No abstract

The biallelic Interleukin-10 single nucleotide polymorphism (SNP) at -1082 of the promoter region linked to individual variation in cytokine inducibility has been strongly implicated in several pathological conditions including the development of, and outcomes in, septic shock during pneumococcal infection, acute respiratory distress syndrome, and cardiac dysfunction. However, the molecular basis of the SNP-mediated variable IL-10 production levels has not been explored. Here we report that the -1082G>A alleles in the promoter region of the human IL-10 gene physically interact with a nuclear protein in an allele-specific manner that results in different levels of IL-10 transcription. This protein has been identified as poly ADP-ribose polymerase 1 (PARP-1). We show that PARP-1 acts as a transcription repressor, and its DNA-binding activity is strongly regulated in macrophages that engulf apoptotic cells but not stimulated with lippopolysaccharides. These findings unveil a novel role of PARP-1 in the regulation of IL-10 production in an allele-dependent way, which determines individual susceptibility to sepsis-induced inflammatory pathology and the immunological sequelae in a physiological process where clearance of infection-induced apoptotic cells by professional phagocytes triggers the cytokine synthesis.

This study suggests that vacuum-assisted closure therapy can modulate nerve fiber and neuropeptide production in the wound. Optimized kinetics of vacuum-assisted closure application may provide an opportunity for clinicians to further improve wound healing in denervated wounds such as pressure sores and diabetic foot ulcerations.

Cytomegalovirus (CMV) viremia continues to cause significant morbidity and mortality in kidney transplant patients with clinical complications including organ rejection and death. Whole blood gene expression dynamics in CMV viremic patients from onset of DNAemia through convalescence has not been well studied to date in humans. To evaluate how CMV infection impacts whole blood leukocyte gene expression over time, we evaluated a matched cohort of 62 kidney transplant recipients with and without CMV DNAemia using blood samples collected at multiple time points during the 12-month period after transplant. While transcriptomic differences were minimal at baseline between DNAemic and non-DNAemic patients, hundreds of genes were differentially expressed at the long-term timepoint, including genes enriching for pathways important for macrophages, interferon, and IL-8 signaling. Amongst patients with CMV DNAemia, the greatest amount of transcriptomic change occurred between baseline and 1-week post-DNAemia, with increase in pathways for interferon signaling and cytotoxic T cell function. Time-course gene set analysis of these differentially expressed genes revealed that most of the enriched pathways had a significant time-trend. While many pathways that were significantly down- or upregulated at 1 week returned to baseline-like levels, we noted that several pathways important in adaptive and innate cell function remained upregulated at the long-term timepoint after resolution of CMV DNAemia. Differential expression analysis and time-course gene set analysis revealed the dynamics of genes and pathways involved in the immune response to CMV DNAemia in kidney transplant patients. Understanding transcriptional changes caused by CMV DNAemia may identify the mechanism behind patient vulnerability to CMV reactivation and increased risk of rejection in transplant recipients and suggest protective strategies to counter the negative immunologic impact of CMV. These findings provide a framework to identify immune correlates for risk assessment and guiding need for extending antiviral prophylaxis.

No abstract

Objectives: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19).

We report a case of a 17‐year‐old healthy male presenting with multisystem hyperinflammatory shock temporally associated with COVID‐19. Cardiac involvement was suspected based on evidence of significant cardiac injury (elevated cardiac biomarkers, electrocardiographic and echocardiographic abnormalities). Cardiac magnetic resonance imaging was performed demonstrating global biventricular systolic dysfunction, as well as a small area of T2 hyperintensity and mid‐wall late gadolinium enhancement. This case discusses the varied cardiac involvement in pediatric patients with COVID‐19 infection and highlights that cardiac injury is not just limited to hyperinflammatory syndrome related global dysfunction but a more focal myocarditis can also be seen.

OBJECTIVEPosterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) can be associated with significant blood loss. It has been suggested that blood loss is greater in different racial groups. The purpose of this study was to evaluate differences in blood loss between African American and Caucasian patients undergoing PSF for AIS.METHODSA retrospective review was performed of patients aged 10–18 years with AIS who were treated with PSF from 2014 to 2017 at a single children’s healthcare system. Patient demographic, radiographic, and operative data were obtained from medical records. Intraoperative blood loss was calculated using the formula described by Waters et al. Patients who declined reporting their race or had prior spinal surgery, neuromuscular or syndromic diagnoses, a history of cardiac or thoracic surgery, or a bleeding disorder were excluded. Blood loss variables were log-transformed for normality and modeled using multivariable linear regression.RESULTSA total of 433 PSFs for AIS qualified for the analysis. The average age was 14.1 years, and 73.7% of the patients were female. With respect to race, 44.6% identified themselves as African American. There was no significant difference in blood loss (p = 0.31) or blood loss per level fused (p = 0.36) in African American patients. African American patients, however, did have significantly lower preoperative hemoglobin and hematocrit levels and greater operating room time than Caucasian patients (p < 0.001). There was no difference between race and transfusion rate.CONCLUSIONSThere appears to be no relationship between race and blood loss during PSF for AIS. Standardized protocols for minimizing perioperative blood loss can be applied to both Caucasian and African American patients.