Limited Efficacy of Adipose Stromal Cell Secretome-Loaded Skin-Derived Hydrogels to Augment Skin Flap Regeneration in Rats.

Insufficient vascularization is a recurring cause of impaired pedicled skin flap healing. The administration of adipose tissue-derived stromal cells' (ASCs') secretome is a novel approach to augment vascularization. Yet, the secretome comprised of soluble factors that require a sustained-release vehicle to increase residence time. We hypothesized that administration of a hydrogel derived from decellularized extracellular matrix (ECM) of porcine skin with bound trophic factors from ASCs enhances skin flap viability and wound repair in a rat model. Porcine skin was decellularized and pepsin-digested to form a hydrogel at 37°C. Conditioned medium (CMe) of human ASC was collected, concentrated 20-fold, and mixed with the hydrogel. Sixty Wistar rats were included. A dorsal skin flap (caudal based) of 3 × 10 cm was elevated for topical application of DMEM (group I), a prehydrogel with or without ASC CMe (groups II and III), or ASC CMe (group IV). After 7, 14, and 28 days, perfusion was measured, and skin flaps were harvested for wound healing assessment and immunohistochemical analysis. Decellularized skin ECM hydrogel contained negligible amounts of DNA (11.6 ± 0.6 ng/mg), was noncytotoxic and well tolerated by rats. Irrespective of ASC secretome, ECM hydrogel application resulted macroscopically and microscopically in similar dermal wound healing in terms of proliferation, immune response, and matrix remodeling as the control group. However, ASC CMe alone increased vessel density after 7 days. Porcine skin-derived ECM hydrogels loaded with ASC secretome are noncytotoxic but demand optimization to significantly augment wound healing of skin flaps.

Extracellular Matrix-Derived Hydrogels to Augment Dermal Wound Healing: A Systematic Review.

Chronic, non-healing, dermal wounds form a worldwide medical problem with limited and inadequate treatment options and high societal burden and costs. With the advent of regenerative therapies exploiting extracellular matrix (ECM) components, its efficacy to augment wound healing is to be explored. This systematic review was performed to assess and compare the current therapeutic efficacy of ECM hydrogels on dermal wound healing. The electronic databases of Embase, Medline Ovid, and Cochrane Central were searched for in vivo and clinical studies on the therapeutic effect of ECM-composed hydrogels on dermal wound healing (April 13, 2021). Two reviewers selected studies independently. Studies were assessed based on ECM content, ECM hydrogel composition, additives, and wound healing outcomes, such as wound size, angiogenesis, and complications. Of the 2102 publications, 9 rodent-based studies were included while clinical studies were not published at the time of the search. Procedures to decellularize tissue or cultured cells and subsequently generate hydrogels were highly variable and in demand of standardization. ECM hydrogels with or without additives reduced wound size and also seem to enhance angiogenesis. Serious complications were not reported. To date, preclinical studies preclude to draw firm conclusions on the efficacy and working mechanism of ECM-derived hydrogels on dermal wound healing. The use of ECM hydrogels can be considered safe. Standardization of decellularization protocols and implementation of quality and cytotoxicity controls will enable obtaining a generic and comparable ECM product. Impact statement Extracellular matrix (ECM)-based hydrogels are biocompatible and harbor growth factors that can instruct tissue healing. Their application is a novelty in (pre)clinical wound healing treatment. This systematic review provides an overview of the current evidence for ECM hydrogels in enhancing wound healing and an extensive overview of the decellularization procedures used. Lastly, challenges and future directions to standardize decellularization procedures and implement quality controls are proposed.

Postoperative Renal Function in Patients Undergoing Unilateral Nephrectomy: Development of a Prediction Model Using Preoperative Risk Factors and 51Cr-EDTA Clearance.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the reference isotopic technique 51Cr-ethylene diamine tetra-acetic (51Cr-EDTA) and to create a model to predict the short-term postoperative GFR. Secondary aim was to evaluate which of the common equations for GFR estimation (Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) has the best correlation with the 51Cr-EDTA. Methods: Patients undergoing unilateral nephrectomy from 2014 to 2018 were selected. Pre- and postoperative variables were prospectively collected. Univariate and multivariate analyses were done to identify independent risk factors associated with renal function outcomes and to create a model to predict the postoperative GFR. Correlation analyses were performed to evaluate the performance of various serum creatinine-based equations for GFR estimation compared with 51Cr-EDTA. Results: In total, 107 patients were evaluated. After univariate and multivariate analyses, older age (p = 0.008), higher split function of the operated kidney on dimercaptosuccinic acid (DMSA) scintigraphy (p < 0.001), and lower preoperative 51Cr-EDTA (p < 0.001) were independent risk factors for higher GFR decline. Correlation analyses showed that GFR estimated by CKD-EPI equation had the best concordance to GFR measured by 51Cr-EDTA. Conclusions: Based on our findings age, DMSA and lower preoperative 51Cr-EDTA are predictors of postoperative renal function after unilateral nephrectomy. For the assessment of estimated GFR, CKD-EPI equation appears to have the best concordance with 51Cr-EDTA.

Tratamento cirúrgico combinado de endocardite do átrio direito por aspergillus sp e de bola fúngica pulmonar: relato de caso / Combined surgical treatment of endocarditis of the right atrium due to aspergillus sp and pulmonary emboli: a case report

A endocardite por aspergillus é rara e de alta mortalidade. Apresentamos o caso de um paciente de 23 anos portador da síndrome Kipple-Trenaunay que apresentou quadro de dispnéia aos grandes esforços e emagrecimento. Ao exame físico apresentou à ausculta cardíaca desdobramento variável de B2 e estalido protossistólico. Ao exame radiológico de tórax apresentava lesöes cavitárias múltiplas com aspecto areolar em lobo superior direito e velamento do seio costofrênico esquerdo. O ecocardiograma e a avaliaçäo hemodinâmica evidenciaram imagem sugetiva de tumor em átrio direito. O paciente foi operado sob circulaçäo extracorpórea, foi aberto o átrio direito, retirou-se uma vegetaçäo na válvula da veia cava inferior e no pulmäo foi ressecada lesäo friável de lobo superior direito. Ao exame anátomo-patológico foi diagnositcado aspergiloma. O paciente evoluiu bem recebendo alta no 13§ dia pós-operatório. Está assintomático no 65§ mês pós-operatório