Jason A. Levy

Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle

Biologists have long been concerned about what constrains variation in cell size, but progress in this field has been slow and stymied by experimental limitations. Here we describe a new method, ergodic rate analysis (ERA), that uses single-cell measurements of fixed steady-state populations to accurately infer the rates of molecular events, including rates of cell growth. ERA exploits the fact that the number of cells in a particular state is related to the average transit time through that state. With this method, it is possible to calculate full time trajectories of any feature that can be labelled in fixed cells, for example levels of phosphoproteins or total cellular mass. Using ERA we find evidence for a size-discriminatory process at the G1/S transition that acts to decrease cell-to-cell size variation.

Bedside ultrasound in pediatric emergency medicine.

Bedside emergency ultrasound has been used by emergency physicians for >20 years for a variety of conditions. In adult centers, emergency ultrasound is routinely used in the management of victims of blunt abdominal trauma, in patients with abdominal aortic aneurysm and biliary disease, and in women with first-trimester pregnancy complications. Although its use has grown dramatically in the last decade in adult emergency departments, only recently has this tool been embraced by pediatric emergency physicians. As the modality advances and becomes more available, it will be important for primary care pediatricians to understand its uses and limitations and to ensure that pediatric emergency physicians have access to the proper training, equipment, and experience. This article is meant to review the current literature relating to emergency ultrasound in pediatric emergency medicine, as well as to describe potential pediatric applications.

Pediatric Emergency Medicine Fellow Training in Ultrasound: Consensus Educational Guidelines

The importance of point-of-care emergency ultrasound (EUS) to the practice of emergency medicine (EM) is well established, and mounting research continues to demonstrate how EUS can benefit pediatric emergency department (ED) patients. As members of the EM community, pediatric EM (PEM) physicians should understand the potential value of EUS and seek opportunities to incorporate EUS into their daily practice. Currently, EUS education and training is at an early developmental stage for PEM fellows and varies greatly between programs. The goal of this article is to provide consensus education guidelines and to describe a sample curriculum that can be used by PEM fellowship programs when developing or revising their US training curricula. The authors recognize that programs may be at different stages of EUS development and will consequently need to tailor curricula to individual institutional needs and capabilities. This guideline was developed through a collaborative process between EUS educators and members of the American Academy of Pediatrics Section of EM Fellowship Directors Subcommittee. The guideline includes the following topics: important considerations regarding EUS in PEM, PEM US program framework, PEM US curriculum, PEM US education program, and competency assessment.

Effect of Reduction in the Use of Computed Tomography on Clinical Outcomes of Appendicitis

IMPORTANCE Advanced diagnostic imaging is commonly used in the evaluation of suspected appendicitis in children. Despite its inferior diagnostic performance, ultrasonography (US) is now preferred to computed tomography (CT) owing to concerns about ionizing radiation exposure. With changes in imaging modalities, the influence on outcomes should be assessed. OBJECTIVES To review trends in the use of US and CT for children with appendicitis and to investigate simultaneous changes in the proportions of negative appendectomy, appendiceal perforation, and emergency department (ED) revisits. DESIGN, SETTING, AND PARTICIPANTS We reviewed the Pediatric Health Information System administrative database for children who presented to the ED with the diagnosis of appendicitis or who underwent an appendectomy in 35 US pediatric institutions from January 1, 2010, through December 31, 2013. MAIN OUTCOMES AND MEASURES We studied the use of US and CT for trends and their association with negative appendectomy, appendiceal perforation, and 3-day ED revisits. RESULTS Our investigation included 52,153 children with appendicitis. Use of US increased 46% (from 24.0% in 2010 to 35.3% in 2013; absolute difference, 11.3%; adjusted test for linear trend, P = .02), whereas use of CT decreased 48% (from 21.4% in 2010 to 11.6% in 2013; absolute difference, -9.8%; adjusted test for linear trend, P < .001). The proportion of negative appendectomy declined during the 4-year study period from 4.7% in 2010 to 3.6% in 2013 (test for linear trend, P = .002), whereas the proportion of perforations (32.3% in 2010 to 31.9% in 2013) and ED revisits (5.6% in 2010 and 2013) did not change (adjusted tests for linear trend, P = .64 and P = .84, respectively). CONCLUSIONS AND RELEVANCE Among children with suspected appendicitis, the use of US imaging has increased substantially as the use of CT has declined. Despite the increased reliance on the diagnostically inferior US, important condition-specific quality measures, including the frequency of appendiceal perforation and ED revisits, remained stable, and the proportion of negative appendectomy declined slightly.

Bedside ultrasound in the pediatric emergency department

Purpose of review Emergency bedside ultrasound has been used by emergency and critical care physicians for over two decades. Its use has grown rapidly in emergency medicine and the range of diagnostic and procedural applications has continued to expand; only recently, however, has this tool been embraced by pediatric emergency and critical care physicians. As this technology develops and becomes more available pediatricians should understand its uses and limitations. Recent findings Use of emergency bedside ultrasound for victims of trauma and for procedural applications such as central venous access are well established in adults. Recent published studies suggest that utilizing bedside ultrasound for these purposes may be beneficial in pediatric emergency medicine. Other reports portend future pediatric applications such as assessment of volume status and dehydration, fracture identification and reduction, and aiding in the performance of lumbar punctures. Summary In a review of the literature, it is clear that emergency bedside ultrasound has a role in pediatric emergency and critical care medicine. Much more research is needed, however, to determine which sonographic assessments are of the greatest value. Collaborative efforts will likely be needed to establish definitive applications.

Advances in point-of-care ultrasound in pediatric emergency medicine.

Purpose of review Point-of-care ultrasound (POCUS) has become an integral part of emergency medicine practice. Research evaluating POCUS in the care of pediatric patients has improved the understanding of its potential role in clinical care. Recent findings Recent work has investigated the ability of pediatric emergency medicine (PEM) physicians to perform a wide array of diagnostic and procedural applications in POCUS ultrasound. Studies have demonstrated that PEM providers are able to identify an array of diseases, including intussusception, pyloric stenosis and appendicitis. Novel applications of ultrasound, such as a cardiac evaluation in the acutely ill patient or identification of skull fractures in the assessment of a patient with head injury, have shown excellent promise in recent studies. These novel applications have the potential to reshape pediatric diagnostic algorithms. Summary Key applications in PEM have been investigated in the recent publications. Further exploration of the ability to integrate ultrasound into routine practice will require larger-scale studies and continued growth of education in the field. The use of ultrasound in clinical practice has the potential to improve safety and efficiency of care in the pediatric emergency department.

Determining the Feasibility of Managing Erectile Dysfunction in Humans With Placental-Derived Stem Cells.

INTRODUCTION Stem cell therapy is thought to improve wound healing and promote vasculogenesis and has also been investigated as a treatment for patients with erectile dysfunction (ED), which is usually caused by a microvascular disease such as diabetes mellitus or hypertension. OBJECTIVE To determine the feasibility and effects of using placental matrix-derived mesenchymal stem cells (PM-MSCs) in the treatment of patients with ED. METHODS Participants were recruited from a private practice urology in Coral Springs, Florida. Each patient received an injection of PM-MSCs and was followed up with at 6 weeks, 3 months, and 6 months to assess peak systolic velocity (PSV), end diastolic velocity, stretched penile length, penile width, and erectile function status based on the International Index of Erectile Function questionnaire. RESULTS Eight patients were injected with PM-MSCs. At the 6-week follow-up, PSV ranged from 25.5 cm/s to 56.5 cm/s; at 3 months, PSV ranged from 32.5 cm/s to 66.7 cm/s. Using unpaired t tests, the increase in PSV was statistically significant (P<.05). At 6 months, PSV ranged from 50.7 cm/s to 73.9 cm/s (P<.01). Changes in measured end diastolic velocity, stretched penile length, penile width, and International Index of Erectile Function scores were not statistically significant. At the 6-week follow-up, 2 patients for whom previous oral therapies failed had the ability to sustain erections on their own. At the 3-month follow-up, 1 additional patient was able to achieve erections on his own. CONCLUSION To our knowledge, this is one of the first human studies to report on the feasibility of using stem cell therapy to treat patients with ED. The results indicate that this treatment may be beneficial, and further investigations with larger sample sizes should be conducted. (ClinicalTrials.gov number NCT02398370).

Point-of-Care Ultrasonography by Pediatric Emergency Physicians

Point-of-care ultrasonography is increasingly being used to facilitate accurate and timely diagnoses and to guide procedures. It is important for pediatric emergency physicians caring for patients in the emergency department to receive adequate and continued point-of-care ultrasonography training for those indications used in their practice setting. Emergency departments should have credentialing and quality assurance programs. Pediatric emergency medicine fellowships should provide appropriate training to physician trainees. Hospitals should provide privileges to physicians who demonstrate competency in point-of-care ultrasonography. Ongoing research will provide the necessary measures to define the optimal training and competency assessment standards. Requirements for credentialing and hospital privileges will vary and will be specific to individual departments and hospitals. As more physicians are trained and more research is completed, there should be one national standard for credentialing and privileging in point-of-care ultrasonography for pediatric emergency physicians.

Intravenous dextrose for children with gastroenteritis and dehydration: a double-blind randomized controlled trial.

STUDY OBJECTIVE We seek to determine whether an initial intravenous bolus of 5% dextrose in normal saline solution compared with normal saline solution will lead to a lower proportion of hospitalized patients and a greater reduction in serum ketone levels in children with gastroenteritis and dehydration. METHODS We enrolled children aged 6 months to 6 years in a double-blind, randomized controlled trial of patients presenting to a pediatric emergency department. Subjects were randomized to receive a 20 mL/kg infusion of either 5% dextrose in normal saline solution or normal saline solution. Serum ketone levels were measured before and at 1- and 2-hour intervals after the initial study fluid bolus administration. Primary outcome was the proportion of children hospitalized. Secondary outcome was change in serum ketone levels over time. RESULTS One hundred eighty-eight children were enrolled. The proportion of children hospitalized did not differ between groups (35% in the 5% dextrose in normal saline solution group versus 44% in the normal saline solution group; risk difference 9%; 95% confidence interval [CI] -5% to 22%). Compared with children who received normal saline solution, those who received 5% dextrose in normal saline solution had a greater reduction in mean serum ketone levels at both 1 hour (mean Δ 1.2 versus 0.1 mmol/L; mean difference 1.1 mmol/L; 95% CI 0.4 to 1.9 mmol/L) and 2 hours (mean Δ 1.9 versus 0.3 mmol/L; mean difference 1.6 mmol/L; 95% CI 0.9 to 2.3 mmol/L). CONCLUSION Administration of a dextrose-containing bolus compared with normal saline did not lead to a lower rate of hospitalization for children with gastroenteritis and dehydration. There was, however, a greater reduction in serum ketone levels in patients who received 5% dextrose in normal saline solution.

Effects of Stem Cell Treatment in Human Patients With Peyronie Disease

CONTEXT Peyronie disease (PD) is a connective tissue disorder involving the formation of fibrous plaques in the tunica albuginea. Abnormal plaques and scar tissue create a chronic state of inflammation, causing increased curvature of the penis as well as erectile dysfunction. OBJECTIVE To determine the feasibility and effects of using placental matrix-derived mesenchymal stem cells (PM-MSCs) in the management of PD. METHODS In a prospective study, patients with PD were injected with PM-MSCs, and followed up at 6-week, 3-month, and 6-month intervals to assess changes in plaque volume, penile curvature, and erectile function status (measured using peak systolic velocity, end-diastolic velocity, and the International Index of Erectile Function questionnaire). RESULTS In the 5 patients enrolled in the study, statistically significant increases in peak systolic velocity occurred after PM-MSC injection (P<.01). Of a total of 10 plaques managed, 7 had disappeared completely at 3-month follow-up. Changes in end-diastolic velocity, stretched penile length, and penile girth were not statistically significant. CONCLUSION To our knowledge, this study is the first on the use of stem cells to manage PD in humans. The results suggest that PM-MSCs may be beneficial and effective as a nonsurgical treatment in patients with PD. Future studies with long-term follow-up in a larger sample of patients are warranted. (ClinicalTrials.gov number NCT02395029).