where one slide displays multiple brain slices of a single timepoint in an array (e.g. 3x5 "mosaic" view of slices). The flipbooks are viewed similar to an animated flipbook of cartoons/photos so that subtle radiographic changes are visualized via perceived motion when scrolling through the slides. Importantly, flipbooks can be created easily with free, open-source software. This article describes the step-by-step methodology for creating flipbooks and discusses clinical scenarios for which flipbooks are particularly useful. Example flipbooks are provided in the Online Supplemental Material.

Does in vitro hemolysis affect measurements of plasma apixaban concentration by UPLC-MS and anti-Xa assay?

Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements. Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability. UPLC-MS measurements showed a mean concentration change of -1.66% (±3.2%, p = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, p = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group. Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.

Automatic detection of facial expressions during the Cyberball paradigm in Borderline Personality Disorder: a pilot study

Borderline Personality Disorder (BPD) symptoms include inappropriate control of anger and severe emotional dysregulation after rejection in daily life. Nevertheless, when using the Cyberball paradigm, a tossing game to simulate social exclusion, the seven basic emotions (happiness, sadness, anger, surprise, fear, disgust, and contempt) have not been exhaustively tracked out. It was hypothesized that these patients would show anger, contempt, and disgust during the condition of exclusion versus the condition of inclusion. When facial emotions are automatically detected by Artificial Intelligence, “blending”, -or a mixture of at least two emotions- and “masking”, -or showing happiness while expressing negative emotions- may be most easily traced expecting higher percentages during exclusion rather than inclusion. Therefore, face videos of fourteen patients diagnosed with BPD (26 ± 6 years old), recorded while playing the tossing game, were analyzed by the FaceReader software. The comparison of conditions highlighted an interaction for anger: it increased during inclusion and decreased during exclusion. During exclusion, the masking of surprise; i.e., displaying happiness while feeling surprised, was significantly more expressed. Furthermore, disgust and contempt were inversely correlated with greater difficulties in emotion regulation and symptomatology, respectively. Therefore, the automatic detection of emotional expressions during both conditions could be useful in rendering diagnostic guidelines in clinical scenarios.

Correlation between the radial artery resistance index and the systemic vascular resistance index: a cross-sectional study.

Ultrasound measurement of the radial resistance index (RRI) in the anatomical snuffbox has been proposed as a useful method for assessing the systemic vascular resistance index (SVRI). This study aims to establish the correlation between SVRI measured by pulmonary artery catheter (PAC) and RRI. A cross-sectional study included all consecutive patients undergoing postoperative (POP) cardiac surgery with hemodynamic monitoring using PAC. Hemodynamic assessment was performed using PAC, and RRI was measured with ultrasound in the anatomical snuffbox. The Pearson correlation test was used to establish the correlation between RRI and SVRI measured using PAC. Hemodynamic behavior concerning RRI with a cutoff point of 1.1 (described to estimate under SVRI) was examined. Additionally, consistency between two evaluators was assessed for RRI using the intraclass correlation coefficient and Bland-Altman analysis. A total of 35 measurements were obtained. The average cardiac index (CI) was 2.73 ± 0.64L/min/m², and the average SVRI was 1967.47 ± 478.33 dyn·s·m²/cm5. The correlation between RRI and SVRI measured using PAC was 0.37 [95% CI 0.045-0.62]. The average RRI was 0.94 ± 0.11. RRI measurements > 1.1 had a mean SVRI of 2120.79 ± 673.48 dyn·s·m²/cm5, while RRI measurements ≤ 1.1 had a mean SVRI of 1953.1 ± 468.17 dyn·s·m²/cm5 (p = 0.62). The consistency between evaluators showed an intraclass correlation coefficient of 0.88 [95% CI 0.78-0.93], and Bland-Altman analysis illustrated adequate agreement of RRI evaluators. For patients in cardiac surgery POP, the correlation between the SVRI measured using PAC and the RRI measured in the anatomical snuffbox is low. Using the RRI as a SVRI estimator for patients is not recommended in this clinical scenario.

The efficacy and safety of patent ductus arteriosus stent versus surgical aortopulmonary shunt in the management of babies with duct dependent circulation: a meta-analysis and review of literature

This meta-analysis aims to comprehensively assess the efficacy and safety of both patent ductus arteriosus (PDA) stents and surgical aortopulmonary shunt (APS) as the initial palliative measures in babies relying on ductal-dependent circulation. This review is essential to compare the outcome of relatively newer catheter-based PDA stent procedure with a surgical APS. By synthesizing existing literature, this review aims to provide insights to inform clinical practice and enhance patient care in this challenging clinical scenario. The methodology involved an extensive search of PubMed and Embase databases using specific keywords and terminology related to mortality, procedural outcomes, and postprocedural complications following PDA stent and APS in cyanotic congenital heart defects (CHD) patients. Six retrospective observational studies met the criteria, with 757 patients included. The analysis showed comparable mortality rates between PDA stents and APS. However, PDA stents were associated with decreased risks of mechanical circulatory support, postprocedural complications, and shorter hospital stays, mechanical ventilation, and intensive care unit stays compared to APS. Notably, patients with pulmonary atresia scheduled for biventricular surgery were more prevalent among those receiving PDA stents. In conclusion, while the risk of mortality is similar between PDA stents and APS, PDA stents offer advantages such as shorter hospital stays and reduced complications. Patient characteristics also vary, with a higher prevalence of intact ventricular septum among those receiving PDA stents.

Primary resistance to selpercatinib in a patient with advanced medullary thyroid cancer.

Selpercatinib, a selective RET kinase inhibitor, has demonstrated remarkable efficacy in treating patients with advanced medullary (MTC) and differentiated thyroid cancer with RET alterations. Primary resistance to selpercatinib is a very uncommon situation, and its underlying mechanisms are poorly understood. We report the case of a 42-year-old female with advanced MTC harboring a somatic M918T RET mutation who exhibited a primary resistance to selpercatinib. Despite prompt treatment initiation after the diagnosis of progressive disease, the patient continued experiencing rapid spread of disease, characterized by the appearance of new metastatic lesions and increased tumor burden. Genomic analysis revealed no additional mutations associated with on-target or off-target resistance. This case highlights a rare clinical scenario of primary resistance to selpercatinib in advanced MTC. While secondary resistance mechanisms have been well-documented, primary resistance remains poorly understood. Possible explanations include tumor heterogeneity and activation of alternative signaling pathways that stills need to be elucidated. Emerging therapies targeting resistance mechanisms and next-generation RET inhibitors offer promising avenues for further investigation.

Central sleep apnea in chronic heart failure with hypoxemia - treatment efficacy and hemodynamic effects of three different treatment modalities: a case report

BackgroundThe optimal treatment for central sleep apnea (CSA) depends on the underlying pathophysiology and should consider the potential for hemodynamic impairment when using positive airway pressure devices. While the long-term effects on overall cardiovascular outcome have been investigated for different device settings, the immediate hemodynamic consequences are not well understood. This is mainly due to a lack of hemodynamic monitoring during routine polysomnographic assessment. The application of most monitoring devices is either restricted by their invasiveness, e.g. in thermodilution, or cannot be used continuously like in echocardiography. Impedance cardiography (ICG), however, enables physicians to implement a continuous non-invasive monitoring of different hemodynamic parameters which can be useful in various clinical scenarios. In sleep medicine, the hemodynamic effect of initiating positive airway pressure treatment in patients with pre-existing heart failure should be of special concern.Case presentationIn this case report, we compare the efficacy of three different treatment modalities in a patient with CSA related to chronic heart failure considering the resolution of respiratory events on polysomnography (PSG). In addition, we outline the hemodynamic effects of each treatment device using ICG for non-invasive hemodynamic monitoring. Regarding the reduction of respiratory central events, long-term oxygen treatment (LTOT) and adaptive servoventilation (ASV) proved to be more efficient compared with automatic positive airway pressure (APAP). Hemodynamically, substantial differences of the cardiac performance were observed between the treatment devices. This especially applied to ASV which led to a pronounced drop in cardiac output.ConclusionOur case report indicates that treatment of CSA may induce significant changes of hemodynamic parameters which would remain undetected during routine polysomnographic assessment. We conclude that non-invasive hemodynamic monitoring may be considered when positive airway pressure treatment is initiated in patients at risk of hemodynamic impairment.

Assessing the diagnostic capability of ChatGPT through clinical case scenarios in dermatology

Assessing the diagnostic capability of ChatGPT through clinical case scenarios in dermatology

A Novel Method on Wound Identification using Machine Learning and Image Processing

Automated wound detection using advanced computer vision techniques has emerged as a promising avenue within the realm of healthcare. This approach offers a streamlined and accurate means of identifying a variety of acute injuries, including bruises, abrasions, and traumatic wounds. Wound identification and assessment are crucial tasks in medical practice, facilitating appropriate treatment planning and monitoring of patient recovery. Traditional methods of wound assessment often rely on visual inspection by healthcare professionals, which can be subjective and time-consuming. In recent years, advances in machine learning (ML) and image processing have offered promising avenues for automating wound identification and analysis. This paper presents a comprehensive review of existing techniques and proposes a novel approach that leverages ML algorithms and image processing methods for accurate wound identification. We discuss various challenges, such as data variability, and provide insights into future research directions to enhance the efficacy and applicability of automated wound identification systems. In this study, we delve into the application of YOLO v8, a cutting-edge real-time object detection framework, for automated wound detection across diverse clinical scenarios

Development and validation of immediate self-feedback very short answer questions for medical students: practical implementation of generalizability theory to estimate reliability in formative examination designs

BackgroundVery Short Answer Questions (VSAQs) reduce cueing and simulate better real-clinical practice compared with multiple-choice questions (MCQs). While integrating them into formative exams has potential, addressing marking time and ideal occasions and items is crucial. This study gathers validity evidence of novel immediate self-feedback VSAQ (ISF-VSAQ) format and determines the optimal number of items and occasions for reliable assessment.MethodsNinety-four third-year pre-clinical students took two ten-item ISF-VSAQ exams on cardiovascular drugs. Each question comprised two sections: (1) Questions with space for student responses and (2) a list of possible correct answers offering partial-credit scores ranging from 0.00 to 1.00, along with self-marking and self-feedback options to indicate whether they fully, partially, or did not understand the possible answers. Messick’s validity framework guided the collection of validity evidence.ResultsValidity evidence included five sources: (1) Content: The expert reviewed the ISF-VSAQ format, and the question was aligned with a standard examination blueprint. (2) Response process: Before starting, students received an example and guide to the ISF-VSAQ, and the teacher detailed the steps in the initial session to aid self-assessment. Unexpected answers were comprehensively reviewed by experts. (3) Internal structure: The Cronbach alphas are good for both occasions (≥ 0.70). A generalizability study revealed Phi-coefficients of 0.60, 0.71, 0.76, and 0.79 for one to four occasions with ten items, respectively. One occasion requires twenty-five items for acceptable reliability (Phi-coefficient = 0.72). (4) Relations to other variables: Inter-rater reliability between self-marking and teacher is excellent for each item (rs(186) = 0.87–0.98,p = 0.001). (5) Consequences: Path analysis revealed that the self-reflected understanding score in the second attempt directly affected the final MCQ score (β = 0.25,p = 0.033). However, the VSAQ score did not. Regarding perceptions, over 80% of students strongly agreed/agreed that the ISF-VSAQ format enhances problem analysis, presents realistic scenarios, develops knowledge, offers feedback, and supports electronic usability.ConclusionElectronic ISF-VSAQs enhanced understanding elevates learning outcomes, rendering them suitable for formative assessments with clinical scenarios. Increasing the number of occasions effectively enhances reliability. While self-marking is reliable and may reduce grading efforts, instructors should review answers to identify common student errors.

Safety and feasibility concerns of radiotherapy in the presence of subcutaneous implantable cardioverter-defibrillator

Abstract Introduction Radiotherapy (RT) in patients with cardiac implantable electronic devices (CIED) is performed increasingly more frequently. Currently, there is no evidence, whether RT in patients with subcutaneous implantable cardioverter-defibrillator (sICD) is feasible and safe. Purpose To perform the first in-vitro analyses using a model of left lung cancer treated with stereotactic body radiotherapy (SBRT) with the presence of an sICD. Methods Three functional sICDs explanted from patients following the heart transplant underwent RT. In one device (No º3), the lead had to be cut during explantation at ~ 3 cm from the tip. A computed tomography-based SBRT plan was calculated for a left lung tumor (located 3.5 cm from the sICD). Three fractions of 18 Gy with a nominal energy of 6 MV were delivered, and the maximum dose calculated for the sICD was 3.5 Gy. Each sICD and lead were placed on an anthropomorphic phantom in the nominal location. The intervals between fractions were 7 days. The next step was a direct irradiation of the sICD with an open-field RT with 25 fractions of 2 Gy, then 2 of 20 Gy, 1 of 40 Gy, and a final fraction of 100 Gy. Before and after each fraction, the devices were interrogated, and to verify whether RT affects the devices in the possibly least optimistic clinical scenario, high-voltage therapies were turned on for each fraction and off for the intervals between them. Results A major depletion in the battery percentage (from 88% to 16%) between the first and second fraction of RT in device No. 2 was observed, while in two other devices, major reductions in the device battery longevity were observed after the third fraction of RT (from 38% to 14% and from 60% to 15%, respectively). The estimated doses for sICDs in those stages of RT were respectively 1.2 Gy, 3.5 Gy, and 3.5 Gy. Due to a significant drop of the battery longevity in device No 2º, only two remaining sICD underwent the open-field RT. During the direct irradiation, an unannounced shock was delivered during the interrogation directly after the 14th fraction of 2 Gy, in a device with a macroscopically intact lead. An external interference was demonstrated, which was interpreted as an arrhythmia in the ventricular fibrillation zone. The complete device reset occurred in both devices after having received approximately 195 Gy. Conclusions The presented findings strongly indicate an association between RT and the malfunction of the sICD occurring in the anthropomorphic phantom model of left lung tumor, as well as the risk of inappropriate shocks during the open-beam direct radiation on the devices.Battery longevities before and after RT

Fostering Diversity and Inclusion in Medicine: Collaborating with Extended Reality and Medical Simulation in the Metaverse

Metaverse is a term used to describe a hypothetical shared virtual space where people can interact with a computer-generated environment and each other, and there are multiple metaverses currently being developed by various companies and organizations. Cooperation in the metaverse is at the core of the ongoing digital revolution that impacts the way we design and deliver overall education and training. Medical simulation is a powerful way to deliver education and training, based on the use of technology and other techniques to recreate clinical scenarios for the purpose of teaching and training healthcare professionals and students. This article is about how to involve learners in a metaverse within the medical simulation field. The key questions that we address are as follows: What is the metaverse today? What will it look like in a few years? How do we enhance medical simulation based on cooperation in the metaverse? How do we engage learners with diversity and inclusion?

Mobile ECG devices in pediatric cardiology: efficacy and accuracy of smart watch and hand-held device in healthy children

Abstract Background and Aim Pediatric arrhythmias require accurate electrocardiogram (ECG) assessment for diagnosis and management. Mobile ECG devices, such as smart watch based and hand-held devices, offer potential advantages in terms of portability and accessibility. This study aimed to compare the efficancy and diagnostic accuracy of ECG tracings obtained using a smart watch and a hand-held device with standard 12-lead ECG tracings in healthy children. Methods ECG data were acquired from healthy pediatric subjects (n=30) aged 4 to 18 years using the smart watch, hand-held device, and standard 12-lead ECG. Single leads were acquired sequentially. The time required for ECG acquisition was recorded for each device. Subsequently, ECG leads were analyzed for voltage, duration, and morphology of waves and intervals, as well as ST segments. Qualitative assessment of leads included morphology comparison of waves and complexes to standard 12-lead ECG and using a physician based quality rating scale. Assessment was performed by two blinded pediatric electrophysiologists. Results We found significant differences in the time required to acquire ECG tracings between the smart watch, standard 12-lead ECG, and hand-held device, with the smart watch being notably slower (median 15 min, 4 min, 1 min, respectively). ECG leads obtained with the smart watch and hand-held device demonstrated comparability to standard 12-lead ECG tracings in terms of quantitative key parameters, including voltage (mV) and duration (ms) of waves and intervals. Qualitative assessment revealed good correlation of the hand-held device with standard 12-lead ECG, while the smart watch performed less well. Conclusions This study suggests that mobile ECG devices offer a diagnostic accuracy comparable to that of standard 12-lead ECGs in healthy children. While the smart watch may be slower in ECG acquisition, acquisition of all 12 standard ECG leads is feasible in this population. The potential of both included mobile devices for pediatric usage in specific clinical scenarios, such as remote monitoring or emergencies, is promising.Graphical Abstract

Update in Pediatric Neurocritical Care: What a Neurologist Caring for Critically Ill Children Needs to Know.

Currently nearly one-quarter of admissions to pediatric intensive care units (PICUs) worldwide are for neurocritical care diagnoses that are associated with significant morbidity and mortality. Pediatric neurocritical care is a rapidly evolving field with unique challenges due to not only age-related responses to primary neurologic insults and their treatments but also the rarity of pediatric neurocritical care conditions at any given institution. The structure of pediatric neurocritical care services therefore is most commonly a collaborative model where critical care medicine physicians coordinate care and are supported by a multidisciplinary team of pediatric subspecialists, including neurologists. While pediatric neurocritical care lies at the intersection between critical care and the neurosciences, this narrative review focuses on the most common clinical scenarios encountered by pediatric neurologists as consultants in the PICU and synthesizes the recent evidence, best practices, and ongoing research in these cases. We provide an in-depth review of (1) the evaluation and management of abnormal movements (seizures/status epilepticus and status dystonicus); (2) acute weakness and paralysis (focusing on pediatric stroke and select pediatric neuroimmune conditions); (3) neuromonitoring modalities using a pathophysiology-driven approach; (4) neuroprotective strategies for which there is evidence (e.g., pediatric severe traumatic brain injury, post-cardiac arrest care, and ischemic stroke and hemorrhagic stroke); and (5) best practices for neuroprognostication in pediatric traumatic brain injury, cardiac arrest, and disorders of consciousness, with highlights of the 2023 updates on Brain Death/Death by Neurological Criteria. Our review of the current state of pediatric neurocritical care from the viewpoint of what a pediatric neurologist in the PICU needs to know is intended to improve knowledge for providers at the bedside with the goal of better patient care and outcomes.

Novel horizons in anticoagulation: the emerging role of factor XI inhibitors across different settings.

Anticoagulants have long been fundamental in preventing and treating thromboembolic disorders, with a recent shift of focus towards direct oral anticoagulants, thanks to their ease of use, efficacy, and safety. Despite these advancements, bleeding complications remain a major concern with any anticoagulant, highlighting the need for safer drugs. Factor XI (FXI) inhibitors have emerged as promising agents in this regard, offering a novel approach by targeting upstream factors in the coagulation system. Phase 2 trials have shown encouraging outcomes, indicating a reduced bleeding risk compared to traditional anticoagulants, particularly in the context of cardiovascular disease management when combined with antiplatelet therapy. However, the variability in findings and limited efficacy data call for a cautious interpretation pending phase 3 trial insights. These trials are essential for validating the potential of FXI inhibitors to balance bleeding risk reduction and maintain anticoagulant efficacy. This review explores the pharmacology, potential indications, clinical data, and future directions of FXI inhibitors, providing a perspective on their evolving role in anticoagulant therapy. It also provides a detailed analysis of data from published clinical trials on FXI inhibitors in various indications. Preliminary data from ongoing trials is also outlined. As the field moves forward, a cautiously optimistic outlook can be expected, focusing on comprehensive data from phase 3 trials to define the role of FXI inhibitors in various clinical scenarios.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.