Monami Matteo, Scatena Alessia, Ragghianti Benedetta, Miranda Cesare, Monge Luca, Silverii Antonio, Uccioli Luigi, Vermigli Cristiana
Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy.
San Donato Hospital, Arezzo, Health Authorities South East Tuscany, Arezzo, Italy.
Acta Diabetol. 2024 Dec 26. doi: 10.1007/s00592-024-02426-7.
To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.
A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables.
Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate").
In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.
评估几种常用于治疗糖尿病足溃疡（DFU）的辅助治疗（AT）的效果。本荟萃分析旨在支持《意大利糖尿病足综合征治疗指南》的制定。
截至2024年5月20日，对Medline和Embase进行检索，收集所有纳入糖尿病患者的随机对照试验（RCT），或报告对患有DFU的糖尿病患者进行亚组分析的试验，这些试验将AT与安慰剂/标准治疗（SoC）进行比较，持续时间至少为12周。预先设定的终点指标为：溃疡愈合（主要指标）、愈合时间、大截肢和小截肢、严重不良事件（SAE）以及全因死亡率。评估的AT包括：生长因子（GF）、富血小板血浆和纤维蛋白（PRP/F）、皮肤替代物（SS）、负压伤口治疗（NPWT）和高压氧治疗（HBOT）。Mantel-Haenzel优势比和95%置信区间（MH-OR，95%CI）要么直接从出版物中计算得出，要么直接提取。对连续变量计算加权平均差和95%CI。
51项研究符合所有纳入标准（分别有3项、5项、27项、8项和8项研究涉及GF、PRP/F、SS、NPWT和HBOT）。与SoC/安慰剂相比，接受任何一种所探索的AT治疗的参与者溃疡愈合率显著更高（MH-OR范围为2.17至4.18），愈合时间更短。尽管SAE风险更高，但只有PRP/F和HBOT显示大截肢风险显著更低（MH-OR分别为0.32(0.11;0.93); p = 0.04和0.28(0.10;0.79); p = 0.02）。未观察到对上述预先设定的终点指标有其他显著影响。对于主要终点指标，除NPWT（“中等”）外，所有AT的证据质量均被评为“高”。
总之，AT可积极促进DFU患者的伤口愈合并缩短愈合时间。HBOT和PRP/F也显示出大截肢风险降低，尽管SAE发生率较高。
