Background Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation. Methods Peripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is “cross talk” between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined. Results AATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs. Conclusions The expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.
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Background: Breast reductions, including oncoplastic breast surgery (OBS), have high postoperative wound healing complication (WHC) rates, ranging from 17% to 63%, thus posing a potential delay in the onset of adjuvant therapy. Incision management with closed incision negative pressure therapy (ciNPT) effectively reduces postoperative complications in other indications. This retrospective analysis compares postoperative outcomes and delays in adjuvant therapy in patients who received ciNPT on the cancer breast versus standard of care (SOC) after oncoplastic breast reduction and mastopexy post lumpectomy. Methods: Patient demographics, ciNPT use, postoperative complication rates, and time to adjuvant therapy were analyzed from the records of 150 patients (ciNPT = 29, SOC = 121). Propensity score matching was used to match patients based on age, body mass index, diabetes, tobacco use, and prior breast surgery. Results: In the matched cohort, the overall complication rate of ciNPT-treated cancerous breasts was 10.3% (3/29) compared with 31% (9/29) in SOC-treated cancerous breasts (P = 0.096). Compared with the SOC-treated cancerous breasts, the ciNPT breasts had lower skin necrosis rates [1/29 (3.4%) versus 6/29 (20.7%); P = 0.091] and dehiscence rates [0/29 (0%) versus 8/29 (27.6%); P = 0.004]. In the unmatched cohort, the total number of ciNPT patients who had a delay in adjuvant therapy was lower compared to the SOC group (0% versus 22.5%, respectively; P = 0.007). Conclusion: Use of ciNPT following oncoplastic breast reduction effectively lowered postoperative wound healing complication rates and, most importantly, decreased delays to adjuvant therapy.
PSTM Top AbstractsCONCLUSION: Percentage of total sagittal suture fusion was not associated with CI or head shape in patients with non-syndromic sagittal craniosynostosis in this cohort. Decreased fusion of the anterior one-third of the sagittal suture was paradoxically associated with higher CI and more severe scaphocephalic head shape. These findings raise additional questions regarding suture fusion and head-shape morphology, and further research is needed to substantiate these results in patients with non-syndromic sagittal craniosynostosis. These findings may have implications for understanding suture fusion patterns in other variations of craniosynostosis.
OBJECTIVE:The management of cranioplasty infections has historically been explantation followed by delayed reimplantation/reconstruction. This treatment algorithm necessitates surgery, tissue expansion, and prolonged disfigurement. In this report, the authors describe a treatment approach consisting of serial vacuum-assisted closure (VAC) with hypochlorous acid (HOCl) solution (Vashe Wound Solution; URGO Medical) as a salvage strategy. METHODS:A 35-year-old man who sustained head trauma, neurosurgical complications, and severe syndrome of the trephined (SOT; devastating neurologic decline treated by cranioplasty) underwent titanium cranioplasty with free flap. Three weeks postoperation, he presented with pressure-related wound dehiscence/partial flap necrosis, exposed hardware, and bacterial infection. Given the severity of his precranioplasty SOT, hardware salvage was critical. He was treated with serial VAC with HOCl solution for 11 days followed by VAC for 18 days and definitive split-thickness skin graft placement over resulting granulation tissue. Authors also conducted a literature review of cranial reconstruction infection management. RESULTS:The patient remained healed 7 months postoperatively without recurrent infection. Importantly, his original hardware was retained, and his SOT remained resolved. Findings from the literature review support the use of conservative modalities to salvage cranial reconstructions without hardware removal. CONCLUSIONS:This study investigates a new strategy for managing cranioplasty infections. The VAC with HOCl solution regimen was effective in treating the infection and salvaging the cranioplasty, thus obviating the complications associated with explantation, new cranioplasty, and recurrence of SOT. There is limited literature on the management of cranioplasty infections using conservative treatments. A larger study to better determine the efficacy of VAC with HOCl solution is underway.
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