Risk factors for sternal wound infection after open-heart operations: A systematic review and meta-analysis.

We aimed to quantitatively and systematically elucidate the rationality of the examined variables as independent risk factors for sternal wound infection. We searched databases to screen studies, ascertained the variables to be analysed, extracted the data and applied meta-analysis to each qualified variable. Odds ratios and mean differences were considered to be the effect sizes for binary and continuous variables, respectively. A random-effects model was used for these procedures. The source of heterogeneity was evaluated using a meta-regression. Publication bias was tested by funnel plot and Egger's test, the significant results of which were then calculated using trim and fill analysis. We used a sensitivity analysis and bubble chart to describe their robustness. After screening all variables in the eligible literature, we excluded 55 because only one or no research found them significant after multivariate analysis, leaving 33 variables for synthesis. Two binary variables (age over 65 years, NYHA class >2) and a continuous variable (preoperative stay) were not significant after the meta-analysis. The most robust independent risk factors in our study were diabetes mellitus, obesity, use of bilateral internal thoracic arteries, chronic obstructive pulmonary disease, prolonged surgery time, prolonged ventilation and critical preoperative state, followed by congestive heart failure, atrial fibrillation, renal insufficiency, stroke, peripheral vascular disease and use of an intra-aortic balloon pump. Relatively low-risk factors were emergent/urgent surgery, smoking, myocardial infarction, combined surgery and coronary artery bypass grafting. Sternal wound infection after open-heart surgery is a multifactorial disease. The detected risk factors significantly affected the wound healing process, but some were different in strength. Anything that affects wound healing and antibacterial ability, such as lack of oxygen, local haemodynamic disorders, malnutrition condition and compromised immune system will increase the risk, and this reminds us of comprehensive treatment during the perioperative period.

Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway.

Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this study, Kunming (KM) mice were used to set up a wound model. All the mice were randomly divided into the control, the local treatment with saline group, the local treatment with the hydrogen-rich saline group, and the intraperitoneal injection of the hydrogen-rich saline group. To evaluate the impact of hydrogen-rich saline on wound healing, we assessed the wound healing rate, wound closure time, histomorphology, oxidative stress indicators, inflammatory cytokines, the apoptosis index, and the expression of the nuclear factor-erythroid-related factor 2(Nrf-2). Furthermore, the immortalized nontumorigenic human epidermal (HaCaT) cells were chosen to investigate the therapeutic effects of hydrogen-rich medium on oxidative stress and its underlying mechanisms. The results showed that local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation. Meanwhile, it decreased the cell apoptosis index and increased the Nrf-2 expression. Besides, hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway. In conclusion, local treatment of hydrogen-rich saline exhibits the healing-promoting function through antioxidant, anti-inflammatory, and antiapoptotic effects. Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.

c-Casitas b-Lineage Lymphoma Downregulation Improves the Ability of Long-term Cultured Mesenchymal Stem Cells for Promoting Angiogenesis and Diabetic Wound Healing.

The chronic wound induced by diabetes has poor efficacy and could lead to amputation. The repair function of mesenchymal stem cells (MSCs) impaired after long-term culture in vitro. Studies have shown that the proto-oncogene c-Casitas b-lineage lymphoma (c-Cbl) can regulate receptor- and non-receptor tyrosine kinase, which was also involved in the angiogenesis process. This study aimed to explore the regulative effect of c-Cbl on the proangiogenic functions of long-term cultured MSCs and evaluate its pro-healing effect on diabetic wounds. In this study, the c-Cbl level was downregulated by locked nucleic acid-modified antisense oligonucleotide gapmers (LNA Gapmers). We detected the effect of c-Cbl downregulation on long-term cultured MSCs in terms of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal, cellular proliferation, senescence, migration, and angiogenic factors paracrine activity in vitro. In vivo, we observed the pro-healing effect of long-term cultured MSCs, with or without c-Cbl downregulation, on the diabetic wound. We found that the phosphorylation level of c-Cbl increased and that of Akt decreased in passage 10 (P10) MSCs compared with passage 3 (P3) MSCs (P < 0.05). Additionally, the proliferation, paracrine, and migration capacity of P10 MSCs decreased significantly, accompanied by the increase of cellular senescence (P < 0.05). However, these functions, including PI3K/Akt activity of P10 MSCs, have been improved by c-Cbl downregulation (P < 0.05). Compared with P10 MSCs treatment, treatment with c-Cbl downregulated P10 MSCs accelerated diabetic wound healing, as defined by a more rapid wound closure (P < 0.05), more neovascularization (P < 0.05), and higher scores of wound histological assessment (P < 0.05) in a diabetic rat model. Our findings suggested that c-Cbl downregulation could attenuate the impairment of proangiogenic functions in MSCs induced by long-term culture in vitro and improve the effect of long-term cultured MSCs in promoting diabetic wound healing.

Topical effect of benzalkonium bromide on wound healing and potential cellular and molecular mechanisms.

Benzalkonium bromide (BB) has been widely used as a skin antiseptic for wound management. However, BB had proinflammation and reactive oxygen species (ROS) induction effect, making its role in wound healing complex and unclear. A rat full-thickness skin defect wound model was established. The effects of BB, povidone iodine (PVP-I), chlorhexidine gluconate (CHG), and normal saline (NS) on wound healing and infection control were then evaluated based on wound healing rate (WHr) and bacterial killing. The wound tissues were sectioned for histopathological evaluation and nuclear factor E2 related factor 2 (Nrf2) expression determination. The ROS production, Nrf2 activation, and heme oxygenase 1 (HO-1) expression of the HaCat cells and the cytotoxicity treated with BB were further explored. Compared with NS, PVP-I, and CHG, BB showed the best wound infection control efficiency while delayed wound healing with the WHr of 91.42 ± 5.12% at day 20. The wound tissue of the BB group showed many inflammatory cells but few granulation tissue and capillaries and no obvious collagen deposition, resulting in the lowest histopathological scores of 4.17 ± 0.75 for BB group. BB showed higher cytotoxicity on HaCat cells with the lowest IC25, IC50, and IC75 of 1.90, 4.16, and 9.09 g/mL compared with PVP-I and CHG. TUNEL staining evaluated the cytotoxicity of BB on wound tissue, which indicates the high apoptosis index BB group (5.05 ± 1.77). Compared with PVP-I and CHG, BB induced much more cell apoptosis. The results of flow cytometry and fluorescence staining showed that PVP-I, CHG, and BB induced ROS production in a concentration-dependent manner and cells treated with BB had the highest ROS production at the same inhibition concentration. The cells and the wound tissues treated with BB showed highest Nrf2 activation and HO-1 expression than PVP-I and CHG. BB was highly efficient in wound infection control while delayed wound healing. The prolonged and strengthened inflammation and the raised ROS production originating from BB administration may contribute to delayed wound healing.