Ultrasound Investigation of the Fifth Intercostal Space Landmark for Chest Tube Thoracostomy Site Selection in Pediatric Patients.

OBJECTIVES: Chest tube thoracostomy site selection is typically chosen through landmark identification of the fifth intercostal space (ICS). Using point-of-care ultrasound (POCUS), studies have shown this site to be potentially unsafe in many adults; however, no study has evaluated this in children. The primary aim of this study was to evaluate the safety of the fifth ICS for pediatric chest tube placement, with the secondary aim to identify patient factors that correlate with an unsafe fifth ICS. METHODS: This was an observational study using POCUS to evaluate the safety of the fifth ICS for chest tube thoracostomy placement using a convenience sample of pediatric emergency department patients. Safety was defined as the absence of the diaphragm appearing within or above the fifth ICS during either tidal or maximal respiration. Univariate and multivariable analyses were used to identify patient factors that correlated with an unsafe fifth ICS. RESULTS: Among all patients, 10.3% (95% confidence interval [CI] 6.45-16.1) of diaphragm measurements crossed into or above the fifth ICS during tidal respiration and 27.2% (95% CI 19.0-37.3) during maximal respiration. The diaphragm crossed the fifth ICS more frequently on the right when compared with the left, with an overall rate of 45.0% (95% CI 36.1-54.3) of right diaphragms crossing during maximal respiration. In both univariate and multivariate analyses, a 1-kg/m2 increase in body mass index was associated with an increase of 10% or more in the odds of crossing during both tidal and maximal respiration (P = 0.003 or less). CONCLUSIONS: A significant number of pediatric patients have diaphragms that cross into or above the fifth ICS, suggesting that placement of a chest tube thoracostomy at this site would pose a significant complication risk. POCUS can quickly and accurately identify these unsafe sites, and we recommend it be used before pediatric chest tube thoracostomy.

The Current State of Advanced Pediatric Emergency Medicine Point-of-Care Ultrasound (POCUS) Training: Exploring Recent POCUS Fellowship Application Trends and Alternate Training Models.

OBJECTIVES: This study aims to assess the current state of advanced pediatric emergency medicine (PEM) point-of-care ultrasound (POCUS) training in North America, including trends in dedicated PEM POCUS fellowships and alternative advanced POCUS training pathways, to better guide future educational efforts within the field. METHODS: We identified and surveyed 22 PEM POCUS fellowship directors across the United States and Canada regarding PEM POCUS fellowship application trends, potential barriers to pursuing additional POCUS training, and novel training models that meet the needs of the PEM POCUS workforce. RESULTS: The past 5 years have seen a growth in both PEM POCUS fellowship program number and trainee positions available, with a general impression by fellowship directors of a high demand for faculty who have these training credentials. However, there was a discordant drop in fellowship applicants and corresponding match rate in 2022, the cause of which is not clear. A number of programs are offering alternative advanced training options including combined PEM/POCUS fellowships and POCUS tracks within PEM fellowship. CONCLUSION: As POCUS use within PEM evolves, a growing number of advanced training options are being developed. Understanding the motivations and barriers for pursuing advanced POCUS training can help to shape these options going forward, to ensure the experience incorporated within each model meets the needs of trainees, the needs of PEM divisions, and the future needs of our field.

Pediatric Emergency Medicine Ultrasound Fellowship Programs.

Point of care ultrasound (POCUS) has undergone important growth in the field of Pediatric Emergency Medicine (PEM) in the last 14 years and is recognized as a critical diagnostic tool in the care of ill and injured children. The first PEM POCUS fellowship was established in 2010. Now, there are currently 30 ultrasound fellowships that offer training to PEM physicians. In 2014, 46 PEM POCUS leaders established the P2 (PEM POCUS) Network (www.P2network.org). This serves as a platform for sharing expertise, building research collaborations, and offering mentorship in the use of POCUS in PEM. In 2019, a multinational group of experts in PEM POCUS published the first consensus guidelines for prioritizing core applications of POCUS, which are fundamental to PEM fellowship training 1. In 2022, the international research priorities for PEM POCUS were published 2. In the same year, the development of a consensus-based definition of focused assessment with sonography for trauma (FAST) in children was established 3.

Point-of-Care Ultrasound-Guided Arthrocentesis of a Pediatric Septic Ankle.

ABSTRACT: Septic arthritis is one potential cause of pediatric joint effusion and pain that may lead to significant morbidity. We present a case where point-of-care ultrasound was used to identify and aspirate a joint effusion in a pediatric patient with septic arthritis of the ankle, facilitating timely diagnosis and care. We review the technique for arthrocentesis of the ankle and literature on point-of-care ultrasound in the diagnosis of pediatric septic arthritis.

Ultrasound-Guided Paravenous Saphenous Nerve Block for Lower Extremity Abscess Incision and Drainage in a Male Adolescent.

ABSTRACT: The use of ultrasound-guided regional anesthesia is growing as a modality for analgesia provision within the pediatric emergency department. We present a case in which a paravenous saphenous nerve block was used for anesthesia during incision and drainage of a lower extremity abscess. We further review the technique and literature concerning this straightforward and effective procedure.

Esophageal Bougienage for Management of Lodged Esophageal Coins: Safe, Effective, Efficient, and Underused.

OBJECTIVES: The aims of the study are to evaluate outcomes of esophageal bougienage for management of lodged esophageal coins and to assess the extent of bougienage usage and barriers among emergency providers. METHODS: We performed a retrospective chart review of pediatric patients with single lodged esophageal coins presenting to our single academic pediatric emergency department between November 2012 and December 2018. We compared procedural outcomes, complications, length of stay (LOS), and cost between those managed with bougienage and with endoscopy. We further surveyed emergency physicians to assess the extent of bougienage usage and barriers to utilization across different institutions. RESULTS: We identified 205 patients with single lodged esophageal coins presenting during our study window. One hundred forty-seven patients ultimately underwent bougienage with 97% success and no major complications. Fifty-six patients were managed by endoscopy with 100% success and one major complication. Bougienage had significantly lower LOS (median 2.18 vs 11.92 hours, P < 0.001) and hospital charges (median $3533 vs $12,679, P < 0.001) compared with endoscopy. We received 242 completed surveys representing 38 states from primarily academic pediatric emergency physicians. The majority of respondents (90%) used specialist consult with only 4.5% performing bougienage. A total of 36.4% of respondents had never heard of the procedure and only 16.1% had ever performed it. Barriers to usage included lack of provider training (95.6%), perceived risk of complications (94.4%), and perceived lack of success (80.5%). CONCLUSIONS: Bougienage is safe and effective with significant LOS and cost benefits compared with endoscopy. Despite these advantages, the procedure is underused, because of lack of provider education and concerns regarding safety, efficacy, and both family and specialist preference, which are not supported by current literature. These data support the need for broader education regarding the bougienage technique, as well as larger prospective studies of its safety and outcomes.

Establishing the international research priorities for pediatric emergency medicine point-of-care ultrasound: A modified Delphi study.

BACKGROUND: The Pediatric Emergency Medicine (PEM) Point-of-care Ultrasound (POCUS) Network (P2Network) was established in 2014 to provide a platform for international collaboration among experts, including multicenter research. The objective of this study was to use expert consensus to identify and prioritize PEM POCUS topics, to inform future collaborative multicenter research. METHODS: Online surveys were administered in a two-stage, modified Delphi study. A steering committee of 16 PEM POCUS experts was identified within the P2Network, with representation from the United States, Canada, Italy, and Australia. We solicited the participation of international PEM POCUS experts through professional society mailing lists, research networks, social media, and "word of mouth." After each round, responses were refined by the steering committee before being reissued to participants to determine the ranking of all the research questions based on means and to identify the high-level consensus topics. The final stage was a modified Hanlon process of prioritization round (HPP), which emphasized relevance, impact, and feasibility. RESULTS: Fifty-four eligible participants (16.6%) provided 191 items to Survey 1 (Round 1). These were refined and consolidated into 52 research questions by the steering committee. These were issued for rating in Survey 2 (Round 2), which had 45 participants. At the completion of Round 2, all questions were ranked with six research questions reaching high-level consensus. Thirty-one research questions with mean ratings above neutral were selected for the HPP round. Highly ranked topics included clinical applications of POCUS to evaluate and manage children with shock, cardiac arrest, thoracoabdominal trauma, suspected cardiac failure, atraumatic limp, and intussusception. CONCLUSIONS: This consensus study has established a research agenda to inform future international multicenter PEM POCUS trials. This study has highlighted the ongoing need for high-quality evidence for PEM POCUS applications to guide clinical practice.

Diagnosis of Internal Jugular Vein Septic Thrombophlebitis by Point-of-Care Ultrasound.

ABSTRACT: Septic thrombophlebitis represents a rare but serious collection of diseases, which carry a high risk of morbidity and mortality requiring prompt and aggressive treatment. Diagnosis centers on identification of thrombus along with clinical and microbiologic data. We present a case where point-of-care ultrasound was used to diagnose septic thrombophlebitis of the internal jugular vein and expedite appropriate therapy. We further review the technique and literature for ultrasound diagnosis of venous thrombosis and associated thrombophlebitis.

Point-of-Care Ultrasound to Assess Gastric Content in Pediatric Emergency Department Procedural Sedation Patients.

OBJECTIVES: There is debate regarding the timing of procedural sedation and analgesia (PSA) in relation to fasting status. Point-of-care ultrasound (POCUS) provides the ability to measure gastric content and is being used as a surrogate for aspiration risk in anesthesia. We sought to evaluate the gastric content of pediatric emergency department (PED) patients undergoing PSA using POCUS. METHODS: We performed a prospective observational study using a convenience sample of pediatric patients undergoing PSA between July 1, 2018, and June 30, 2019. Following a brief history, gastric content was measured using POCUS in both supine and right lateral decubitus positions at 2-hour intervals until the time of PSA. Qualitative content and calculated volume were classified based on the Perlas Model of anesthesia "Risk" assessment. RESULTS: Ninety-three patients were enrolled with 61.3% male and mean age of 6.5 years. Gastric content was determined in 92 patients. There were 79.3% that had "high risk" content at the time of PSA, with a median fasting time of 6.25 hours and no serious adverse events. Fasting duration had a weak to moderate ability to predict "risk" category (area under the curve = 0.73), with no patient (n = 17) who underwent multiple evaluations awaiting PSA progressing from "high" to "low risk." CONCLUSIONS: The majority of PED patients undergoing PSA at our institution had "high risk" gastric content with no clinically significant change occurring during serial evaluations. This calls into question the utility of delaying PSA based upon fasting status and lends support to a more comprehensive risk-benefit approach when planning pediatric PSA.

Point-of-Care Ultrasound Facilitates Management of Ruptured Ectopic Pregnancy.

ABSTRACT: Abdominal pain in the pregnant adolescent presents a diagnostic dilemma with potential life-threatening etiologies. We present a case where point-of-care ultrasound was used to facilitate diagnosis and expedite lifesaving management of a ruptured ectopic pregnancy. We further review the technique and literature for first-trimester transabdominal point-of-care ultrasound.

Ultrasound-Guided Posterior Tibial Nerve Block for Plantar Foot Foreign Body Removal.

Ultrasound-guided regional anesthesia is a growing modality within the pediatric emergency department. Here we present a case where a posterior tibial nerve block was used for anesthesia during foreign body removal from the plantar foot. We further review the technique and literature regarding this straightforward and highly effective procedure.

Point-of-Care Ultrasound to Assess Gastric Content.

Gastric ultrasound (US) is a growing modality within the point-of-care ultrasound (POCUS) field. It provides the ability to directly measure an individual patient's gastric content and has potential use as both a clinical and a research tool. Here, we review the historical development of current gastric US models and their clinical application within the field of general anesthesia, describe the US findings and technique for using POCUS to assess gastric content, and discuss the current and potential applications of gastric POCUS within the emergency department.

In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolor" images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange saturation transfer liposomes form an attractive novel platform for multicolor imaging in vivo.

Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide.

microRNA (miRNA) are small non-coding RNA targeting mRNAs leading to their instability and diminished translation. Altered expression of miRNA is associated with cancer. Inflammation and nitric oxide modulates the development of lymphomas in p53 knockout mice and there exists a negative feedback loop between p53 and NOS2. Using a genetic strategy, we tested the hypothesis that inflammation-induced oxidative and nitrosative stress modulates miRNA expression in mouse model deficient in either p53 or NOS2. Mice treated with Corynebacterium parvum (C. parvum), to induce inflammation, clearly separated from controls by their miRNA profiles in wild-type, p53- and NOS2-knockout genetic backgrounds. C. parvum-induced inflammation significantly (p < 0.005) increased miR-21, miR-29b and miR-34a/b/c and decreased (p < 0.005) mir-29c and mir-181a/c expression in the spleen of C57BL mice. However, p53-knockout C57BL mice did not show a significant increase in the mir-34b/c or a decrease in mir-29c expression following C. parvum-induced inflammation. Expression of mir-21, mir-29b and mir-181a was independent of p53-status. NOS2-knockout C57BL mice showed a significant increase in miR-21 and miR-34a/b/c and decrease in miR-181a similar to the wild-type (WT) mice following C. parvum-induced inflammation. However, in contrast to the WT mice, miR-29b/c expression was not affected following C. parvum-induced inflammation in NOS2 knockout mice. N-acetyl cysteine, an anti-oxidant, reduced the expression of miR-21 and miR-29b in C. parvum-treated WT mice (p < 0.005) as compared with control C. parvum-treated mice. These data are consistent with the hypothesis that inflammation modulates miRNA expression in vivo and the alteration in specific miRNA under an inflammatory microenvironment, can be influenced by p53 (miR-34b/c) and NO(•) (29b/c).

Comprehensive Review of Patulin Control Methods in Foods.

The mycotoxin, patulin (4-hydroxy-4H-furo [3, 2c] pyran-2[6H]-one), is produced by a number of fungi common to fruit- and vegetable-based products, most notably apples. Despite patulin's original discovery as an antibiotic, it has come under heavy scrutiny for its potential negative health effects. Studies investigating these health effects have proved inconclusive, but there is little doubt as to the potential danger inherent in the contamination of food products by patulin. The danger posed by patulin necessitates its control and removal from foods products, creating a demand for handling and processing techniques capable of doing so, preferably at low cost to industry. With this being the case, much research has been devoted to understanding the basic chemical and biological nature of patulin, as well as its interaction within foods and food production. While past resarch has elucidated a great deal, patulin contamination continues to be a challenge for athe food industry. Here, we review in depth the past research on patulin with an emphasis upon its influence within the food industry, including its regulation, health effects, biosynthesis, detection, quantification, distribution within foods, and control, during the various stages of apple juice production. Finally, key areas where future patulin research should focus to best control the patulin contamination problem within the food industry are addressed.

p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis.

p53-mediated apoptosis may involve the induction of redox-controlling genes, resulting in the production of reactive oxygen species. Microarray expression analysis of doxorubicin exposed, related human lymphoblasts, p53 wild-type (WT) Tk6, and p53 mutant WTK1 identified the p53-dependent up-regulation of manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx). Consensus p53 binding sequences were identified in human MnSOD and GPx promoter regions. A 3-fold increase in the MnSOD promoter activity was observed after the induction of p53 in Li-Fraumeni syndrome (LFS) fibroblast, TR9-7, expressing p53 under the control of a tetracycline-regulated promoter. An increased protein expression of endogenous MnSOD and GPx also positively correlated with the level of p53 induction in TR9-7 cells. However, catalase (CAT) protein expression remained unaltered after p53 induction. We also examined the expression of MnSOD, GPx, and CAT in a panel of normal or LFS fibroblasts, containing either WT or mutant p53. We found increased MnSOD enzymatic activity, MnSOD mRNA expression, and MnSOD and GPx protein in LFS fibroblasts carrying a WT p53 allele when compared with homozygous mutant p53 isogenic cells. The CAT protein level was unchanged in these cells. We observed both the release of cytochrome C and Ca(2+) from the mitochondria into the cytoplasm and an increased frequency of apoptotic cells after p53 induction in the TR9-7 cells that coincided with an increased expression of MnSOD and GPx, and the level of reactive oxygen species. The increase in apoptosis was reduced by the antioxidant N-acetylcysteine. These results identify a novel mechanism of p53-dependent apoptosis in which p53-mediated up-regulation of MnSOD and GPx, but not CAT, produces an imbalance in antioxidant enzymes and oxidative stress.

Improved protection of rhesus macaques against intrarectal simian immunodeficiency virus SIV(mac251) challenge by a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen.

In this study we investigated the ability of a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen to induce protective immunity in rhesus macaques against pathogenic simian immunodeficiency virus(mac251). Immunization of macaques by two sequential administrations of the same recombinants by the same route resulted in boosting and persistence of SIV-specific cellular immune responses for 42 weeks past the initial immunization. Anti-SIV gp120 immunoglobulin G (IgG) and IgA antibodies were induced in secretory fluids, and all macaques exhibited serum neutralizing antibody activity. After intrarectal SIV(mac251) challenge, all of the macaques became infected. However, relative protection, as assessed by statistically significant lower SIV viral loads in plasma at both acute infection and set point, was observed in 8 out of 12 immunized non-Mamu-A(*)01 animals. Elevated mean cellular immune responses to Gag and Env, neutralizing antibody activity, and IgG and IgA binding antibody levels were observed in the eight protected macaques. Statistically significant correlations with protective outcome were observed for cellular immune responses to SIV Env and Gag and for SIV gp120-specific IgG antibodies in nasal and vaginal fluids. Two macaques that exhibited the greatest and most persistent viremia control also exhibited strong CD8(+) T-cell antiviral activity. The results suggest that a spectrum of immune responses may be necessary for adequate control of viral replication and disease progression and highlight a potential role for nonneutralizing antibodies at mucosal sites.

Isolation, structural characterization, and properties of mattacin (polymyxin M), a cyclic peptide antibiotic produced by Paenibacillus kobensis M.

Mattacin is a nonribosomally synthesized, decapeptide antibiotic produced by Paenibacillus kobensis M. The producing strain was isolated from a soil/manure sample and identified using 16 S rRNA sequence homology along with chemical and morphological characterization. An efficient production and isolation procedure was developed to afford pure mattacin. Structure elucidation using a combination of chemical degradation, multidimensional NMR studies (COSY, HMBC, HMQC, ROESY), and mass spectrometric (MALDI MS/MS) analyses showed that mattacin is identical to polymyxin M, an uncommon antibiotic reported previously in certain Bacillus species by Russian investigators. Mattacin (polymyxin M) is cyclic and possesses an amide linkage between the C-terminal threonine and the side chain amino group of the diaminobutyric acid residue at position 4. It contains an (S)-6-methyloctanoic acid moiety attached as an amide at the N-terminal amino group, one D-leucine, six L-alpha,gamma-diaminobutyric acid, and three L-threonine residues. Transfer NOE experiments on the conformational preferences of mattacin when bound to lipid A and microcalorimetry studies on binding to lipopolysaccharide showed that its behavior was very similar to that observed in previous studies of polymyxin B (a commercial antibiotic), suggesting an identical mechanism of action. It was capable of inhibiting the growth of a wide variety of Gram-positive and Gram-negative bacteria, including several human and plant pathogens with activity comparable with purified polymyxin B. The biosynthesis of mattacin was also examined briefly using transpositional mutagenesis by which 10 production mutants were obtained, revealing a set of genes involved in production.