This study is a retrospective study conducted in a single centre. Consecutive patients who referred to a tertiary level DFS serving Rome and Lazio, Italy since January 2019–May 2020 for a new active DFU were included in the study while patients with reduced life-expectancy (less than 6 months) were excluded (see Fig. 1).
All patients were managed by a pre-set limb salvage protocol following International Working Group on the Diabetic Foot (IWGDF) Guidance , including restoration of foot perfusion in the case of peripheral ischemia, antibiotic therapy (and surgery if required) in the case of infection, offloading of affected limb, management of diabetes and comorbidities, ulcer debridement, and local wound care based on the best evidence recommendations.
At the time of admission, demographic and clinical data as well as DFU characteristics were recorded. In addition, DFU’ severity and timing of referral were reported according to the FTP classification and recommendations.
Hypertension was considered in the case of current antihypertensive therapy; hypercholesterolemia was considered in the case of current statin therapy; ischaemic heart disease (IHD) was considered in the case of previous acute coronary syndrome or coronary revascularization, evidence of angina, significant changes on electrocardiography (above or under-levelling ST, q wave, inversion of T wave, new left bundle branch block). Cerebrovascular disease (CVD) was considered in the case of previous cerebrovascular ischemia, previous carotid revascularization, or significant carotid artery disease (occlusion > 70%). Dialysis was considered in the case of end-stage-renal-disease (ESRD) requiring renal replacement therapy.
Ulcer characteristics reported at the time of presentation, and first assessment at the MDFT. Deep ulcers were considered in the case of full thickness skin lesions, extending from the subcutaneous to tendon, muscle, or bone. Diagnosis of infection was defined according to IWGDF guidelines .
Standard treatment in the centre followed IWGDF guidelines with initial broad spectrum antibiotic therapy and then according on culture results if required . All patients received off-loading for relieving pressure and trauma in the ulcer area according both to ulcer location, the presence of both ischemia or infection (isolated or in conjunction) and individual needs .
The association of ischaemic, and ulceration was defined as either no palpable distal pedal pulses, TcPO2 < 30mmhg [4, 5] and/or arterial stenosis/occlusions documented by ultra-sound duplex or computed tomography or MRI requiring lower limb revascularization. The revascularization procedure was performed in respect to foot condition, vessels affected and patient’s general condition by either endovascular or surgical (by-pass) procedure [4, 6].
Assessment of DFU severity
DFU’ severity and timing of referral were classified according to FTP classification : uncomplicated DFUs were considered in the case of superficial, not infected, not ischaemic ulcers; complicated DFUs were considered in the case of ischaemic, infected (mild/moderate), deep (involving soft tissue and/or bone), or any kind of ulcers in patients on dialysis or with heart failure; severely complicated DFUs were considered in the case of abscess, wet gangrene, necrotizing fasciitis or in the case of fever or clinical signs of sepsis.
Assessment of referral timing
According to the timing of referral, patients were divided in two groups: early referral (ER) and late referral (LR). Based on the FTP recommendations , ER were considered patients who referred immediately after 2 weeks in the case of uncomplicated non-healing ulcers (reduction of ulcer size < 30% after 2 week of standard of care), within 4 days in the case of complicated ulcers and within 24 h in the case of severely complicated ulcers. LR patients were considered when the specific timing of referral for each grade of ulcer’ severity was not respected.
Completed ulcer healing, healing time, minor and major amputation, hospitalization, and survival after at least 6 months of follow-up were evaluated. Definitive ulcer healing was taken to be complete epithelialization of the target wound, and maintenance of the closed healed epithelized surface for a minimum of 2 weeks. Healing time was reported in weeks. Minor amputation was considered any amputation below-the-ankle (digital, ray, metatarsal, Lisfranc, Chopart). While, major amputation was considered any amputation above the ankle. Mortality for any cause was recorded.
Data are expressed as mean ± SD. Comparison between groups was reported using an X2 test (frequency data) or Student’s t test (continuous data). Univariable logistic regression analyses was performed for all potential predictor variables with the outcome of interest (major amputation and mortality), with values presented as univariable odds ratios (ORs) along with the respective 95% CI. Thereafter, all potential predictors were entered simultaneously into a multivariable logistic regression model. These models yielded a set of variables that best predict outcome. Statistical analysis was performed by SAS (JMP12; SAS Institute, Cary, NC) for the personal computer.