Venous leg ulcers (VLUs) are the most common type of leg ulcers with a significant socioeconomic burden due to slow healing. Cytokines may be involved in the pathogenesis of VLUs. In this systematic review, our objective was to investigate the association between cytokine levels, including growth factors, with the healing of VLUs. PubMed, Embase, Web of Science and Cochrane Library were searched from their inception to August 2021. We retrieved 28 articles investigating 38 different cytokines in 790 patients. Cytokines were most commonly investigated in wound fluid and less frequently in biopsies and serum. The studies were judged as having a moderate to high risk of bias, and the results were often inconsistent and sometimes conflicting. A meta-analysis was not performed due to clinical and methodological heterogeneities. We found weak evidence for elevated IL-1α, IL-6, IL-8, TNF-α and VEGF levels in non-healing VLUs, an elevation that declined with healing. TGF-β1 levels tended to increase with VLU healing. Other cytokines warranting further investigations include EGF, FGF-2, GM-CSF, IL-1β, IL-1Ra and PDGF-AA/PDGF-BB. We conclude that non-healing VLUs may be associated with an elevation of a palette of pro-inflammatory cytokines, possibly reflecting activated innate immunity in these wounds. There is a paucity of reliable longitudinal studies monitoring the dynamic changes in cytokine levels during wound healing.

BackgroundIncident atrial fibrillation (AF) is reported in 10%–65% of patients without previous AF diagnosis after open heart surgery. The risk of late AF recurrence after a postoperative AF onset is unclear, and it is controversial whether AF limited to the postoperative period should elicit oral anticoagulation (OAC) therapy. The primary objective of this study was to evaluate the long-term recurrence of AF in patients developing new-onset peri-procedural AF.Patients and methodsPatients (n=189) with available baseline and follow-up data included in Left Atrial Appendage Closure with Surgery trial were coded for known AF at baseline and for postoperative first-time AF diagnosis. AF occurrence was classified as follows: peri-procedural ≤7 days postoperatively, early >7 days but ≤3 months and late >3 months. Patients with no AF recurrence registered during follow-up were invited to undergo Holter monitoring.ResultsA total of 163 (86.2%) patients had no history of AF. Among these, 80 (49.1%) developed new-onset peri-procedural AF. After a mean follow-up of 3.7±1.6 years, late AF occurred in 35 of the 80 (43.8%) patients who developed peri-procedural AF and in 6 additional patients (7.2%) who remained in sinus rhythm until discharge (hazard ratio [HR] 9.3, 95% CI 3.8–22.4, p<0.001). Patients with peri-procedural AF and early AF had 12.24 times higher risk of late AF (95% CI 4.76–31.45, p<0.001) as compared to the group with no postoperative AF.ConclusionNew-onset of AF after open heart surgery has a high rate of recurrence and should not be regarded as a self-limiting phenomenon secondary to surgery.

Acute wounds may require cleansing to reduce the risk of infection. Stabilized hypochlorous acid in acetic buffer (HOCl + buffer) is a novel wound irrigation solution with antimicrobial properties. We performed a first-in-man, prospective, open-label pilot study to document preliminary safety and performance in the treatment of acute wounds. The study enrolled 12 subjects scheduled for a split-skin graft transplantation, where the donor site was used as a model of an acute wound. The treatment time was 75 s, given on 6 occasions. A total of 7 adverse events were regarded as related to the treatment; all registered as pain during the procedure for 2 subjects. One subject had a wound infection at the donor site. The mean colony-forming unit (CFU) decreased by 41% after the treatment, and the mean epithelialization was 96% on both days 14 (standard deviation [SD] 8%) and 21 (SD 10%). The study provides preliminary support for the safety, well-tolerance, and efficacy of HOCl + buffer for acute wounds. The pain was frequent although resolved quickly. Excellent wound healing and satisfying antimicrobial properties were observed. A subsequent in vitro biofilm study also indicated good antimicrobial activity against Pseudomonas aeruginosa with a 96% mean reduction of CFU, when used for a treatment duration of 15 min ( P < .0001), and a 50% decrease for Staphylococcus aureus ( P = .1010). Future larger studies are needed to evaluate the safety and performance of HOCl + buffer in acute wounds, including the promising antimicrobial effect by prolonged treatment on bacterial biofilms.

The aim of this randomized controlled trial was to evaluate the wound-healing effect and antimicrobial properties of a novel stabilized hypochlorous acid solution on acute wounds, using a suction blister wound model. One suction blister was raised and de-roofed on each forearm in 20 healthy volunteers. Stabilized hypochlorous acid/control (sterile 0.9% NaCl) solutions were assigned to either wound by concealed randomization. Wounds were irrigated and treated on days 0, 2 and 4. Re-epithelialization was assessed blindly by digital planimetry, and bacterial growth was assessed as the number of colony-forming units cultured from surface swabs. Hypochlorous acid solution increased the degree of re-epithelialization on day 4 by 14% compared with the control solution (95% confidence interval (CI) 6.8–20%, p = 0.00051) and was not inferior (p < 0.0001) to the control solution on day 10 (0.3%, 95% CI –1.3–1.9%). Median bacterial counts were lower with stabilized hypochlorous acid compared with control and were further reduced after irrigation and treatment of both groups on day 4, but remained lower in the stabilized hypochlorous acid group compared with the control group. This study demonstrates immediate and durable antimicrobial action and a beneficial effect on acute wound healing after irrigation and treatment with a stabilized hypochlorous acid formulation.