Journal of Plastic, Reconstructive & Aesthetic Surgery (2011) 64, 867e872

A multidisciplinary diabetic foot ulcer treatmentprogramme significantly improved the outcome inpatients with infected diabetic foot ulcers

Chong-Chi Chiu a, Chen-Ling Huang b, Shuen-Fu Weng b, Lei-Ming Sun c,Yu-Lien Chang d, Feng-Chou Tsai c,*

aDepartment of General Surgery, Chi-Mei Medical Center, Chia Nan University of Pharmacy and Science, Tainan,Taipei Medical University, TaiwanbDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital,Taipei, TaiwancDivision of Plastic Surgery, Department of Surgery, Center for Mathematical Biology, Taipei Medical University Hospital,Taipei Medical University, Taipei, TaiwandDivision of Cardiovascular Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan

Received 10 June 2010; accepted 30 November 2010

KEYWORDSDiabetes;Foot ulcer;Amputation;Flap;Programmes

* Corresponding author. Present addþ886 2 27389524.

E-mail address: biopattern@gmail.

1748-6815/$-seefrontmatterª2010Bridoi:10.1016/j.bjps.2010.11.024

Summary Background: Diabetic foot ulcers (DFUs) superimposed by infection and ischaemiamay result in amputation without prompt and adequate management. We investigatedwhether the diabetic foot ulcer treatment programme (DFUTP) involving immediate debride-ment within 12 h, flap coverage and/or revascularisation improved the outcome of patientswith infected DFUs.Method: Between 2006 and 2009, we randomly enrolled 350 patients in the DFUTP group andcompared them with control patients (the non-DFUTP group, n Z 386) in Taiwan. Inclusioncriteria consisted of infected diabetic foot ulcers with or without ischaemia. The risk factors,dynamics and outcome of amputation and re-amputation were analysed in terms of patientdemographics, glycaemic control and infection.Result: The results of logistic regression analyses indicated that risk factors of amputation inboth groups were HbA1c (odds ratio (OR)Z 1.63, 95% confidence interval (CI) 1.31e2.02) and Creactive protein (OR Z 1.12, 95% CI 1.01e1.24). The DFUTP group showed a lower amputationrate than the non-DFUTP group (p Z 0.001). The association between the amputation andUniversity of Texas (UT) classification was not statistically significant. The KaplaneMeier esti-mate showed that the time to complete recovery of the sugar level in the DFUTP group wasfaster than in the non-DFUTP group (p Z 0.001). For patients at stage D, the hospital stayin the non-DFUTP group was longer than in the DFUTP group (p Z 0.014).

ress. 201, Taikang Village, Liou Ying Township, 736 Tainan, Taiwan. Tel.: þ886 2 27372181x3918; fax:

com (F.-C. Tsai).

tishAssociationofPlastic,ReconstructiveandAestheticSurgeons.PublishedbyElsevierLtd.All rightsreserved.

868 C.-C. Chiu et al.

Conclusion: The DFUTP provides an effective treatment programme for decreasing the ampu-tation rate with infected DFUs. Immediate debridement and flap reconstruction decrease theamputation and re-amputation rate respectively.ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published byElsevier Ltd. All rights reserved.

Randomised controlled trials for diabetic foot ulcers (DFUs)that focussed specifically on the secondary wound care havebeen published previously, and while the results seemedcompelling, the benefits were inconsistent.1�4 It is question-able whether the decreased amputation and re-amputationrates canbeattributed topassive treatmentandguidelines.5�9

Studies on aggressive treatment profiles are relatively rare inthe literature. We advocate an aggressive plan (diabetic footulcer treatment programme, DFUTP) developed by our plasticsurgeons with the goal of reducing the amputation rate.

First, infection aggravates the ischaemic and immuno-compromised portions of DFUs. Here, debridement canincrease the rate of limb salvage to 89.8% after 1 year.10

Delayed surgical management plays a key role for thesereasons: (1) the patient’s personal consideration on thesurgical risks at the first visit, (2) the limitations of hospitalfacilities orpolicies, and (3) delayeddiagnosis of infection andischaemia. Immediate debridement should therefore beperformed as soon as possible to decrease tissue destruction.

Second, angioplasty, stenting and endovascular athe-rectomy are methods of revascularisation that, if unsuc-cessful, can be followed by distal arterial bypass.11

Peripheral bypass can treat long arterial occlusions butcan still obtain poor outcomes if the occlusion is distributedextensively over the distal end of foot arteries.12,13 DFUTPnot only passively reanalyzes the vascular insufficiencythrough revascularisation but also actively nourishes thepoorly vascularised recipient site via the flap.14�17 Insummary, our treatment principle for DFUs can be sum-marised by promptness, completeness and minimal delays.Our study sought to analyse whether the early interventionby a plastic surgeon and DFUTP may yield better results.

Variouswoundclassification systemshavebeen introducedto describe the characteristics of DFUs.18,19 The mainparameters that influence the outcome in the widely usedWagner and UT diabetic wound classification system areinfection, ischaemia and wound depth as shown in Table1.20,21 The severe DFU wounds with infection and ischaemiaare always challenging. In this case-control study, the UTwound classification system was used because literaturesuggests it provides a better predictor of outcome and treat-ment-oriented assessment.22 We then assessed whetherDFUTP could reduce the amputation and re-amputation ratesof infected DFUs with or without ischaemia when comparedwith conventional treatment programmes. Finally, we ana-lysed not only the risk factors of amputation but also pre-sented the dynamics of the disease course in both groups.

Patients and methods

The institutional review board of the Taipei MedicalUniversity Hospital involved in the DFUTP study approvedthe treatment programme (TMUH-01-09-11). A total of18,084 patients were identified with Type II diabetes at the

Taipei Medical University Hospital between January 2000and January 2009. The patients were initially treated in thediabetic outpatient services for diabetic control at eachvisit. The inclusion criteria of patients with infected DFUsfor admission and follow-up in this case-control study,based on the UT classification system, were (1) stage B(non-ischaemic infected wounds) or D (ischaemic infectedwounds), (2) wound depth with a severity higher than grade2 (wound penetrating the tendon or capsule) and (3) woundarea larger than 3 � 3 cm.

The DFUTP was developed in 2003 to treat DFUs at ourhospital as shown in Figure 1. By comparison, doctors forthe non-DFUTP control group were given no specificguidelines for deciding on the timing of debridement andselection of conventional wound treatments. The data setof the non-DFUTP group was then collected retrospectively.As many as 800 patients were randomly selected in bothintervention groups to decrease selection bias and increaseinternal validity. Follow-up continued until the woundhealed or amputation. For personal reasons, 64 patients(64/800, 8%) failed to complete the follow-up programme.Finally, patients in the DFUTP group (n Z 350, 2004e2009)were prospectively enrolled for comparison with patients inthe controls (non-DFUTP cohort group, n Z 386,2000e2003) for the conclusion of the study. We selectedsubjects who were statistically match with the study cohortto minimise the selection bias in terms of demographicprofiles, medical history, laboratory and examination data.

Patients in the DFUTP group were surveyed and cared forby the experienced specialists (endocrinologists, vascularsurgeons and plastic surgeons). When the infection(particularly abscess) was superimposed on DFUs, purulentdischarges were drained and the devitalised tissues debri-ded within 12 h, even if it was necessary to perform surgeryemergently. Once the symptoms and signs of infectionsubsided, revascularisation (angioplasty or bypass) wasperformed when required. Flap reconstruction was used forwound coverage and nourishing the vascularised tissue. Theprimary choice for the free flap was the free anterolateralthigh flap, harvested from the healthy thigh contralateralto the site of the DFU. End-to-side microsurgical anasto-mosis between the free flap and recipient vessels wasperformed to maintain the original blood supply. Thesecondary choice was a local musculocutaneous flap.

Data were collected from files or over the phone bya research nurse specialist. Assessment during admissionincluded age, gender, body mass index (BMI), medicalhistory, blood pressure, hospital stay, pretreatment trans-cutaneous oxygen tension (TcPO2), parameters of diabetescontrol andparameters of infection.23 Body temperatureandwhite blood cell count (WBC) were recorded daily in thewards. C reactive protein (CRP) and HbA1c were recordedevery 6 days. TcPO2 was measured by an electrochemicaltransducer (Oxykapnomonitor, SMK 363; Hellige, Freiburg

Table 1 University of Texas (UT) classification.

Grade

0 Pre- or post-ulcerative site that has healed1 Superficial wound not involving tendon,

capsule, or bone2 Wound penetrating to tendon or capsule3 Wound penetrating to bone or joint

Stage

A Clean woundsB Nonischemic infected woundsC Ischaemic noninfected woundsD Ischaemic infected wounds

A multidisciplinary diabetic foot ulcer treatment programme 869

im Breisgau, Germany) fixed to the skin with double-sided adhesive rings. The days to complete recovery wereused to analyse the dynamics of the DFU course (normalvalue: fasting plasma glucose (FPG, below126mgdl�1); bodytemperature <37.5 �C and WBC < 10,000 ml). Wound depthwas evaluated using a sterile cotton swab. Ulcers werelabelled as infected if a purulent discharge was present with

Figure 1 Study profile of the DFUTP. Decision algorithm forthe patients with infected DFUs enrolled and followed-up inTaipei Medical University Hospital.

two other local signs (warmth, erythema, lymphangitis,oedema and pain). The diagnosis of lower extremity vascularinsufficiency was made on the basis of an ankle-brachialpressure index (ABI) <0.9. The amputation and re-amputa-tion episode was defined as the removal of any bone of thefeet and higher pre-amputation level (at least BK (belowknee) amputation), respectively.

Statistical analysis

Continuous variables, such as the patient’s age, were sum-marised for the population using descriptive statistics(number and standard deviation) and compared betweengroups with a two-sample t-test. Categorical variables, suchas medical history, were compared between treatmentprogrammes by the use of the two-tailed Fisher’s exact test.Risk factors were summarised by treatment assignment andcompared between the groups. Odds ratio (OR) was assessedusing the multivariate logistic regression method. We ana-lysed the data using a time-to-event strategy withKaplaneMeier estimates, followed by the log-rank (Man-teleCox) test. The statistical method provides a comparisonof the distribution and the disease’s course of events. Basedon a power of 80% and a significance level of 5%, we calcu-lated that a minimum sample size of 150 patients would beneeded to detect a significant difference in the proportions.To ensure adequate power for the assessment, enrolmentcontinued until the minimum target sample size was excee-ded by about 130%. All statistical calculations were per-formed using Statistical Package for Social Sciences (SPSS)15.0. Statistical significance was set for p < 0.05.

Results

The distributions of population characteristics are shown inTable 2. The risk factors relating to the amputation in bothgroups were HbA1c and CRP (OR Z 1.63, 95% confidenceinterval (CI) 1.31e2.02 vs. 1.12, 95% CI 1.01e1.24,respectively). The risk factor of amputation in the DFUTPgroup was only HbA1c (OR Z 1.72, 95% CI 1.15e2.58), butthose in the non-DFUTP group were HbA1c and CRP(OR Z 2.50, 95% CI 1.45e4.31 vs 1.29, 95% CI 1.03e1.61,respectively). We failed to find significant associationsbetween amputation and UT classification (stage and grade)in both groups. The OR for the amputation when the DFUTPgroup was compared with the non-DFUTP group was 2.89(95% CI 1.28e6.53). After stratification, stage D patients inthe DFUTP group had a lower amputation rate than those inthe non-DFUTP group (OR Z 2.91, 95% CI 1.03e8.22). Agreater proportion of patients in the non-DFUTP groupexperienced amputation compared with the DFUTP group(91 (23.6%) vs. 34 (9.7%), p < 0.001, Figure 2). Eleven (3.1%)of the 350 patients in the DFUTP group achieved a lower re-amputation rate than 28 (7.3%) of 386 patients in the non-DFUTP group during a 5-year follow-up (p Z 0.204). Thelikelihood of need for re-amputation for patients treated inthe DFUTP group decreased to less than half OR as likely asthe non-DFUTP group (0.425, 95% CI 0.11e1.65). Patients inthe non-DFUTP group received higher-level re-amputation(n Z 28) as follows: above-knee (8, 28.6%), BK (18, 64.3%)and toe (2, 7.1%) re-amputations. In comparison, there

Figure 2 Patients showed a lower amputation and re-amputation rate in the DFUTP group than in the non-DFUTPgroup.

870 C.-C. Chiu et al.

were only toe (8, 72.7%) and BK re-amputations (3, 27.3%)in the DFUTP group (n Z 11).

Figures 3 and 4 showed the days until the parameters ofpatients in both groups achieved complete recovery to thenormal value. Mean time to complete recovery of fever,leucocytosis, CRP and FPG were 6.4 � 0.1, 16.6 � 0.5,19.1 � 0.6, 30.6 � 0.8 days in the DFUTP group, and6.2 � 0.2, 16.0 � 0.7, 20.0 � 0.8 and 40.0 � 1.5 days in thenon-DFUTP group, respectively. The log-rank test for abovefour parameters showed that only the sugar level in theDFUTP group provided a faster recovery or relative stabilityof the disease course compared with the non-DFUTP group(p < 0.001).

Of the DFUTP patients, 350 (100%) patients had immediatedebridement, 161 (46%) had free flap reconstruction, 189(54%) had local flap reconstruction and 42 (12%) had revascu-larisation procedures. By contrast, management in the non-DFUTP group included healing by secondary wound intention(45, 11.6%), negative pressure wound therapy (41, 10.6%),revascularisation (56, 14.5%) and skin grafts (300, 77.8%).

The mean operative times for debridement and flapreconstruction in the DFUTP group were 28.4 min and 5 h15 min, respectively. The most commonly reported adverseeventwaspartialflapnecrosis (nZ10, 2.8%).Nonehada totalflap loss. The mean onset of these events was 6.2 days(SD Z 2.1). The flaps (n Z 95, 27.1%) received secondarythinning procedures to decrease their bulk and allow shoesfitting. Infections included monomicrobial (85, 11.5%) andpolymicrobial (651, 88.5%) in both groups (n Z 736). For thepatients receiving amputation after treatments, the ampu-tation levels in the DFUTP and non-DFUTP groups were toe(92%, 63%), BK (7%, 25%) and above-knee (1%, 12%). Therewas

Table 2 Population characteristics

DFUTP group (n Z 3

Demographic profileAge 62.3 � 7.6Gender (male/female) 189/161Body mass index 30.7 � 4.9Diabetes duration (years) 14 � 12.2UT classificationB 188D 162

Medical history (%)Congestive heart failure 5.1Myocardial infarction 6.4Renal dysfunction 1.7Smoking 57.2

Pre-operative laboratory and examination dataHbA1c 9.13 � 3.47CRP 12.21 � 7.10WBC 13,219.95 � 3903.21Blood sugar 264.01 � 81.25Ankle-brachial index (ABI) 0.88 � 0.13Systolic blood pressure (mm Hg) 136 � 18Diastolic blood pressure (mm Hg) 78 � 11Albumin (g/l) 31 � 4.2Pretreatment TcPO2 (mm Hg) 27 � 11

Data are mean � SD; NS Z not significant.

no statistical significance (pZ 0.188) in hospital staybetweentheDFUTP(23.5�5.8days)andnon-DFUTPgroup (29.3�17.9days).However, therewasa statistically significantdifferencein hospital stay for stage D patients between the DFUTP group(24.5 � 6.4 days) compared with the non-DFUTP group(33.8 � 19.9 days) (pZ 0.014).

Discussion

After the comparison group was selected, our case-controlstudy was matched for demographic profile, medical

50) Non-DFUTP group (n Z 386) p-value

64.1 � 7.7 NS210/176 NS28.2 � 6.3 0.02520 � 9.3 0.011

201 NS185

4.8 NS6.3 NS1.3 NS63.2 NS

8.01 � 3.44 NS10.69 � 7.09 NS14,590.39 � 6077.47 <0.01267.68 � 84.24 NS0.84 � 0.12 NS138 � 15 NS80 � 9 NS30 � 5.4 NS29 � 9 NS

Figure 3 KaplaneMeier estimates for time to completerecovery in the DFUTP group (fever, leukocytosis, CRP andFPG). Fever showed a faster recovery within one week afterimmediate and adequate debridement.

A multidisciplinary diabetic foot ulcer treatment programme 871

history, laboratory and examination data. The results of theDFUTP had unique characteristics that differentiated itfrom previous trials and prospective cohort studies in thetreatment of severe DFUs:

(1) Performing debridement within 12 h, even if emergently,yielded a lower amputation rate, a lower re-amputationrate and faster time to recovery of the sugar level.Treatmentprioritywasaimedat theeradicationofabscessand necrotising fasciitis using debridement. Variousmethods of debridement are recommended in the litera-ture.24,25 Fever subsidedwithin 1week after debridement

Figure 4 KaplaneMeier estimates for time to completerecovery in the non-DFUTP group showed a larger data variancein four parameters than the DFUTP group. The time tocomplete recovery of the sugar level in the DFUTP group wasfaster than in the non-DFUTP group (p < 0.001).

in both groups, according to the KaplaneMeier estimates.Leucocytosis and CRP subsequently returned to normal atabout 20 days and sugar (FPG) about 40days, in that order.The results verified that deterioration due to infectioncould be retarded in both the DFUTP and non-DFUTPgroups. Only the sugar level showed significantly fasterrecovery time after DFUTP. The DFUTP makes the gly-caemic control easier and faster, useful information tohave when making a clinical judgement.

(2) Poor glycaemic control and severe infection were riskfactors for amputation. HbA1c (OR Z 1.63) was a moreimportant risk factor than CRP (OR Z 1.12) in bothgroups. High preoperative HbA1c in particular was theonly risk factor in the DFUTP group. In other words, theinitial episode of infective DFUs under poor or no gly-caemic control despite aggressive treatments resultedin a poor outcome. Thus, adequate diabetic control iscrucial to the outcome of severe DFUs. These twopoints indicated that good outcome resulted in goodglycaemic control and vice versa.

(3) Patients at stage D in the DFUTP group had a loweramputation rate than patients in the non-DFUTP group(p Z 0.043), but aggressive treatment for stage Bshowed no statistically significant difference. The mostaggressive treatment programmes (flap coverage andrevascularisation) improved the salvage rate for themost severe DFUs. Diabetes gradually cause occlusalchanges to foot microcirculations and decreasedgeneral immunity. Devitalised tissues due to theischaemia can delay wound healing, increase predis-position to secondary infection and interfere withadequate assessment. Thus, ischaemic tissues shouldbe debrided immediately.

(4) Another finding was that flap coverage not onlydecreased the re-amputation rate but also lowered there-amputation level. Early and optimal wound coverageis always best for any wound. Flap reconstruction forinfected and ischaemic DFUs provides additionaladvantages: nourishing the distal ischaemic portion ofa foot lacking collateral circulation that a revascular-isation procedure could not successfully reach, aidingin resistance to infection, filling the defect afterdebridement, resistance to shearing force duringwalking, and protection from trauma. Until recently,there has been a tendency among doctors to selecta secondary intention or conventional wound caremethod to treat DFUs due to the risks of long operatingtimes, age, facility limitations and co-morbidities.Although randomised controlled trials have shown thatwound-care methods such as negative pressure woundtherapy improve DFU healing capacity, these methodsare highly dependent on an adequate blood supply anda clean wound base at the recipient site.26 Our resultsverified that the DFUTP group experienced a signifi-cantly decreased level of re-amputation (almost at thetoe level) with no extension to the BK or above-kneeamputation over a 5-year follow-up period.

(5) There was no significant association between amputa-tions and the UT classification in both groups unlikeprevious reports in the literature. In other words, anaggressive treatment plan can alter the poor outcomepreviously predicted by the classification system.

872 C.-C. Chiu et al.

(6) There was no statistically significant difference inhospital stay between either groups. This might bebecause flap reconstruction required longer hospitalstays than skin grafts, although no other delayedprocedures were noted in the DFUTP group.

(7) Our study indicated that DFUs not only benefited fromearly and aggressive intervention, but also thata plastic surgeon in charge of DFUTP effectivelydecreased the amputation rate of DFUs.

Several points should be noted when interpreting theresults of this study. The difficulty with adequately maskingDFU assessment from patients and surgeons produced thepotential for performance bias. Our study relied on datafrom a single hospital and plastic surgeon so it may not besufficiently representative for unequivocal conclusions tobe drawn. It may be possible to decrease the bias by usingmultiple hospitals due to different treatment policies andsurgeon experiences. We also analysed exact laboratorydata instead of simple categorized factors (medical history)and compromised findings.

In summary, our results indicated that DFUTP is aneffective treatment plan for infected DFUs. When thephysician is faced with DFUs, a more aggressive and rapidmanagement approach significantly reduces the chance andlevel of both amputation and re-amputation.

Conflict of interest

None.

Acknowledgement

This research project was supported by the Chi Mei Foun-dation Hospital (CMFH) under Grant No: 97CM-TMU-05.

References

1. Boyko EJ, Ahroni JH, Stensel V, et al. A prospective study of riskfactors for diabetic foot ulcer. Diabetic Care 1999;22:1036e42.

2. Armstrong DG, Lavery LA. Negative pressure wound therapyafter partial diabetic foot amputation: a multicentrerandomized controlled trial. Lancet 2005;266:1704e10.

3. Litzelman DK, Slemenda CW, Langefeld CD, et al. Reduction oflower extremity clinical abnormalities in patients with non-insulin-dependent diabetes mellitus: a randomized, controlledtrial. Ann Intern Med 1993;119:36e41.

4. Ennis WJ, Foremann P, Mozen N, et al. Ultrasound therapy forrecalcitrant diabetic foot ulcers: results of a randomized,double-blinded, controlled, multicenter study. Ostomy WoundManage 2005;51:24e39.

5. RobsonMC,EdstromLE.Thediabetic foot: analternativeapproachto major amputation. Surg Clin North Am 1977;57:1089e102.

6. Robson MC, Edstrom LE. Conservative management of theulcerated diabetic foot. Plast Reconstr Surg 1977;59:551e4.

7. Apelqvist J, Bakker K, van Houtum WH, Nabuurs-Franssen MH,Schaper NC. International consensus and practical guidelineson the management and the prevention of the diabetic foot.Diabetes Metab Res Rev 2000;16:S84e92.

8. Crawford F, Inkster M, Kleijnen J, Fahey T. Predicting footulcers in patients with diabetes: a systematic review and meta-analysis. QJ Med 2007;100:65e86.

9. Stavosky J, Stuck R, Vanore J. Diabetic foot disorders: a clinicalpractice guideline. J Foot Ankle Surg 2000;39:S1e60.

10. Sheahan MG, Hamdan AD, Veraldi JR, McArthur CS, Skillman JJ,Campbell DR. Lower extremity minor amputations: the roles ofdiabetes mellitus and timing of revascularization. J Vasc Surg2005;42:476e80.

11. Faglia E, Mantero M, Caminiti M. Extensive use of peripheralangioplasty, particularly infrapopliteal, in the treatment ofischemic diabetic foot ulcers: clinical results of a multicentricstudy of 221 consecutive diabetic subjects. J Intern Med 2002;252:225e32.

12. Pomposelli Jr FB, Kansal N, Hamdan AD. A decade ofexperience with dorsalis pedis artery bypass: analysis ofoutcome in more than 1000 cases. J Vasc Surg 2003;37:307e15.

13. Tannenbaum GA, Pomposelli Jr FB, Marcaccio EJ. Safety of veinbypass grafting to the dorsal pedal artery in diabetic patientswith foot infections. J Vasc Surg 1992;15:982e8.

14. Sakai S, Terayama I. Modification of island subcutaneouspedicle flap for the reconstruction of defects of the sole of thefoot. Br J Plast Surg 1991;44:179e82.

15. Hidalgo DA, Shaw WW. Anatomic basis of plantar flap design.Plast Reconstr Surg 1986;78:627e36.

16. Mathes SJ, Nahai F. Classification of the vascular anatomy ofmuscles: experimental and clinical correlation. Plast ReconstrSurg 1981;67:177e87.

17. Serletti JM, Deuber MA, Guidera PM. Atherosclerosis of thelower-extremity and free-tissue reconstruction for limbsalvage. Plast Reconstr Surg 1995;96:1136e44.

18. Wagner FW. The dysvascular foot: a system of diagnosis andtreatment. Foot Ankle 1981;2:64e122.

19. Lavery LA, Armstrong DG, Harkless LB. Classification of dia-betic foot wounds. J Foot Ankle Surg 1996;35:528e31.

20. Wheelock Jr FC. Transmetatarsal amputations and arterialsurgery in diabetic patients. N Engl J Med 1961;16:316e20.

21. Johannesson A, Larsson GU, Ramstrand N, Turkiewicz A,Wirehn AB, Atroshi I. Incidence of low-limb amputation in thediabetic and nondiabetic general population. Diabetic Care2009;32:275e80.

22. Oyibo SO, June EB, Tarawneh I, Nguyen HC, Harkless LB,Boulton AJM. A comparison of two diabetic foot ulcer classifi-cation systems. Diabetic Care 2001;24:84e8.

23. Fife CE, Smart DR, Sheffield PJ, Hopf HW, Hawkins G, Clarke D.Transcutaneous oximetry in clinical practice: consensusstatements from an expert panel based on evidence. UnderseaHyperb Med 2009;36:43e53.

24. Edwards J, Stapley S. Debridement of diabetic foot ulcers.Cochrane Database Syst Rev 2010;20. CD003556.

25. Smith J. Debridement of diabetic foot ulcers. Cochrane Data-base Syst Rev 2002;4. CD003556.

26. Gregor S, Maegele M, Sauerland S, Krahn JF, Peinemann F,Lange S. Negative pressure wound therapy: a vacuum ofevidence? Arch Surg 2008;143:189e96.