Serra 2013.

Methods	Prospective cohort Setting: single centre Country: Italy Duration of follow‐up: 8 weeks Treatments: all participants treated with appropriate surgery and compression (30‐40 mmHg)
Participants	31 participants with VLUs (study additionally reported on a group without ulcers) Mean age: 51.5 (SD 9) years, range 42‐61 years Sex (M:F): 9:22 Stage of ulcer: class 6 of CEAP (inclusion criterion) Ulcer duration: > 6 weeks (inclusion criterion) Ulcer size at baseline: median (range) 10.7 (2.1‐17.5) cm² Wound infection: no infection within 6 weeks (exclusion criterion) Number of wounds: 31 Inclusion criteria: aged 20‐70 years, VLU (class 6 CEAP), duration > 6 weeks, ABPI > 0.9 Exclusion criteria: arterial disease, infection within 6 weeks, connective tissue disorder, blood disorder, cancer
Prognostic factors	MMP‐9 (continuous data); ng/total sample protein (μg). Measurement method ELISA: substrate and optical density measurements. Reported as ng per total sample protein (μg) Time of measurement: baseline, within 24 hours of surgery at 4 weeks, 8 weeks Wound fluid sampling method: occlusive dressings (fluid collected after 4 hours)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Selection bias	Unclear risk	Moderate: sample selection not stated
Attrition bias	Low risk	No missing data
Prognostic factor measurement	Unclear risk	Moderate: unclear if ELISA is adequate method and unclear if active or latent protease
Outcome measurement	High risk	Not adjusted for baseline; unclear if blinded
Adjustment factors	High risk	None of the key adjustment factors taken into account in the design or analysis
Analysis and reporting	Unclear risk	Moderate: data extracted from graph
Overall risk of bias	High risk