Clement D. Marshall

Relationship of Serum S100B Levels and Intracranial Injury in Children With Closed Head Trauma

OBJECTIVE: To determine if serum levels of S100B are higher in children with CHT and ICI as detected by cranial CT and if long bone fractures affect the level of S100B in children with CHT and skeletal injury. METHODS: Children <18 years of age who presented to an urban pediatric emergency department or were transferred from a referral hospital within 6 hours after accidental closed head trauma and who underwent cranial computed tomography were enrolled prospectively. Mean serum S100B levels for children with or without intracranial injury (ICI) and long-bone fractures were evaluated through analysis of covariance. RESULTS: One hundred fifty-two children, 24 with ICI and 128 without ICI, were enrolled prospectively. Twenty-five children had long-bone fractures. Children with ICI were significantly younger than those without ICI (6.9 vs 9.8 years; P = .01). The time of venipuncture after injury was significantly later in children with ICI (P = .03). Mean S100B levels were significantly greater for children with ICI (212.9 vs 84.4 ng/L; P = .001), children with long-bone fractures (P = .008), and nonwhite children (P = .03). After controlling for time of venipuncture, long-bone fractures, and race, mean S100B levels were still greater for children with ICI (409 vs 118 ng/L; P = .001). The ability of serum S100B measurements to detect ICI, determined as the area under the curve, was 0.67. CONCLUSIONS: After controlling for time of venipuncture, long-bone fractures, and race, S100B levels were still higher in children with ICI than in those without ICI. However, the ability of serum S100B measurements to detect ICI was poor.

Detection of hypoventilation by capnography and its association with hypoxia in children undergoing sedation with ketamine.

Objectives: Hypopneic hypoventilation, a decrease in tidal volume without a change in respiratory rate, is not easily detected by standard monitoring practices during sedation but can be detected by capnography. Our goal was to determine the frequency of hypopneic hypoventilation and its association with hypoxia in children undergoing sedation with ketamine. Methods: Children who received intravenous ketamine with or without midazolam for sedation in a pediatric emergency department were prospectively enrolled. Heart rate, respiratory rate, pulse oximetry, and end-tidal carbon dioxide (ETCO2) levels were recorded every 30 seconds. Results: Fifty-eight subjects were included in this study. Fifty percent of subjects had recorded ETCO2 values less than 30 mm Hg without a rise in respiratory rate. Twenty-eight percent of subjects experienced a decrease in pulse oximetry less than 95%. Patients who experienced a persistent decrease in ETCO2 at least 30 seconds in length were much more likely to have a persistent decrease in pulse oximetry than those with normal or transient decreases in ETCO2 (relative risk, 6.6; 95% confidence interval, 1.4-30.5). Decreases in ETcO2 occurred on an average of 3.7 minutes before decreases in pulse oximetry. Conclusions: Hypopneic hypoventilation as detected by capnography is common in children undergoing sedation with ketamine with or without midazolam. Hypoxia is frequently preceded by low ETCO2 levels. Further studies are needed to determine if the addition of routine monitoring with capnography can reduce the frequency of hypoxia in children undergoing sedation.

Mesenchymal Stromal Cells as Cell-Based Therapeutics for Wound Healing

Chronic wounds are a source of substantial morbidity for patients and are a major financial burden for the healthcare system. There are no current therapies that reliably improve nonhealing wounds or reverse pathological scarring. Mesenchymal stromal cells (MSCs) are a promising source of novel cell-based therapies due to the ease of their harvest and their integral role in the native wound repair process. Recent work has addressed the problems of loss of plasticity and off-target delivery through use of modern bioengineering techniques. Here we describe the applications of MSCs harvested from different sources to the wound healing process and recent advances in delivery of MSCs to targeted sites of injury.

A Comparison of Traditional versus Contemporary Immunosuppressive Regimens in Pediatric Heart Recipients

OBJECTIVES To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction). STUDY DESIGN We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups. RESULTS The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P < .001) or neutropenia (10% vs 0%, P = .019). However, more contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15). CONCLUSIONS A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival.

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

The monocyte lineage is essential to normal wound healing. Macrophage inhibition or knockout in mice results in impaired wound healing through reduced neovascularization, granulation tissue formation, and reepithelialization. Numerous studies have either depleted macrophages or reduced their activity in the context of wound healing. Here, we demonstrate that by increasing the number of macrophages or monocytes in the wound site above physiologic levels via pullulan-collagen composite dermal hydrogel scaffold delivery, the rate of wound healing can be significantly accelerated in both wild-type and diabetic mice, with no adverse effect on the quality of repair. Macrophages transplanted onto wounds differentiate into M1 and M2 phenotypes of different proportions at various time points, ultimately increasing angiogenesis. Given that monocytes can be readily isolated from peripheral blood without in vitro manipulation, these findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases.

Minimizing Skin Scarring through Biomaterial Design

Wound healing continues to be a major burden to patients, though research in the field has expanded significantly. Due to an aging population and increasing comorbid conditions, the cost of chronic wounds is expected to increase for patients and the U.S. healthcare system alike. With this knowledge, the number of engineered products to facilitate wound healing has also increased dramatically, with some already in clinical use. In this review, the major biomaterials used to facilitate skin wound healing will be examined, with particular attention allocated to the science behind their development. Experimental therapies will also be evaluated.

Stem cells and chronic wound healing: state of the art

Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based thera- peutics. Stem cells promise improved therapies for healing chronic wounds, but further studies

Scarless wound healing: Transitioning from fetal research to regenerative healing

Since the discovery of scarless fetal skin wound healing, research in the field has expanded significantly with the hopes of advancing the finding to adult human patients. There are several differences between fetal and adult skin that have been exploited to facilitate scarless healing in adults including growth factors, cytokines, and extracellular matrix substitutes. However, no one therapy, pathway, or cell subtype is sufficient to support scarless wound healing in adult skin. More recently, products that contain or mimic fetal and adult uninjured dermis were introduced to the wound healing market with promising clinical outcomes. Through our review of the major experimental targets of fetal wound healing, we hope to encourage research in areas that may have a significant clinical impact. Additionally, we will investigate therapies currently in clinical use and evaluate whether they represent a legitimate advance in regenerative medicine or a vulnerary agent. WIREs Dev Biol 2018, 7:e309. doi: 10.1002/wdev.309

Plug the Hole--A Bailout Option for Acute Focal Aortic Rupture.

BACKGROUND Focal aortic rupture may result from expanding aneurysms, penetrating aortic wall ulcerations, or virulent infections. An urgent repair of paravisceral focal aortic rupture is associated with high morbidity. A staged repair approach may provide an alternative option. CASE REPORT A 64-year-old woman presented with acute focal rupture of the posterior paravisceral aortic wall and was progressing to hemorrhagic shock and mesenteric ischemia. Given the patients dire condition, an endovascular approach was used to plug her focal aortic wall defect using a ventricular septal defect occluder device. Subsequently, the patient underwent resuscitation, stabilization, and operative exploration. Postoperatively, she recovered well from this staged approach. CONCLUSIONS This case provides an example of a staged endovascular plugging of an acute paravisceral focal aortic rupture. In select cases, this type of repair strategy is feasible, until off-the-shelf endovascular repair options become a reality.

Repair of Anomalous Left Coronary Artery From the Right Pulmonary Artery: A Series of Nine Cases.

Background: Repair of anomalous left coronary artery from the right pulmonary artery presents a particular technical challenge to the congenital cardiac surgeon. There is disagreement in the literature over the optimal technique for this defect, with some authors advocating for unroofing of the periaortic segment of coronary artery, while others prefer direct aortic reimplantation of the artery. Methods: We performed a retrospective study examining outcomes of patients who were repaired for this anomaly at our institution. In-hospital and outpatient follow-up data were analyzed. Results: Nine patients were identified. Most patients had poor left ventricular function at the time of surgery. All patients in our series were repaired using the direct coronary transfer technique. To date there were no mortalities among the study participants. At last follow-up, all patients with available echocardiograms had normal ventricular function. One patient required reoperation for anastomotic stenosis. Conclusions: We demonstrate that using the technique of direct coronary transfer to the aorta, we have achieved excellent results with repair of this defect.