Contrast-enhanced computed tomography for ex vivo assessment of human kidneys: A proof-of-concept study.

BACKGROUND: Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information. Developing non-invasive, whole organ methods of assessment is critical to the further development of this research platform. METHODS: We use ex vivo cold infusion scanning (EXCIS) with contrast-enhanced computed tomography (CT) to quantify perfusion in kidneys preserved ex vivo. EXCIS-CT computes three complementary metrics for whole organ assessment: a dynamic assessment of contrast filling, a measure of vascular network anatomical structure, and a static assessment of perfusion heterogeneity. RESULTS: These metrics were applied to a series of six transplant-declined human kidneys, which demonstrated a range of anatomies and perfusion. Lastly, two transplant-declined human kidneys were imaged before and after a 1-h period of ex vivo normothermic perfusion (NMP). We found variable responses to NMP, with one kidney maintaining the vascular network and hemodynamics and the other showing significant changes in vessel size and spatial perfusion profile. CONCLUSIONS: EXCIS-CT provides metrics that can be used to characterize whole organ perfusion and vascular function.

Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys.

Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs. In a recent study of 8 transplant-declined human kidneys on NMP, we discovered microvascular obstructions that impaired microvascular blood flow. However, the nature and physiologic impact of these lesions were unknown. Here, in a study of 39 human kidneys, we have identified that prolonged cold storage of human kidneys induces accumulation of fibrinogen within tubular epithelium. Restoration of normoxic conditions-either ex vivo during NMP or in vivo following transplant-triggered intravascular release of fibrinogen correlating with red blood cell aggregation and microvascular plugging. Combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs leading to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular-targeted nanoparticles. Our study suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential.

A Rare Case of Retinal Vasculitis in a Patient With Autoimmune Lymphoproliferative Syndrome.

This report describes a case of retinal vasculitis in a patient with autoimmune lymphoproliferative syndrome (ALPS). A 13-year-old girl undergoing work-up for immune dysregulation was referred for retinal vasculitis. The patient was asymptomatic on presentation, but her retinal examination was remarkable for areas of outer retinal and choriocapillary loss and focal vascular inflammation. Subsequent bone marrow biopsy with genetic sequencing revealed a diagnosis of ALPS, and she was started on immunosuppression. Most cases of ocular ALPS have anterior involvement, but retinal changes may rarely occur in isolation. Patients with ALPS may benefit from routine eye examination and monitoring. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Bilateral tonic pupils secondary to anti-GD2 antibody therapy for neuroblastoma.

We report the case of a 12-year-old girl with stage 4 neuroblastoma who developed tonic pupils secondary to immunotherapy with dinutuximab, an anti-GD2 antibody, based on the timeline provided by her mother with regard to onset of symptoms. The patient presented with difficulty reading and chronic dilated pupils bilaterally, according to her mother's observations over 6 months prior to presentation. Testing with dilute pilocarpine supported our presumption of tonic pupils.

Getting Athletes Back on the Field: Management of Clavicle Fractures and Return to Play.

This chapter provides an overview of the prevalence of clavicle fractures in athletes. The evaluation and management of clavicle fractures in athletes is summarized, including surgical considerations, rehabilitation protocols, and return to sport guidelines. In this population, high rates of union are observed, but careful timing of return to sport is paramount to optimize performance and prevent reinjury.

Atraumatic Sternoclavicular Joint Instability: Prevalence, Etiology, and Management.

Sternoclavicular joint instability is a rare complaint in the orthopedic clinic, but patients can experience chronic pain and functional impacts. Causes of instability may be posttraumatic, infectious, autoimmune, degenerative, or secondary to generalized laxity. Conservative treatment is the initial approach to management and involves activity modification, physical therapy, oral nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgery is indicated when conservative treatment does not manage symptoms. Figure-of-eight reconstruction techniques provide greatest biomechanical strength but are associated with risk of neurovascular injury. Other reconstruction methods have been shown to mitigate these risks with favorable short-term outcomes.

Optimizing Pediatric Mask Induction Fresh Gas Flow.

INTRODUCTION: The environmental impact of inhaled anesthetics is a subject of increasing research. However, little attention has been paid to optimizing high-concentration volatile anesthetics during the inhalational (mask) inductions that begin most pediatric anesthetics. METHODS: The performance of the GE Datex Ohmeda TEC 7 sevoflurane vaporizer was analyzed at different fresh gas flow (FGF) rates and two clinically relevant ambient temperatures. We found that an FGF rate of 5 liters per minute (LPM) is likely optimal for inhalational inductions, rapidly achieving dialed sevoflurane concentrations at the elbow of an unprimed pediatric breathing circuit while minimizing waste associated with higher FGF rates. We began educating our department regarding these findings, first with QR code labels on anesthetic workstations, then with targeted e-mails to pediatric anesthesia teams. We analyzed peak induction FGF in 100 consecutive mask inductions at our ambulatory surgery center at three different periods - baseline, post-labels, and post-emails - to assess the efficacy of these educational interventions. We also analyzed the time from induction to the start of myringotomy tube placement in a subset of these cases to determine if reducing mask induction FGF was associated with any change in the speed of induction. RESULTS: Our institution's median peak FGF during inhalational inductions decreased from 9.2 LPM at baseline to 8.0 LPM after labels were placed on anesthetic workstations to 4.9 LPM after targeted e-mails. There was no associated decrease in the speed of induction. CONCLUSION: Total fresh gas flow can be limited to 5 LPM during pediatric inhalational inductions, decreasing anesthetic waste and environmental impact without slowing the speed of induction. Educational labels on anesthetic workstations and direct e-mails to clinicians were effectively used in our department to enact change in this practice.

The Effect of Computer Tablets on the Need for Medical Anxiolysis in Children in an Ambulatory Surgical Center.

Background Preoperative anxiety is common in children undergoing surgery. When anxiety is identified or suspected, there are several strategies typically used to manage it. Perhaps the most common is anxiolytic premedication or parental presence at induction. Medications such as midazolam have been associated with adverse effects, such as a slower wakeup, and require timing of administration, while parental presence can be disturbing to the parent and divert the attention of the operating room team. A more recent option is distraction via electronic tablets. The purpose of this study was to retrospectively investigate and quantify any change in the use of midazolam, the most common anxiolytic approach at our institution, and any change in the length of time in the post-anesthesia care unit (PACU) following the introduction of tablet computers to a pediatric ambulatory surgical center. Methods We conducted an IRB-approved retrospective chart review of 13,790 pediatric patients ages one to 18 undergoing outpatient elective surgeries at the University of Florida (UF) Children's Surgical Center over a five-year period. A univariate analysis was conducted using the Fisher's Exact test and interrupted time series analysis to determine differences between midazolam administration and PACU times, with interruption occurring at tablet implementation. A multivariable analysis and sensitivity analyses were performed to confirm the findings of the univariate analysis. Results On univariate analysis, tablet availability was associated with both a decreased preoperative oral midazolam administration (odds ratio (OR) 0.158, 95% confidence interval (CI): 0.140 to 0.179, P-value <0.001) and a decreased PACU length of stay (-17.4 min, 95% CI: -19.6 to -15.3 min, P-value <0.001). The association with decreased preoperative midazolam administration held after multivariable analysis (adjusted OR 0.207, 95% CI: 0.154 to 0.278, P-value <0.001), but PACU length of stay was not statistically significant (-9.1 min, 95% CI: -20.6 to 2.4, P-value = 0.12). These results were confirmed on sensitivity analysis, with tablet availability continuing to be associated with decreased preoperative oral midazolam administration but not with reduced PACU length of stay. Conclusion Our results demonstrate that computer tablets were associated with a significant decrease in the frequency of midazolam administration and consequently may reduce preoperative pediatric anxiety. We did not find an associated change in PACU length of stay following the introduction of tablets. Tablets present a unique distraction alternative to chemical anxiolysis for institutions seeking to reduce medication use in pediatric patients.

Genetically Confirmed Malignant Hyperthermia in a Six-Week-Old Infant: A Case Report.

A six-week-old 3.9-kg infant presented for microlaryngoscopy and diaphragmatic hernia repair. While positioning for laparoscopy after microlaryngoscopy, the infant developed muscle rigidity, worsening hypercarbia, tachycardia, and early hyperthermia. Sevoflurane was discontinued, and the clinical picture indicating malignant hyperthermia (MH) resolved without dantrolene. Subsequent genetic testing revealed that both the patient and his father carried a mutation in the RYR1 gene that is diagnostic for MH. This is the second youngest genetically confirmed case of MH. This case adds to a limited body of evidence regarding MH presentation and diagnosis in neonates and infants.