Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period,a Single-Center Observational Study

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.     

Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.     

Plasma Free Fatty Acids and Metabolic Effect in Type 2 Diabetes,an Ancillary Study from a Randomized Clinical Trial

Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias. Pentadecanoic acid, heptadecanoic acid and trans-palmitoleic acid are fatty acids that are not synthesized endogenously but are obtained from the diet, particularly dairy, making them reasonable biomarkers of dairy consumption. We investigated the association of dairy fatty acid biomarkers with glycated hemoglobin (HbA1c) and cardiovascular risk factors in type 2 diabetes (T2D). In a clinical trial, 111 participants with T2D (age 58.5 ± 8.9 years, HbA1c 8.09 ± 0.96%) were randomized into three groups: a control group that maintained baseline dairy intake, a low-fat (LF) group that incorporated ≥3 servings/day of LF dairy and a high-fat (HF) group that incorporated ≥3 servings/day of HF dairy. We compared the fatty acids (FA) composition between the three groups at 24 weeks. Pentadecanoic acid and trans-palmitoleic acid increased in the HF group by 14.1% ± 5.4% and 17.5% ± 5.1%, respectively, but not in the control and LF groups (p = 0.0474 and p = 0.0025 for group-by-time interaction, respectively). Those increases were positively associated with changes in total cholesterol, very-low-density lipoprotein cholesterol VLDL-C and triglycerides but were not associated with changes in HbA1c from baseline to 24 weeks. These results suggest that the intervention was successful and that participants were likely compliant, which supports the validity of the main trial.     

A novel approach to delivery of extracorporeal support using a modified continuous flow ventricular assist device in a mid‐volume congenital heart program

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device—based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty‐seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device‐based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.     

Are We Being Fooled by Fluoroscopy? Distortion May Affect Limb-Length Measurements in Direct Anterior Total Hip Arthroplasty

BackgroundDistortion is an intrinsic phenomenon associated with image-intensified fluoroscopy that is both poorly understood and infrequently appreciated by orthopedic surgeons. Little information exists regarding its potential influence on intraoperative parameters during orthopedic surgery, let alone during direct anterior (DA) total hip arthroplasty (THA). The purpose of this study was to quantify the amount of potential error caused by fluoroscopic distortion during DA THA.MethodsIntra-operative fluoroscopic pelvic images from 74 DA THAs were reviewed by two independent readers. All images were obtained using the same fluoroscopic C-arm unit with a radiopaque grid attached to the image intensifier. The vertical distortion from a straight central horizontal line at the peripheries of images were measured and summed to yield the combined vertical distortion similar to how a surgeon calculates a side to side comparison of limb lengths. Simple linear regression was used to evaluate associations between total distortion and patient demographics, operating theaters, and various operative parameters.ResultsThe average combined distortion was 10.0mm (range 2.0-20.0mm). There was a significant difference in the average distortion observed in different theaters (P < .001). There was no association between distortion and patient demographics or fluoroscopic time (all, P > .05).ConclusionFluoroscopic distortion is unpredictable and can cause a substantial amount of error when comparing limb lengths during DA THA. This is a critical finding as this amount of inaccuracy could lead to unintended implant positioning and limb-length discrepancies if unaccounted for.     

High Rates of Spacer Fracture in the Setting of Extended Trochanteric Osteotomy With a Specific Thin-Core Articulating Antibiotic Hip Spacer

BackgroundTwo-stage revision remains the standard of care for prosthetic joint infection after total hip arthroplasty. However, there are substantial complications associated with articulating antibiotic hip spacers. Handmade and molded spacers have been shown to have higher rates of spacer fracture than antibiotic-coated prostheses (ACPs). The aim of this study is to review outcomes with an implant that is often categorized as an ACP spacer, the Zimmer-Biomet StageOne Select Femoral Spacer (ZBSO).MethodsA retrospective review was performed of 63 patients who underwent placement of a ZBSO. Patients were compared based on whether or not an extended trochanteric osteotomy (ETO) was performed using Fisher’s exact and t-tests.ResultsFive patients were excluded due to lack of follow-up or death shortly after stage 1 surgery, leaving 58 patients. Spacer fracture was noted in 5 of 58 patients (8.6%). Sixteen patients underwent ETO and 25.0% suffered a spacer fracture compared to 2.3% without ETO (odds ratio 13.7, P = .0248). There was no association between patient demographics or ETO length and spacer fracture. Two patients had periprosthetic fractures (3.4%) and 4 had dislocations (6.9%). Forty-nine patients (84.4%) went on to second-stage revision; of those 26.5% failed to clear the infection and required an average of 2.2 additional surgeries.ConclusionThe ZBSO spacer has overall complication rates similar to previously reported spacer series. Although the ZBSO looks like an ACP spacer, in the setting of ETO, it behaves like a molded or handmade spacer with a high rate of spacer fracture (25%) due to the small diameter of the core. This implant should be used with caution in combination with an ETO.     

Pig kidney xenotransplantation: Progress toward clinical trials

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.     

Pediatric snow sport injuries differ by age

BackgroundUnintentional injury is the leading cause of death among pediatric patients. There were 13,436 injuries related to snow sports in those younger than 15 in 2015, with 4.8% requiring admission. These sports are high-risk given the potential for injury even when using protective equipment. We hypothesized that snow sport injury patterns would differ based on patient age.MethodsA cross-sectional analysis of the 2009 and 2012 Kids' Inpatient Database was performed.Cases of injuries were identified and analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was used to assess for confounders.ResultsWithin 745 admissions, there was a statistically significant decrease in skull/facial fractures with increasing age and a statistically significant increase in abdominal injuries with increasing age. Children in early and middle childhood were at increased odds of being hospitalized with skull/facial fractures, while older children were more likely hospitalized with abdominal injuries.ConclusionsWithin the pediatric snow sport population, younger children are more likely to experience head injuries, while older children are more likely to experience abdominal injuries.Further research is needed to determine the origin of this difference, and continued legislation on helmets is also necessary in reducing intracranial injuries.Level of EvidenceIII