Omar Nunez Lopez

Special considerations of age: The pediatric burned patient

Abstract Children are disproportionately affected by burn injuries. Differences between adult and pediatric burns range from epidemiological characteristics to pathophysiological considerations, which vary between different age subgroups. All these factors must be taken into account in each phase of burn care. This chapter reviews the most important aspects of the management of the pediatric burned patient.

STAT3 inhibition suppresses hepatic stellate cell fibrogenesis: HJC0123, a potential therapeutic agent for liver fibrosis

Hepatic Stellate Cells (HSCs) are the major source of the excessive extracellular matrix (ECM) production that replaces liver parenchyma with fibrous tissue during liver fibrosis. The signal transducer and activator of transcription 3 (STAT3) promotes HCSs survival, proliferation, and activation contributing to fibrogenesis. We have previously used a fragment-based drug design approach and have discovered a novel STAT3 inhibitor, HJC0123. Here, we explored the biological effects of HJC0123 on the fibrogenic properties of HSCs. HJC0123 treatment resulted in the inhibition of HSCs proliferation at submicromolar concentrations. HJC0123 reduced the phosphorylation, nuclear translocation, and transcriptional activity of STAT3. It decreased the expression of STAT3-regulated proteins, induced cell cycle arrest, promoted apoptosis and downregulated SOCS3. HJC0123 treatment inhibited HSCs activation and downregulated ECM protein fibronectin and type I collagen expression. In addition, HJC0123 increased IL-6 production and decreased TGF-β induced Smad2/3 phosphorylation. These results demonstrate that HJC0123 represents a novel STAT3 inhibitor that suppresses the fibrogenic properties of HSCs, suggesting its therapeutic potential in liver fibrosis.

Predicting and managing sepsis in burn patients: Current perspectives

Modern burn care has led to unprecedented survival rates in burn patients whose injuries were fatal a few decades ago. Along with improved survival, new challenges have emerged in the management of burn patients. Infections top the list of the most common complication after burns, and sepsis is the leading cause of death in both adult and pediatric burn patients. The diagnosis and management of sepsis in burns is complex as a tremendous hypermetabolic response secondary to burn injury can be superimposed on systemic infection, leading to organ dysfunction. The management of a septic burn patient represents a challenging scenario that is commonly encountered by providers caring for burn patients despite preventive efforts. Here, we discuss the current perspectives in the diagnosis and treatment of sepsis and septic shock in burn patients.

Race and outcomes in gastroschisis repair: a nationwide analysis☆☆☆★★★☆☆☆

BACKGROUND The incidence of gastroschisis has increased 30% between the periods 1995-2005 and 2006-2012, with the largest increase in Black neonates born to Black mothers younger than 20years old. OBJECTIVE Racial disparities in peri- and post-operative outcomes have been previously identified in several types of adult and pediatric surgical patients. Is there an association between race and clinical outcomes and healthcare resource utilization in neonates with gastroschisis? METHODS Retrospective study using national administrative data from the Kids Inpatient Database (KID) from 2006, 2009, and 2012 for neonates (age<28days) with gastroschisis. Multivariable logistic regression was constructed to determine the association of race and socioeconomic characteristics with complications and mortality; linear regression was used for length of stay and hospital charges. RESULTS We identified 3846 neonates with gastroschisis that underwent surgical repair, including 676 patients with complex gastroschisis. When controlling for birth weight, payer status, socioeconomic status, and hospital characteristics, Black neonates had increased odds of having complex gastroschisis and associated atresias. Mortality was higher in patients with complex gastroschisis, patients from the lowest income quartiles, and patients with Medicaid as primary payer (compared to those with private insurance). Length of stay (LOS) was increased in patients with complex gastroschisis, birth weight <2500g, and Medicaid patients. Hospital charges were higher in complex gastroschisis, Black and Hispanic neonates (as compared to Whites), males, birth weight <2500g, and Medicaid patients. CONCLUSIONS There is an association between race and complex gastroschisis, associated intestinal atresias, and total charges in neonates with gastroschisis. In addition, income status is associated with mortality and hospital charges while payer status is associated with complications, mortality, LOS, and hospital charges. Public health and prenatal interventions should target at-risk populations to improve clinical outcomes. PROGNOSIS STUDY Level of Evidence: II.

Mitochondrial bioenergetics in the metabolic myopathy accompanying peripheral artery disease

Peripheral artery disease (PAD) is a serious but relatively underdiagnosed and undertreated clinical condition associated with a marked reduction in functional capacity and a heightened risk of morbidity and mortality. The pathophysiology of lower extremity PAD is complex, and extends beyond the atherosclerotic arterial occlusion and subsequent mismatch between oxygen demand and delivery to skeletal muscle mitochondria. In this review, we evaluate and summarize the available evidence implicating mitochondria in the metabolic myopathy that accompanies PAD. Following a short discussion of the available in vivo and in vitro methodologies to quantitate indices of muscle mitochondrial function, we review the current evidence implicating skeletal muscle mitochondrial dysfunction in the pathophysiology of PAD myopathy, while attempting to highlight questions that remain unanswered. Given the rising prevalence of PAD, the detriment in quality of life for patients, and the associated significant healthcare resource utilization, new alternate therapies that ameliorate lower limb symptoms and the functional impairment associated with PAD are needed. A clear understanding of the role of mitochondria in the pathophysiology of PAD may contribute to the development of novel therapeutic interventions.

Surgical Management of Complications of Burn Injury

Abstract Various surgical complications can occur in burn patients resulting from pathologic progression of the burn injury itself or from iatrogenic etiologies. Burn patients are at risk for potential surgical complications involving multiple organ systems. Complications requiring operative management in the setting of a burn injury are relatively common and can compound an already overwhelming physiological response. These complications are often unavoidable, and clinicians must be thorough in the evaluation of patients with a significant burn injury. This chapter reviews the frequently encountered nonthermal surgical complications in burn patients with respect to diagnosis and management.

Cardiorespiratory Capacity and Strength Remain Attenuated in Children with Severe Burn Injuries at Over 3 Years Postburn

Objectives To compare physical capacity and body composition between children with burn injuries at approximately 4 years postburn and healthy, fit children. Study design In this retrospective, case‐control study, we analyzed the strength, aerobic capacity, and body composition of children with severe burn injuries (n = 40) at discharge, after completion of a 6‐ to 12‐week rehabilitative exercise training program, and at 3‐4 years postburn. Values were expressed as a relative percentage of those in age‐ and sex‐matched children for comparison (n = 40 for discharge and postexercise; n = 40 for 3.5 years postburn). Results At discharge, lean body mass was 89% of that in children without burn injuries, and exercise rehabilitation restored this to 94% (P < .01). At 3.5 years postburn, lean body mass (94%), bone mineral content (89%), and bone mineral density (93%; each P ≤ .02) remained reduced, whereas total body fat was increased (148%, P = .01). Cardiorespiratory fitness remained lower in children with burn injuries both after exercise training (75%; P < .0001) and 3.5 years later (87%; P < .001). Peak torque (60%; P < .0001) and average power output (58%; P < .0001) were lower after discharge. Although exercise training improved these, they failed to reach levels achieved in healthy children without burns (83‐84%; P < .0001) but were maintained at 85% and 82%, respectively, 3.5 years later (P < .0001). Conclusions Although the benefits of rehabilitative exercise training on strength and cardiorespiratory capacity are maintained at almost 4 years postburn, they are not restored fully to the levels of healthy children. Although the underlying mechanism of this phenomenon remains elusive, these findings suggest that future development of continuous exercise rehabilitation interventions after discharge may further narrow the gap in relation to healthy adolescents.

Herpesviradae infections in severely burned children

OBJECTIVE Burn-related immunosuppression can promote human herpesviridae infections. However, the effect of these infections on morbidity and mortality after pediatric burn injuries is unclear. METHODS We retrospectively analyzed pediatric patients with burns ≥10% of the total body surface area (TBSA) who were admitted between 2010 and 2015. On clinical suspicion of a viral infection, antiviral therapy was initiated. Viral infection was confirmed via Tzanck smear, viral culture, and/or PCR. Study endpoints were mortality, days of antiviral agent administration, type of viral test used, type of viral infection, and length of hospitalization. RESULTS Of the 613 patients were analyzed, 28 presented with clinically diagnosed viral infections. The use of Tzanck smears decreased over the past 5 years, whereas PCR and viral cultures have become standard. Patients with viral infections had significantly larger burns (53±15% vs. 38±18%, p<0.001); however, length of stay per TBSA burn was comparable (0.5±0.4 vs. 0.6±0.2, p=0.211). The most commonly detected herpesviridae was herpes simplex virus 1. Two patients died due to sepsis, which was accompanied by HSV infection. The mortality rate among all patients (2.7%) was comparable to that in the infected group (7.1%, p=0.898). Acyclovir was given systemically for 9±8days (N=76) and/or topically for 9±9days for HSV (N=39, combination of both N=33). Ganciclovir was prescribed in three cases for CMV. CONCLUSIONS Viral infections occur more commonly in patients suffering from larger burns, and HSV infections can contribute to mortality.

Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway

Hepatic stellate cell (HSC) activation is responsible for hepatic fibrogenesis and is associated with an overexpression of transcription 3 (STAT3). Luteolin, a common dietary flavonoid with potent anti-inflammatory properties, has previously demonstrated antifibrogenic properties in HSCs but the mechanism has not been fully elucidated. Activated human and rat hepatic stellate cell lines LX-2 and HSC-T6 were used to study the effects of luteolin on HSCs. Cellular proteins were determined by western blot and immunofluorescence. Cell proliferation was assessed with Alamar Blue assay. Luteolin significantly decreased LX-2 and HSC-T6 cell viability in a time-and-dose-dependent manner, as well as decreased HSC end-products α-smooth muscle actin (α-SMA), collagen I, and fibronectin. Luteolin decreased levels of total and phosphorylated STAT3, suppressed STAT3 nuclear translocation and transcriptional activity, and attenuated expression of STAT3-regulated proteins c-myc and cyclin D1. STAT3 specific inhibitors stattic and SH-4-54 demonstrated similar effects on HSC viability and α-SMA production. In LX-2 and HSC-T6 cells, luteolin demonstrates a potent ability to inhibit hepatic fibrogenesis via suppression of the STAT3 pathway. These results further elucidate the mechanism of luteolin as well as the effect of the STAT3 pathway on HSC activation.

Sociodemographic determinants of non-accidental traumatic injuries in children

BACKGROUND Traumatic injuries account for 18% of child abuse cases and 1680 children die from abuse annually. We set out to determine the impact of sociodemographic characteristics on resource utilization and outcomes in nonaccidental trauma (NAT). METHODS We used the Kids Inpatient Database to identify children with two main subgroups of child abuse diagnoses: NAT and other forms of child abuse. Income was represented by quartiles. Statistical analysis included descriptive statistics and regression analyses. RESULTS We identified 5617 children requiring hospital admission due to NAT. Medicaid insurance payer status was associated with higher rates of traumatic injuries than private insurance. Black race, male sex, and high-income-quartile were independent factors associated with increased cost. We identified an increased risk of mortality in younger children and those with self-pay/uninsured status. CONCLUSION NAT represents a prevalent cause of childhood mortality. This study identifies sociodemographic factors associated with increased occurrence, higher resource utilization, and increased mortality in NAT.