Single-Use Negative Pressure Wound Therapy Applied on Various Wound Types: An Interventional Case Series.

PURPOSE: The purpose of this study was to determine whether a single-use negative pressure wound therapy (NPWT) system achieves individualized goals of therapy when used to treat patients with a variety of wound types. DESIGN: Multiple case series. SUBJECTS AND SETTING: The same comprised 25 participants; their mean age was 51.2 years (SD: 18.2; range: 19-79 years); 14 were male (56%) and 11 were female (44%). Seven study participants withdrew from study participation. Wound etiologies vary; 4 had diabetic foot ulcers; 1 had a full-thickness pressure injury; 7 were treated for management of an abscess or cyst; 4 had necrotizing fasciitis, 5 had nonhealing postsurgical wounds, and 4 had wounds of other etiologies. Data were collected at 2 ambulatory wound care clinics located in the Southeastern United States (Augusta and Austell, Georgia). METHODS: A single-outcome measure was selected for each participant by his or her attending physician at a baseline visit. Selected end points were (1) decrease in wound volume, (2) decrease in size of the tunneling area, (3) decrease in size of the undermining, (4) decrease in the amount of slough, (5) increase in granulation tissue formation, (6) decrease in periwound swelling, and (7) wound bed progression toward transition to another treatment modality (such as standard dressing, surgical closure, flap, or graft). Progress toward the individualized goal was monitored until the goal was achieved (study end point) or a maximum of 4 weeks following initiation of treatment. RESULTS: The most common primary treatment goal was to achieve a decrease in wound volume (22 of 25 study participants), and the goal to increase granulation tissue was chosen for the remaining 3 study participants. A majority of participants (18 of 23, 78.3%) reached their individualized treatment outcome. The remaining 5 participants (21.7%) were withdrawn during the study (for reasons not related to the therapy). The median (interquartile range [IQR]) duration of NPWT therapy was 19 days (IQR: 14-21 days). Between baseline and the final assessment, median reductions in wound area and volume were 42.7% (IQR: 25.7-71.5) and 87.5% (IQR: 30.7-94.6). CONCLUSIONS: The single-use NPWT system achieved multiple individualized treatment objectives in a variety of wound types. Individually selected goals of therapy were met by all study participants who completed the study.

Hemopexin in severe inflammation and infection: mouse models and human diseases.

INTRODUCTION: Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients. METHODS: We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants. RESULTS: Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations. CONCLUSIONS: Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration.

Benchmarking outcomes in the critically injured burn patient.

OBJECTIVE: To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers. BACKGROUND: Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries. METHODS: We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care. RESULTS: Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 ± 18.3 for adults and 57.8 ± 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant. CONCLUSIONS: This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions.

Resolvin D2 restores neutrophil directionality and improves survival after burns.

Following severe burns and trauma injuries, the changes of neutrophil migratory phenotype are a double-edged sword. Activated neutrophils migrate into injured tissues and help contain microbial infections, but they can also enter normal tissues and damage vital organs. Depleting the neutrophils from circulation protects vital organs against neutrophil-induced damage but leaves the body exposed to infectious complications. Here we show that restoring normal neutrophil migratory phenotype in rats with burn injuries correlates with improved survival in a classical double-injury model of sequential burn and septic insults. We uncovered that the directionality of neutrophils from burned rats can be restored both in vitro by 1 nM resolvin D2 (RvD2) and in vivo by RvD2 for 7 d, 25 ng/kg body mass (8-10 ng/rat). Restoring neutrophil directionality dramatically increases survival after a second septic insult at d 9 postburn. Survival of RvD2-treated animals increases from 0 to 100% after lipopolysaccharide injection and is extended by 1 wk after cecal ligation. Survival does not significantly increase when the restoration of neutrophil directionality is incomplete, following shorter regimens of RvD2. We conclude that restoring neutrophil directionality using RvD2 could have prophylactic value and delay lethal complications after burn injuries.

Neurochemical heterogeneity of rats predicted by different measures to be high ethanol consumers.

BACKGROUND: Alcoholism is a heterogeneous disease, with subjects possibly differing both in the best measure that predicts their excess consumption and in their most effective pharmacotherapy. Two different measures, high novelty-induced activity and high-fat-induced triglycerides (TGs), are known to identify subgroups of animals prone to consuming higher amounts of ethanol (EtOH). The question investigated here is whether these subgroups are, in fact, similar in their neurochemical phenotype that may contribute to their overconsumption. METHODS: EtOH-naïve, Sprague-Dawley rats were subgrouped based on the 2 predictor measures of activity or TG levels, and then quantitative real-time polymerase chain reaction and digoxigenin-labeled in situ hybridization were used to measure their expression of hypothalamic peptides that affect EtOH intake. In additional subgroups subsequently trained to drink 9% EtOH, the opioid antagonist and alcoholism medication, naltrexone, was tested at a low dose (0.02 mg/kg, s.c.) to determine the rats' sensitivity to its effects. RESULTS: The 2 measures, while both effective in predicting amount of EtOH intake, were found to identify distinctive subgroups. Rats with high compared to low activity exhibited significantly greater expression of galanin and enkephalin in the paraventricular nucleus (PVN) and of orexin in the perifornical lateral hypothalamus (PFLH), but no difference in melanin-concentrating hormone in PFLH or neuropeptide Y in arcuate nucleus. This contrasts with rats having high TG, which exhibited greater expression only of PVN galanin, along with reduced PFLH orexin. The high-activity rats with elevated enkephalin, but not high-TG rats, were also unusually sensitive to naltrexone, which significantly reduced their alcohol intake. CONCLUSIONS: In addition to revealing differences in endogenous peptides and drug responsiveness in predicted high EtOH drinkers, this study demonstrates that these disturbances differ markedly between the 2 at-risk subgroups. This indicates that simple tests may be effective in identifying subjects most responsive to a specific pharmacotherapy.

Glucose metabolism during the early "flow phase" after burn injury.

BACKGROUND: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions. MATERIALS AND METHODS: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn. An EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion 3 d after treatment. PET imaging of the hind limbs was conducted to determine the rates of peripheral O(2) and glucose utilization. Each animal also received a primed constant infusion of [6,6-(2)H(2)] glucose to determine endogenous glucose production. RESULTS: The fasting blood glucose in the burned rabbits was higher than that in the sham group. Under EIC conditions, the sham burn group required more exogenous dextrose than the B group to maintain blood glucose at physiological levels (22.2 ± 2.6 versus 13.3 ± 2.9 mg/min, P < 0.05), indicating a state of IR. PET imaging demonstrated that the rates of O(2) consumption and (18)F 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the B group. CONCLUSIONS: These findings demonstrated that hyperglycemia and IR develop during the early "flow phase" after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia at this stage.

The safety and efficacy of parenteral nutrition among pediatric patients with burn injuries.

OBJECTIVE: Although enteral nutrition is the ideal mode of nutritional support following burn injury, it is often interrupted during episodes of severe sepsis and hemodynamic instability, leading to significant energy and protein deficits. Parenteral nutrition is not commonly used in burn centers due to concerns that it will lead to hyperglycemia, infection, and increased mortality. However, parenteral nutrition is often utilized in our burn unit when goal rate enteral nutrition is not feasible.To determine the safety and efficacy of a standardized protein-sparing parenteral nutrition protocol in which glucose infusion is limited to 5-7 mg/kg/hour. DESIGN: Retrospective observational study. SETTING: Pediatric burn hospital. PATIENTS: A retrospective medical record review of all children admitted to our hospital with burns ≥ 30% total body surface area was conducted. Only patients admitted within one week of injury and who survived > 24 hours after admission were included in this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 105 patients who met the inclusion criteria, 96 (91%) received parenteral nutrition or a combination of parenteral nutrition and enteral nutrition at some point during their care. Nine patients received only enteral nutrition. Demographic data were similar between groups. Protein intake was significantly higher in the parenteral nutrition group. Incidence of catheter-related blood infections did not differ between groups. Use of parenteral nutrition was not associated with blood or respiratory infections. Overall mortality rate was low (4%), as most patients (96%) achieved wound closure and were discharged home. CONCLUSIONS: Judicious use of parenteral nutrition is a safe and effective means of nutritional support when goal enteral nutrition cannot be achieved. A hypocaloric, high-nitrogen parenteral nutrition solution can reduce energy and protein deficits while minimizing complications commonly associated with parenteral nutrition usage.

Analysis of factorial time-course microarrays with application to a clinical study of burn injury.

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

Application and Management of Cultured Epidermal Autografts on Posterior Burns-A 5-Year, Multicenter, Retrospective Review of Outcomes.

Severe burns on the posterior trunk present a treatment challenge in that these surfaces bear the major portion of body weight, with shearing forces exerted when changing the patient from supine to prone position. In their high-volume center at Burn and Reconstructive Centers of America, the authors developed protocols for use of cultured epidermal autografts (CEAs) for coverage of large burns, including those specific to posterior burns. This paper describes techniques and approaches, including milestone timelines, to treat and manage these patients. Key factors for successful treatment begin with early development of a detailed surgical plan. Members of the trained team participate in the plan and understand standard procedures and any deviation. Patients are identified early for treatment with CEA so that a full thickness skin biopsy can be sent to the manufacturer for processing. Patients with >30% total body surface area (TBSA) burns are considered for CEA burn wound coverage due to the potential for conversion of superficial partial thickness to deep partial thickness or full thickness burns over hospitalization time. We also present the outcomes in patients with posterior trunk burns treated with CEA from 2016 to 2019 in three participating centers within our network. Data in 40 patients with mean TBSA of 56% demonstrated a high rate of successful CEA engraftment (83%), and overall survival rate (90%) following one or two applications with CEA and/or CEA + split thickness skin graft (STSG). Development of standard treatment protocols and surgical plans has enabled positive outcomes with CEA in severe burns including posterior burns.

The role of personal-use negative pressure wound therapy with enhanced functionality in achieving wound-related treatment goals: a small prospective study.

BACKGROUND: NPWT is widely used to manage hard-to-heal wounds, and many different devices are available. Personal-use NPWT systems are becoming more popular, although current options have limited functionality. PURPOSE: The primary objective was to determine acceptable progress of wounds towards a predefined goal of therapy for a variety of open wounds being treated with a novel NPWT personal-use system with enhanced functionality. METHODS: In this prospective, nonrandomized, interventional study, patients were treated with a personal-use NPWT system over 4 weeks, initially in a wound care clinic setting, and were discharged home with the device. Clinician satisfaction with the device was also evaluated. RESULTS: Ten patients were evaluated. Acceptable progress towards all predetermined goals was reached for all patients; a median reduction in wound volume of 84.6% and improved granulation was achieved within the 4-week treatment period. No device-related deficiencies were reported. In general, clinicians were satisfied with the device's ease of use and mobility. CONCLUSION: Personal-use NPWT is easy to use, has positive effects on healing on a variety of wound types, and is well accepted by clinicians.

Developmental changes in embryonic hypothalamic neurons during prenatal fat exposure.

Maternal consumption of a fat-rich diet during pregnancy, which causes later overeating and weight gain in offspring, has been shown to stimulate neurogenesis and increase hypothalamic expression of orexigenic neuropeptides in these postnatal offspring. The studies here, using an in vitro model that mimics in vivo characteristics after prenatal high-fat diet (HFD) exposure, investigate whether these same peptide changes occur in embryos and if they are specific to neurons. Isolated hypothalamic neurons were compared with whole hypothalamus from embryonic day 19 (E19) embryos that were prenatally exposed to HFD and were both found to show similar increases in mRNA expression of enkephalin (ENK) and neuropeptide Y (NPY) compared with that of chow-exposed embryos, with no change in melanin-concentrating hormone, orexin, or galanin. Further examination using immunofluorescence cytochemistry revealed an increase in the number of cells expressing ENK and NPY. By plotting the fluorescence intensity of each cell as a probability density function, three different populations of neurons with low, medium, or high levels of ENK or NPY were found in both HFD and chow groups. The prenatal HFD shifted the density of neurons from the population containing low peptide levels to the population containing high peptide levels. This study indicates that neuronal culture is a useful in vitro system for studying diet effects on neuronal development and shows that prenatal HFD exposure alters the population of hypothalamic neurons containing ENK and NPY in the embryo. These changes may contribute to the increase in HFD intake and body weight observed in offspring.

Transpulmonary thermodilution for hemodynamic measurements in severely burned children.

INTRODUCTION: Monitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients. METHODS: This prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra- and intergroup comparisons. RESULTS: Seventy-nine patients with a mean age (±SD) of 9 ± 5 years and a mean TBSA burn (±SD) of 64% ± 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury. CONCLUSIONS: Continuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay.

Somatic Marker Production Deficits do not Explain the Relationship between Psychopathic Traits and Utilitarian Moral Decision Making.

In moral dilemma tasks, high levels of psychopathic traits often predict increased utilitarian responding-specifically, endorsing sacrificing one person to save many. Research suggests that increased arousal (i.e., somatic marker production) underlies lower rates of utilitarian responding during moral dilemmas. Though deficient somatic marker production is characteristic of psychopathy, how this deficit affects the psychopathy-utilitarian connection remains unknown. We assessed psychopathic traits in undergraduates, as well as behavioral performance and skin conductance level reactivity (SCL-R; a measure of somatic marker production) during a moral dilemma task. High psychopathic traits and low SCL-R were associated with increased utilitarian decisions in dilemmas involving direct personal harm. Psychopathic traits were unrelated to SCL-R, nor did SCL-R mediate the relationship between psychopathy and utilitarianism. The present study did not find evidence that somatic marker production explains the connection between utilitarianism and psychopathy in a college population. Further research is necessary to identify the neural mechanisms relating psychopathy and moral decision-making in nonclinical samples.

Prospective, Single-center, Open-label, Pilot Study Using Cryopreserved Umbilical Tissue Containing Viable Cells in the Treatment of Complex Acute and Chronic Wounds.

INTRODUCTION: Complex wounds with exposed bone, muscle, tendon, or hardware continue to be a therapeutic challenge for wound care providers. Wounds with exposed structures are more susceptible to infection, necrosis, and amputation. As such, rapid granulation to cover exposed deep tissue structures is essential for patient recovery. OBJECTIVE: In this prospective, pilot study, the authors evaluate the clinical outcomes of a cryopreserved umbilical tissue graft containing viable cells (vCUT) in the treatment of complex wounds. MATERIALS AND METHODS: Ten patients with 12 wounds each received 1 application of vCUT. Two patients did not complete the study and were removed from the per-protocol population. Data analyses were performed on the remaining 8 patients with 10 wounds. The average wound area was 16.5 cm2 with an average duration of 10 months. Post-application, patients were followed for an additional 4 weeks for granulation, closure, and safety outcomes. RESULTS: By the end of the study, 8 of 10 (80.0%) vCUT-treated wounds achieved 100% granulation, and 3 wounds (30.0%) went on to achieve complete closure. The median area reduction was 40.5% and the median volume reduction was 59.4%. CONCLUSIONS: The results of this study suggest vCUT in conjunction with standard of care can be a viable treatment option for acute and chronic lower extremity complex wounds.

The Impact of Callous-Unemotional Traits and Externalizing Tendencies on Neural Responsivity to Reward and Punishment in Healthy Adolescents.

Both externalizing behavior and callous-unemotional (CU) traits in youth are precursors to later criminal offending in adulthood. It is posited that disruptions in reward and punishment processes may engender problematic behavior, such that CU traits and externalizing behavior may be linked to a dominant reward response style (e.g., heightened responsivity to rewards) and deficient punishment-processing. However, prior research has generated mixed findings and work examining both the sole and joint contribution of CU traits and externalizing problems related to functional brain alterations is lacking. In this pilot functional magnetic resonance imaging study, we measured externalizing behavior and CU traits in a community sample of adolescents (n = 29) and examined their impacts on brain activity associated with anticipation and receipt of reward and punishment using the Modified Monetary Incentive Delay task. We found that CU traits were associated with greater activation of the ventral striatum (VST) during reward anticipation. However, this effect became non-significant after controlling for externalizing behavior, indicating substantial overlap between the CU and externalizing measures in explaining VST activation when anticipating reward. In addition, externalizing behavior (but not CU) was significantly negatively associated with amygdala activation during punishment receipt, even after controlling for CU traits. The present findings extend previous evidence of hyper-responsivity to reward and hypo-responsivity to punishment in relation to psychopathic traits and antisocial behavior to non-clinical, non-incarcerated youths.

Respiratory Sinus Arrhythmia Activity Predicts Internalizing and Externalizing Behaviors in Non-referred Boys.

Atypical respiratory sinus arrhythmia (RSA), a biomarker of emotion dysregulation, is associated with both externalizing and internalizing behaviors. In addition, social adversity and gender may moderate this association. In this study, we investigated if RSA (both resting RSA and RSA reactivity in an emotion regulation task) predicts externalizing and/or internalizing behaviors and the extent to which social adversity moderates this relationship. Two hundred and fifty-three children (at Time 1, mean age = 9.05, SD = 0.60, 48% boys) and their caregivers from the community participated in this study. Resting RSA and RSA reactivity were assessed, and caregivers reported children's externalizing and internalizing behaviors at both Time 1 and Time 2 (1 year later). We found that lower resting RSA (but not RSA reactivity) at Time 1 was associated with increased externalizing and internalizing behaviors at Time 2 in boys, even after controlling for the effects of Time 1 behavioral problems and Time 2 age. Moreover, there was a significant interaction effect between Time 1 resting RSA and social adversity such that lower resting RSA predicted higher externalizing and internalizing behaviors in boys only under conditions of high social adversity. Follow-up analyses revealed that these predictive effects were stronger for externalizing behavior than for internalizing behavior. No significant effects were found for girls. Our findings provide further evidence that low resting RSA may be a transdiagnostic biomarker of emotion dysregulation and a predisposing risk factor for both types of behavior problems, in particular for boys who grow up in adverse environments. We conclude that biosocial interaction effects and gender differences should be considered when examining the etiological mechanisms of child psychopathology.

Social Adversity and Antisocial Behavior: Mediating Effects of Autonomic Nervous System Activity.

The display of antisocial behaviors in children and adolescents has been of interest to criminologists and developmental psychologists for years. Exposure to social adversity is a well-documented predictor of antisocial behavior. Additionally, measures of autonomic nervous system (ANS) activity, including heart rate variability (HRV), pre-ejection period (PEP), and heart rate, have been associated with antisocial behaviors including rule-breaking and aggression. Social neuroscience research has begun to investigate how neurobiological underpinnings affect the relationship between social adversity and antisocial/psychopathic behavior in children and adolescents. This study investigated the potential mediating effects of ANS activity on the relationship between social adversity and antisocial behavior in a group of 7- to 10-year-old children from the community (N = 339; 48.2% male). Moderated multiple mediation analyses revealed that low resting heart rate, but not PEP or HRV, mediated the relationship between social adversity and antisocial behavior in males only. Social adversity but not ANS measures were associated with antisocial behavior in females. Findings have implications for understanding the neural influences that underlie antisocial behavior, illustrate the importance of the social environment regarding the expression of these behaviors, and highlight essential gender differences.