Deep and Superficial Debridement Techniques in Lower Extremity Split-thickness Skin Grafting.

Background: Patients with nonhealing lower extremity (LE) wounds often require a split-thickness skin graft (STSG) for closure. Nonviable tissue must be debrided before STSG inset. Our study aimed to compare differences in debridement depth on STSG outcomes. Methods: Chronic, atraumatic LE wounds receiving STSG from December 2014 to December 2022 at a single institution were reviewed. Demographics, wound characteristics, operative details, and outcomes were collected. Superficially debrided wounds were compared with wounds receiving deep debridement (DD), defined by debriding to the level of white tissue underlying the granulation tissue. Subanalysis was performed on wounds that had a negative and positive postdebridement culture. Primary outcome was graft failure. Results: Overall, 244 wounds in 168 patients were identified. In total, 158 (64.8%) wounds were superficially debrided and 86 (35.3%) received DD. The cohort had a median Charlson Comorbidity Index of 4 [interquartile range (IQR): 3]. Diabetes (56.6%) and peripheral artery disease (36.9%) were prevalent. The only statically significant demographic difference between groups was congestive heart failure (SD: 14.9% versus DD: 3.0%, P = 0.017). Wound size, depth, and all microbiology results were similar between groups. Postoperatively, the DD group demonstrated significantly less graft failure (10.5% versus 22.2%, P = 0.023). In a multivariate regression, DD was independently associated with lower odds of graft failure (OR: 0.0; CI, 0.0-0.8; P = 0.034). Sub-analysis of graft failure supported this finding in culture-positive wounds (DD: 7.6% versus DD: 22.1%, P = 0.018) but not in culture-negative wounds (13.6% versus 22.2%, P = 0.507). Conclusions: The DD technique demonstrates improved outcomes in chronic, culture-positive LE wounds receiving STSG.

Victims of human trafficking and exploitation in the healthcare system: a retrospective study using a large multi-state dataset and ICD-10 codes.

Trafficking and exploitation for sex or labor affects millions of persons worldwide. To improve healthcare for these patients, in late 2018 new ICD-10 medical diagnosis codes were implemented in the US. These 13 codes include diagnosis of adult and child sexual exploitation, adult and child labor exploitation, and history of exploitation. Here we report on a database search of a large US health insurer that contained approximately 47.1 million patients and 0.9 million provider organizations, not limited to large medical systems. We reported on any diagnosis with the new codes between 2018-09-01 and 2022-09-01. The dataset was found to contain 5,262 instances of the ICD-10 codes. Regression analysis of the codes found a 5.8% increase in the uptake of these codes per year, representing a decline relative to 6.7% annual increase in the data. The codes were used by 1,810 different providers (0.19% of total) for 2,793 patients. Of the patients, 1,248 were recently trafficked, while the remainder had a personal history of exploitation. Of the recent cases, 86% experienced sexual exploitation, 14% labor exploitation and 0.8% both types. These patients were predominantly female (83%) with a median age of 20 (interquartile range: 15-35). The patients were characterized by persistently high prevalence of mental health conditions (including anxiety: 21%, post-traumatic stress disorder: 20%, major depression: 18%), sexually-transmitted infections, and high utilization of the emergency department (ED). The patients' first report of trafficking occurred most often outside of a hospital or emergency setting (55%), primarily during office and psychiatric visits.

Epidermal growth factor treatment of female mice that express APOE4 at an age of advanced pathology mitigates behavioral and cerebrovascular dysfunction.

APOE4 is a major genetic risk factor for Alzheimer's disease and high amyloid-ß (Aß) levels in the brain are a pathological hallmark of the disease. However, the contribution of specific APOE-modulated Aß-dependent and Aß-independent functions to cognitive decline remain unclear. Increasing evidence supports a role of APOE in modulating cerebrovascular function, however whether ameliorating this dysfunction can improve behavioral function is still under debate. We have previously demonstrated that systemic epidermal growth factor (EGF) treatment, which is important for vascular function, at early stages of pathology (treatment from 6 to 8 months) is beneficial for recognition and spatial memory and cerebrovascular function in female mice that express APOE4. These data raise the important question of whether EGF can improve APOE4-associated cerebrovascular and behavioral dysfunction when treatment is initiated at an age of advanced pathology. Positive findings would support the development of therapies that target cerebrovascular dysfunction associated with APOE4 in aging and AD in individuals with advanced cognitive impairment. Therefore, in this study female mice that express APOE4 in the absence (E4FAD- mice) or presence (E4FAD+ mice) of Aß overproduction were treated from 8 to 10 months of age systemically with EGF. EGF treatment mitigated behavioral dysfunction in recognition memory and spatial learning and improved hippocampal neuronal function in both E4FAD+ and E4FAD- mice, suggesting that EGF treatment improves Aß-independent APOE4-associated deficits. The beneficial effects of EGF treatment on behavior occurred in tandem with improved markers of cerebrovascular function, including lower levels of fibrinogen, lower permeability when assessed by MRI and higher percent area coverage of laminin and CD31 in the hippocampus. These data suggest a mechanistic link among EGF signaling, cerebrovascular function and APOE4-associated behavioral deficits in mice with advanced AD-relevant pathology.

Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model.

Protein palmitoylation and depalmitoylation alter protein function. This post-translational modification is critical for synaptic transmission and plasticity. Mutation of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) causes infantile neuronal ceroid lipofuscinosis (CLN1), a pediatric neurodegenerative disease. However, the role of protein depalmitoylation in synaptic maturation is unknown. Therefore, we studied synapse development in Ppt1-/- mouse visual cortex. We demonstrate that the developmental N-methyl-D-aspartate receptor (NMDAR) subunit switch from GluN2B to GluN2A is stagnated in Ppt1-/- mice. Correspondingly, Ppt1-/- neurons exhibit immature evoked NMDAR currents and dendritic spine morphology in vivo. Further, dissociated Ppt1-/- cultured neurons show extrasynaptic, diffuse calcium influxes and enhanced vulnerability to NMDA-induced excitotoxicity, reflecting the predominance of GluN2B-containing receptors. Remarkably, Ppt1-/- neurons demonstrate hyperpalmitoylation of GluN2B as well as Fyn kinase, which regulates surface retention of GluN2B. Thus, PPT1 plays a critical role in postsynapse maturation by facilitating the GluN2 subunit switch and proteostasis of palmitoylated proteins.