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Although neuraxial techniques such as caudal and epidural anesthesia were initially the predominant regional anesthetic technique used to provide postoperative analgesia in children, there has been a transition to the use of peripheral nerve blockade such as the quadratus lumborum block (QLB). We present preliminary experience with QL catheters for continuous postoperative analgesia in a cohort of pediatric patients following colorectal surgery.After institutional review board (IRB) approval, we retrospectively reviewed the records of patients who underwent major colorectal surgery and received QL catheters for postoperative analgesia. The postoperative pain control data consisted of QL catheter characteristics, anesthetic agents, adjuncts, pain scores, and opioid consumption during the postoperative period.The study cohort included eight pediatric patients, ranging in age from 1 to 19 years (median age 11.8 years). The QL catheters were placed in the operating room after the induction of anesthesia. Comorbid conditions in the cohort that were contraindications to neuraxial anesthesia included spinal/vertebral malformations, presence of a ventriculoperitoneal (VP) shunt, anal atresia, tracheo-esophageal fistula (VACTERL) association, and coagulation disturbances. All patients underwent complex colorectal or genito-urologic procedures. Bilateral QL catheters were placed in six patients, and unilateral catheters were placed in two patients. Four patients received 0.5% ropivacaine and four patients received 0.2% ropivacaine of an initial bolus. The local anesthetic used for continuous infusion was 0.2% ropivacaine in five patients, 0.1% ropivacaine in two patients, and 1.5% chloroprocaine in one patient, with a median infusion rate of 0.11 mL/kg/h. QL catheter infusions were supplemented with intravenous opioids delivered by patient-controlled or nurse-controlled analgesia. The median opioid requirements in oral morphine milligram equivalents (MME) were 1.2, 1.0, 1.1, 0.5, and 0.6 MME/kg on postoperative days 1 - 5. Daily median pain scores were ≤ 2 during the 5-day postoperative course. All catheters functioned successfully and were in place for a median of 79.3 h. Other than early inadvertent removal of two catheters, no adverse effects were noted.Although our preliminary data suggest the efficacy of QL catheters in providing prolonged postoperative analgesia for up to 3 - 5 days following colorectal procedures, attention needs to be directed at measures to ensure that the catheter is secured to avoid inadvertent removal.

Pneumonia is the third most common surgical complication after urinary tract infection and wound infections. In addition to increased mortality, patients who develop postoperative pneumonia have a higher risk of prolonged hospital stay, intensive care unit (ICU) admissions, and higher healthcare costs. Obesity and chronic obstructive pulmonary disease (COPD) are both independent risk factors for the development and severity of postoperative pneumonia, although the combined effect of these comorbidities is unknown. Therefore, we evaluated whether the combination of severe obesity and COPD is associated with an increased risk of postoperative pneumonia.We performed a multicenter retrospective cohort study of 365,273 patients aged 18 - 64 years who were either severely obese (body mass index (BMI) ≥ 40 kg/mThe co-occurrence of severe obesity and COPD appeared to have a protective effect on the risk of postoperative pneumonia. In the presence of COPD, patients with severe obesity were 14% less likely to develop pneumonia compared to their normal-weight counterparts (2.9% vs. 4.4%; adjusted relative risk (RR): 0.76; 95% confidence interval (CI): 0.60, 0.95). In addition, in the presence of COPD, severe obesity conferred a lower risk for requiring an extended length of stay (37.6% vs. 47.9%; adjusted RR: 0.83; 95% CI: 0.78, 0.89).Counterintuitively, the co-occurrence of severe obesity with COPD appeared to buffer the negative impact of COPD on postoperative pneumonia, unplanned tracheal reintubation, and prolonged hospital stay after noncardiac surgery. These findings are consistent with the obesity paradox and warrant further investigations.

Background: Positron emission tomography (PET)/computed tomography (CT) imaging can detect changes in arterial inflammation, but has not been used to evaluate chemotherapy-induced venous inflammation or assess risk for venous thromboembolism (VTE) in pediatric oncology. Therefore, the purpose of this study was to evaluate the prognostic value of fluorine-18-fluorodeoxyglucose PET/CT imaging of venous inflammation for predicting VTE occurrence in the 12 months after lymphoma diagnosis in pediatric, adolescent, and young adult patients. Methods: Pediatric, adolescent, and young adult patients with lymphoma diagnoses (n=71) who underwent whole-body PET/CT imaging at initial staging of disease and first therapeutic follow-up were retrospectively evaluated for serial changes in lower extremity venous uptake of fluorine-18-fluorodeoxyglucose. PET/CT images were used to segment and quantify serial changes in fluorine-18-fluorodeoxyglucose uptake for veins of interest (ie, popliteal and femoral). Incidence of VTE was assessed for 12 months after lymphoma diagnosis. Results: PET/CT detected a significantly higher inflammatory response in the femoral ( P =0.012) and popliteal ( P =0.013) veins of patients who experienced a VTE event compared with those who remained VTE free in the 12 months after diagnosis. The area under the curve values for receiver operator characteristics analyses were 0.76 (femoral vein) and 0.77 (popliteal vein) based on incidence of VTE occurrence. Univariate analyses demonstrated that PET/CT-derived changes in femoral ( P =0.008) and popliteal ( P =0.002) vein inflammation were significantly associated with VTE-free survival at 12 months after diagnosis. Conclusions: Fluorine-18-fluorodeoxyglucose PET/CT imaging detects treatment-induced venous toxicity that may provide insight into risk of VTE events in pediatric and adolescent and young adult patients with lymphoma.

Partially decellularized tracheal scaffolds have emerged as a potential solution for long-segment tracheal defects. These grafts have exhibited regenerative capacity and the preservation of native mechanical properties resulting from the elimination of all highly immunogenic cell types while sparing weakly immunogenic cartilage. With partial decellularization, new considerations must be made about the viability of preserved chondrocytes. In this study, we propose a multimodal approach for quantifying chondrocyte viability for airway tissue engineering.Tracheal segments (5 mm) were harvested from C57BL/6 mice, and immediately stored in phosphate-buffered saline at -20°C (PBS-20) or biobanked via cryopreservation. Stored and control (fresh) tracheal grafts were implanted as syngeneic tracheal grafts (STG) for 3 months. STG was scanned with micro-computed tomography (μCT) in vivo. STG subjected to different conditions (fresh, PBS-20, or biobanked) were characterized with live/dead assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and von Kossa staining.Live/dead assay detected higher chondrocyte viability in biobanked conditions compared to PBS-20. TUNEL staining indicated that storage conditions did not alter the proportion of apoptotic cells. Biobanking exhibited a lower calcification area than PBS-20 in 3-month post-implanted grafts. Higher radiographic density (Hounsfield units) measured by μCT correlated with more calcification within the tracheal cartilage.We propose a strategy to assess chondrocyte viability that integrates with vivo imaging and histologic techniques, leveraging their respective strengths and weaknesses. These techniques will support the rational design of partially decellularized tracheal scaffolds.N/A Laryngoscope, 2022.

Crayfish (Decapoda: Astacoidea and Parastacoidea) are among the few animals that have stem cells in hemolymph, with the capacity to continuously produce differentiated neuronal structures throughout life. As the use of crayfish and other invertebrates increases in biomedical research, we must develop laboratory standards and guidelines for performing clinical procedures. This manuscript presents introductory protocols for anesthesia in crayfish during diagnostic imaging. Five anesthetic protocols were evaluated: immersion in buffered tricaine methanesulfonate (MS222; 50 mg/L); immersion in buffered MS222 (150 mg/L); immersion in propofol (65 mg/L); injection of propofol (50 mg/kg); and injection of propofol (100 mg/kg) into the ventral surface of an abdominal somite. MS222 immersion (50 and 150 mg/L) had no observable effect on crayfish. After an extended period of time, immersion in propofol (65 mg/L) created a sedative effect suitable for short-term handling. Propofol injection (50 mg/kg) into the ventral surface of an abdominal somite created an effective plane of anesthesia without adverse effects during or after recovery. Propofol injection at 100 mg/kg had adverse effects and is not recommended for use in crayfish. CT imaging was performed successfully as proof of concept for handling anesthetized crayfish. These findings provide initial data for the anesthetization of crayfish used in research settings.

Although the prevalence of obesity in the general population and its perioperative implications among children undergoing inpatient surgeries are well known, little is known about obesity prevalence among children scheduled for ambulatory surgery.Here, we report the trends of obesity and severe obesity among children who underwent ambulatory surgery across multiple centers in the United States and explore the association of obesity status with admission following elective ambulatory surgery.Using data from the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (2012-2019), we selected children 2-18 years old who underwent outpatient surgical procedures under general anesthesia and had documented height, weight, and body mass index (BMI) data. We estimated the prevalence of overweight, obesity (class 1), and severe obesity (class 2 and class 3) patients and explored their association with same-day hospital admission, defined as hospital length of stay ≥1 day.Data from 152 918 children (mean age: 9.7 ± 4.7 years) were analyzed. Of these, 16.4% (n = 25 007) were overweight, 13.8% (n = 21 085) were class 1 obese, 5.2% (n = 7879) were class 2 obese, and 3.0% (n = 4623) were class 3 obese. From 2012 to 2019, class 2 or 3 obesity prevalence increased by 26.7% and 32.5%, respectively. Overweight and obese children had relatively higher odds of same-day hospital admission compared to healthy weight children (overweight odds ratio [95% confidence interval]: 1.05 [1.02, 1.08]; class 1 obesity: 1.04 [1.00, 1.07]; class 2 obesity: 1.09 [1.02, 1.16]; class 3 obesity: 1.20 [1.11, 1.30]).The burden of obesity continues to increase in children scheduled for ambulatory surgery. Children with class 2 and class 3 obesity have higher rates of same-day hospital admission following elective ambulatory surgery compared to healthy weight children, a factor that should be considered in scheduling these patients.

The relationship between preprocedural anxiety and pain is not clear but has the potential to change the way pediatric patients need to be cared for prior to burn procedures. Using results from our recent randomized clinical trial among outpatient burn patients (n = 90) aged 6–17 years, the objective of this subsequent analysis was to assess whether preprocedural anxiety was associated with self-reported and researcher-observed pain scores. Anxiety before the dressing change was assessed using an abbreviated State-Trait Anxiety Inventory for Children (range 6–21) and reported with 95% confidence intervals (CI). Self-reported pain was reported using a Visual Analog Scale (range 0–100) and observed pain was assessed using the Face, Legs, Activity, Cry, and Consolability-revised scale. Over half of patients (58.9%) reported mild anxiety (score < 12) and about 5% of patients reported severe anxiety (score > 16). Younger children (6–8 years) reported higher anxiety scores than older children (15–17 years), but the difference did not achieve statistical significance (mean = 12.7, 95% CI: 11.5 to 13.9, P = .09). Nonparametric spearman correlation indicated that anxiety score was significantly correlated with observed pain (P = .01) and self-reported overall pain neared statistical significance (P = .06). In the final logistic regression of reporting moderate-to-severe pain (pain score > 30), the association between anxiety scores and self-reported overall moderate-to-severe pain was statistically significant (P = .03) when adjusting for race, healing degree, and pain medication use within 6 hr prior to burn dressing care. This pilot study provides preliminary data showing that anxiety before outpatient pediatric burn dressing changes is significantly associated with self-reported overall moderate-to-severe pain.

Introduction: Lymphoma treatment with chemotherapy, alone or in combination with radiation therapy, can have off-target effects that lead to vascular toxicity, which has recently gained attention in the field of cardio-oncology. Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 ( 18 F)-fluorodeoxyglucose (FDG) is standard of care for monitoring lymphoma treatment responses and is a widely accepted tool for assessing vascular inflammation. We hypothesized that 18 F-FDG PET/CT imaging could detect and quantify chemotherapy-induced increases in vascular inflammation following the first cycle of lymphoma treatment in pediatric, adolescent, and young adult (AYA) patients. Methods: Whole-body 18 F-FDG PET/CT images were retrospectively acquired at initial staging of disease and first treatment follow-up for pediatric and AYA lymphoma patients (n=33). Regions of interest were manually drawn using each axial slice of fused PET/CT images for the femoral and popliteal arteries/veins to quantify serial changes in vascular uptake of 18 F-FDG. The changes in the average maximum standard uptake value (SUV max ) for the femoral-popliteal vessels were calculated. Results and Conclusions: The patient population consisted of Non-Hodgkin (55%) and Hodgkin (45%) lymphoma patients with a mean age of 13 years (SD=4.7). 18 F-FDG PET/CT imaging detected ( Fig. 1A ) and quantified a significant increase in the mean SUV max from baseline (0.94±0.03) to first treatment follow-up (1.06±0.02) for the femoral and popliteal arteries/veins ( Fig. 1B ). Standard of care 18 F-FDG PET/CT imaging can non-invasively quantify chemotherapy-induced vascular inflammation in young cancer patients in response to the first cycle of treatment, thus representing an approach for evaluating vascular toxicity and creating novel opportunities for personalized medicine focused on reducing cardiovascular side effects of chemotherapy.

Introduction: Body composition (BC) influences chemotherapy toxicity, surgical complication rates, and overall survival in cancer patients. While recent studies have shown the connection between BC and clinical outcomes in adult oncology populations, BC measures are still often overlooked in the pediatric, adolescent, and young adult (AYA) oncology populations. The objective of this study was to determine the effect of BC on the occurrence of venous thromboembolism (VTE) in pediatric and AYA patients with lymphoma. Methods: Skeletal muscle (SkM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) volumes were manually segmented at vertebral level L3 from 5 consecutive axial CT images ( Fig. 1A ) acquired in a 5-year retrospective cohort of 78 patients with lymphoma (mean age = 13.3 ± 0.6 years). All CT images were acquired at initial staging of disease. Incidence of VTE, including deep vein thrombosis and pulmonary embolism, was evaluated for 12 months after diagnosis. Results and Conclusions: In the first 12 months after diagnosis, 26 of 88 patients (33%) had a VTE event. Patients with VTE had a significantly higher percent of SAT (p = 0.022) and lower percent of SkM (p = 0.036) compared to patients without VTE ( Fig. 1B ). Patients were stratified based on a SkM/SAT cut-off ratio of 0.963, determined using the Receiver-Operating-Characteristic Curve. Patients who were below this SkM/SAT cutoff ratio had a significantly higher probability for VTE in the first 12 months compared to patients who were above the cutoff (log-rank test, p < 0.005) ( Fig. 1C ). This cutoff ratio remained significant after correcting for lymphoma subtype, body mass index, age, and sex using the Cox Proportional-Hazards model. Standard-of-care CT imaging may offer a technique for evaluating BC and predicting outcomes such as VTE in pediatric and AYA patients, thereby offering personalized approaches to cancer care by guiding chemotherapy dosing and nutritional recommendations.

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide

Tissues in the eye are particularly susceptible to oxidative damage due to light exposure. While vitamin C (ascorbic acid) has been noted as a vital antioxidant in the vitreous humor, its physiological concentration (1-2 mM) has been shown to be toxic to retinal and lens epithelial cells inCell viability and reactive oxygen species activity of human retinal and lens epithelial cells treated with various combinations of vitamin C, glutathione, hydrogen peroxide, and a hydrogel vitreous substitute were determined using CellTiter-Glo luminescent cell viability assay and dichlorofluorescein assay, respectively. The vitamin C remaining in hydrogel vitreous substitute or glutathione-vitamin C solutions was determined using a microplate reader at 265 nm wavelength, compared against standard solutions with known concentrations.Glutathione protected the lens and retinal cells from the negative effect of vitamin C on cell viability and prolonged the antioxidant effect of vitamin CThese results indicate glutathione might be an effective addition to vitamin C in intraocular implants, including potential vitreous substitutes, and warrants additional studies on the effectiveness of the vitamin C - glutathione combination in preventing oxidative stress post-vitrectomy.

Research on the vitreous humor and development of hydrogel vitreous substitutes have gained a rapid increase in interest within the past two decades. However, the properties of the vitreous humor and vitreous substitutes have yet to be consolidated. In this paper, the mechanical properties of the vitreous humor and hydrogel vitreous substitutes were systematically reviewed. The number of publications on the vitreous humor and vitreous substitutes over the years, as well as their respective testing conditions and testing techniques were analyzed. The mechanical properties of the human vitreous were found to be most similar to the vitreous of pigs and rabbits. The storage and loss moduli of the hydrogel vitreous substitutes developed were found to be orders of magnitude higher in comparison to the native human vitreous. However, the reported modulus for human vitreous, which was most commonly tested in vitro, has been hypothesized to be different in vivo. Future studies should focus on testing the mechanical properties of the vitreous in situ or in vivo. In addition to its mechanical properties, the vitreous humor has other biotransport mechanisms and biochemical functions that establish a redox balance and maintain an oxygen gradient inside the vitreous chamber to protect intraocular tissues from oxidative damage. Biomimetic hydrogel vitreous substitutes have the potential to provide ophthalmologists with additional avenues for treating and controlling vitreoretinal diseases while preventing complications after vitrectomy. Due to the proximity and interconnectedness of the vitreous humor to other ocular tissues, particularly the lens and the retina, more interest has been placed on understanding the properties of the vitreous humor in recent years. A better understanding of the properties of the vitreous humor will aid in improving the design of biomimetic vitreous substitutes and enhancing intravitreal biotransport.

A cell’s insoluble microenvironment has increasingly been shown to exert influence on its function. In particular, matrix stiffness and adhesiveness strongly impact behaviors such as cell spreading and differentiation, but materials that allow for independent control of these parameters within a fibrous, stromal-like microenvironment are very limited. In the current work, we devise a self-assembling peptide (SAP) system that facilitates user-friendly control of matrix stiffness and RGD (Arg-Gly-Asp) concentration within a hydrogel possessing a microarchitecture similar to stromal extracellular matrix. In this system, the RGD-modified SAP sequence KFE-RGD and the scrambled sequence KFE-R DG can be directly swapped for one another to change RGD concentration at a given matrix stiffness and total peptide concentration. Stiffness is controlled by altering total peptide concentration, and the unmodified base peptide KFE-8 can be included to further increase this stiffness range due to its higher modulus. With this tunable system, we demonstrate that human mesenchymal stem cell morphology and differentiation are influenced by both gel stiffness and the presence of functional cell binding sites in 3D culture. Specifically, cells 24 hours after encapsulation were only able to spread out in stiffer matrices containing KFE-RGD. Upon addition of soluble adipogenic factors, soft gels facilitated the greatest adipogenesis as determined by the presence of lipid vacuoles and PPARγ-2 expression, while increasing KFE-RGD concentration at a given stiffness had a negative effect on adipogenesis. This three-component hydrogel system thus allows for systematic investigation of matrix stiffness and RGD concentration on cell behavior within a fibrous, three-dimensional matrix. Statement of Significance Physical cues from a cell’s surrounding environment—such as the density of cell binding sites and the stiffness of the surrounding material—are increasingly being recognized as key regulators of cell function. Currently, most synthetic biomaterials used to independently tune these parameters lack the fibrous structure characteristic of stromal extracellular matrix, which can be important to cells naturally residing within stromal tissues. In this manuscript, we describe a 3D hydrogel encapsulation system that provides user-friendly control over matrix stiffness and binding site concentration within the context of a stromal-like microarchitecture. Binding site concentration and gel stiffness both influenced cell spreading and differentiation, highlighting the utility of this system to study the independent effects of these material properties on cell function.

This study investigates whether the presence of accommodative tissues biomechanically influences the shape of the cornea and potentially drives corneal morphogenesis during embryonic ocular development. Porcine eyes were subjected to an internal pressure simulating intraocular pressure. Ocular geometry was evaluated using a corneal topographer and digital cameras before and after dissection of the accommodative tissues. A computational model of the porcine eye was constructed and loaded by an internal pressure representing intraocular pressure. Eye shape was evaluated in models with and without the ciliary body. The porcine model was generalized to the human model, simplified model, or embryonic model with different ocular tissue shapes, sizes, and stiffnesses. Experimental data showed that, even in the six-month-old pig eye, the average corneal radius of curvature increased after the removal of accommodative tissues compared to sham controls (p = 0.002). Computational results agreed with the experimental data and further suggested that the change in corneal radius is greater when the tissue stiffness is low and the intraocular pressure is high, regardless of the geometry and size of the eye components. Using a combined in vitro and in silico approach, this study explores the biomechanical influence of the accommodative tissues and related loads on the cornea and offers additional factors that might influence the shape of the cornea.

Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small-gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post-vitrectomy cataract formation and reduce the cost of additional surgeries.