Hindawi Publishing CorporationInternational Journal of Vascular MedicineVolume 2013 Article ID 296169 7 pageshttpdxdoiorg1011552013296169
Clinical StudyDiabetic Foot Surgical Approach in Emergency
C Setacci1 P Sirignano1 G Mazzitelli1 F Setacci1 G Messina2
G Galzerano1 and G de Donato1
1 Vascular and Endovascular Surgery Unit Department of Medicine Surgery and Neurological SciencesUniversity of Siena Viale Bracci 1 53100 Siena Italy
2 Area of Public Health Department of Molecular and Developmental Medicine University of Siena Siena Italy
Correspondence should be addressed to C Setacci setacciunisiit
Received 13 June 2013 Accepted 10 September 2013
Academic Editor Umberto Marcello Bracale
Copyright copy 2013 C Setacci et alThis is an open access article distributed under theCreativeCommonsAttribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Introduction Critical limb lschemia (CLI) and particularly diabetic foot (DF) are still considered ldquoCinderellardquo in our departmentsAnyway the presence of arterial obstructive disease increases the risk of amputation by itself when it is associated with footinfection the risk of amputation is greatly increasedMethods From January 2007 to December 2011 375 patients with DF infectionand CLI have been admitted to our Unit from 2007 to 2009 192 patients (Group A) underwent surgical debridement of the lesionfollowed by a delayed revascularization from 2010 to 2011 183 patients (Group B) were treated following a new 4-step protocol (1)early diagnosis with a 24 h on call DF team (2) urgent treatment of severe foot infectionwith an aggressive surgical debridement (3)early revascularization within 24 hours (4) definitive treatment wound healing reconstructive surgery and orthesis We reportedrates of mortality major amputation and foot healing at 6months of followup ResultsThemajority of patients in both groups weremale no statistical differences in medical history and clinical condition were reported at the baselineThemain difference betweenthe two groups was the mean time from debridement to revascularization (3 days in Group A and 24 hours in Group B) After 6months of follow-up mortality was 11 in Group A versus 44 in Group BMajor amputation rate was 396 and 246 in GroupsA and B respectively Wound healing was achieved in 178 in Group A and 208 in Group B Conclusions This protocol requiresa lot of professional skills that should to reach the goal to avoid major amputations in patients with DF Only an interdisciplinaryintegrated DF team and an early intervention may significantly impact the outcome of our patients ldquoTime is Tissuerdquo
1 Introduction
Diabetes is a chronic disease that approximately involves 350million people (65) worldwide with an increasing trend tosome 440 million (78) by 2030 [1] It is burdened by micro-angiopathic (nephropathy retinopathy and neuropathy) andmacroangiopathic complications (cardiovascular disease andfatal or nonfatal stroke)
Cardiovascular diseases are the leading cause of morbid-ity andmortality in diabetes mellitus especially in type II [2]Overall myocardial infarction fatal or nonfatal stroke andamputations are 2 to 4 times more frequent and globalcardiovascular risk is about 3 times higher in diabetic patientsthan in the nondiabetic population [3]
By the way in a Finnish study mortality in patients withtype II diabetes without prior myocardial infarction turned
out to be even equal to that of nondiabetic subjects with priormyocardial infarction [4]
Peripheral arterial disease (PAD) represents a continuumof disease entities that range between asymptomatic PADstable symptomatic intermittent claudication CLI acute limbischemia and amputation CLI is defined as PAD causingresting lower-extremity pain at rest and having threatenedor frank tissue loss and is classified as Rutherford-BeckerClasses 4ndash6 or Fontaine Classes III and IV CLI is a disablingdisease and represents the end of the spectrum of PAD priorto tissue and limb loss Other definitions for CLI have beensuggested to include absolute pressures of ankle pressurelt50ndash70mmHg toe pressure lt30ndash50mmHg or reducedTCPO
2lt30ndash50mmHg
Diabetic foot (DF) is one of the main complications ofdiabetes mellitus it involves approximately 15 of diabetic
2 International Journal of Vascular Medicine
patients [5 6] and represents the main cause of amputationin developed countries [7ndash9] DF is a multifactorial diseasesince neuropathy peripheral vasculopathy and a lower resis-tance to infections contribute to its development [10]
Feet complications closely related to neuropathy andobstructive peripheral vascular disease are responsible formore than 1 million leg amputations every year [11]
The presence of foot infections could dramatically im-prove the risk of amputation Frequently DF complicates theclinical course of ulcerative lesions of the foot and also greatlyincreases the risk of amputation especially when associatedwith a severe deficiency of blood tissue perfusion [12]
The treatment of DF ulcers significantly depends on thevascularization and the presence of infectious process
Treating an infected lesion without having secured anappropriate vascular support does not make sense The footneeds greater vascular support to heal than what is needednot to get sick
Anyway the presence of arterial obstructive diseaseincreases the risk of amputation by itself when it is associatedwith foot infection which frequently complicates the clinicalcourse of DF the risk of amputation is greatly increased [13ndash15]
A main issue is who and when to treat a patient with DFNo consensus is reported in the literature about health-careprofessionals involved in these fields and about the timing ofthe treatments
The aim of this work is to analyse whether the intro-duction of a new multidisciplinary protocol might changethe outcome of our patients in terms of mortality morbiditymajor amputation and wounds healing
2 Materials and Methods
From January 2007 to December 2011 375 patients withDF infections and CLI have been admitted to our center ofVascular and Endovascular Surgery
The treatment of these patients has always been char-acterized by interdisciplinarity with implication of variousprofessionals in the several stages of the long process ofhealing
Since January 2010 our center adopted a new-shared pro-tocol that was applied to all treated patients
The protocol is divided into four phases and provides thefollowing
(1) early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) urgent treatment of severe foot infection with anaggressive surgical debridement
(3) early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) definitive treatment wound healing reconstructivesurgery and orthesis
On the basis of these protocols we divided our expe-riences into two different phases from 2007 to 2009 192patients (Group A) underwent surgical debridement of thelesion followed by a delayed revascularization from 2010 to2011 183 patients (Group B) were treated following thedescribed protocol Demographic clinical and intraoper-ative variables were entered into a specific database bythe operating team Data were collected in a computeriseddatabase and were analysed prospectively
21 Surgical Treatment All patients underwent clinicalexamination ABI (ankle-brachial index) measurement andultrasound examination before treatment The angiographywas performed at the same time as the procedure in order tomap the femoropopliteal lesions accurately and thus optimizethe revascularization strategy All patients were treated bya vascular surgeon in an operating theatre equipped with aportable fluoroscopy unit (GE-OEC 9800 GE Medical Sys-tems Salt Lake City UT USA)
In our center anterograde ipsilateral percutaneousfemoral access was preferred when at least 5 cm of a patentproximal segment of superficial femoral artery (SFA) wasevident at ultrasonography A contralateral approach viaa cross-over long sheath was only used in the presence ofeither SFA occlusion in its origin high femoral bifurcation(documented by ultrasound) or obesity We were able tocheck the correct localisation of the common femoral arterypuncture and reduce the risk of retroperitoneal bleedingusing micropuncture sets and contrast injections underfluoroscopy
A soft angled hydrophilic 003510158401015840 guidewire in combina-tion with a 5-F angled hydrophilic catheter was brought nearthe origin of the occlusion
Advancing the guidewire through the true lumen wasattempted in all cases When needed the subintimal planewas entered by forming a loop at the end of the guidewireand advancing it along with the catheter across the occludedarterial segment A reentry device was used (Outback CordisCorporation Miami Lakes FL USA in all cases) only whenrecanalisation by simple subintimal angioplasty (SAP) wasunsuccessful Following confirmation of catheter reentryinto the true lumen balloon angioplasty was used to dilatethe subintimal channel Stenting was performed only whenresidual stenosis was gt30 or there was a flow-limiting dis-section
We tried to use a standardised approach a brief SAPprocedure of 30ndash40min and use of a reentry device areadvised when accessing the true lumen proves difficult soas not to dissect the popliteal artery or threaten the supra-genicular collaterals If the procedure cannot be concludedsafely we continued the intervention surgically or used ahybrid approach The presence of a vascular surgeon in theteam is important as in the case of a failed SAP the firstintervention should not preclude the possibility of furthersurgical revascularization [16]
Our surgical or endovascular approach is oriented torespect the angiosome concept due to the necessity of a directblood flow to the wound related arteries [17]
International Journal of Vascular Medicine 3
Table 1 Demographic characteristics of the two study groups
Group A Group BMean age 756 767Male 817 786Coronary artery disease 63 644COPD 359 387Renal failure 578 584Hypertension 885 918Dyslipidemia 755 786
22 Statistical Analysis The Kaplan Meier method was usedto show the trend in the two groups The log rank test wasused in order to detect if therewere any statistically significantdifferences between the two curves Significance level was set(119875 lt 005) Stata SE version 121 StataCorp College StationTexas USA software was used for the analysis
We report mortality rate major amputation rate (definedas above the ankle amputation) and wound healing rate inboth groups at 6 months of followup Minor amputationbelow the ankle was considered as a wound healing whenfunction of the limbs was conserved and as nonhealing ulcerin other cases
Limb function in below the ankle amputation was con-served by the use of appropriate orthesis that ensures thedischarge of the affected area in the early postoperativeperiod These devices allow achieving a weight bearing ofthe affected area from amputation (whether calcaneal tarsalor metatarsal) by sole rocking After successful healing it ispossible to prescribe custom-made shoes with rigid filling toensure proper mobility
3 Results
The majority of patients were male in both groups Nosignificant differences in terms of age or comorbidities wererecorded in the present seriesDemographic characteristics ofpatients in both groups are described in Table 1 All patientswere treated in urgent or emergent settings
The main time between debridement and revasculariza-tion was 3 days (range 1ndash7 days) in Group A all patients inGroup B were revascularized within 24 h from the surgicaldebridement In our experience even in very complex casesa primary amputation was never performed
As described above all patients underwent first stageendovascular procedure Only in case of endovascular fail-ure an intraoperative surgical conversion was performedEndovascular revascularization was successfully performedin 847 of the patients Stenting was performed only in abail-out situation Open surgical conversion was performedintraoperatively in all cases of failure in endovascular recanal-ization
In all cases the patients executed a specific antibiotictherapy based on a previously performed antibiogram
At six months of followup we report 22 (11) deaths inGroup A and 9 (44) deaths in Group B which represents
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 1 KM estimates survival rates
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 2 KM estimates amputation rates
a statistically significant difference between the two groups(119875 = 00224 and HR = 041) (Figure 1)
In Group A we reported 2 deaths (104) due to septicshock both patients were septic at moment of clinical pre-sentation An endovascular recanalization with restorationof direct flow to the foot was achieved in both casesUnfortunately both patients developed an acute renal failureand a multiorgan failure
During the followups 12 cases of fatal MIs were observed(625) 5 fatal strokes (260) and 3 renal failures (156)
No case of septic shock was recorded in Group B FatalMI was observed in 6 patients during the followup (327)stroke in 2 patients (109) and 1 patient (054) death ofcolon cancer at 3 months of followup
Major amputation rate was respectively 396 and 246in Group A and in Group B (119875 = 00024 HR = 058)(Figure 2) During the follow-up period all patients in bothgroups were continuously treated and assisted by vascularsurgeons vascular nurses and all the other care-providersinvolved in the healing process by clinical evaluation andwound care Wound healing (Figure 3) was achieved in 34patients (178) in Group A and in 39 patients (208) inGroup B (119875 = 045 HR 118) (Figure 4)
4 International Journal of Vascular Medicine
(a) (b) (c)
Figure 3 Preoperative (a) intraoperative (b) and follow-up images (c) of DF ulcers
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 4 KM estimates wound healing rates
4 Discussion
Critical limb ischemia and in particular DF are still consid-ered ldquoCinderellasrdquo in our departments And this is difficult toexplain if we consider that every year more than one millionpeople suffer from a lower limb amputation as a result ofdiabetes It is hard to believe that although 85 of allamputations are preceded by the development of foot ulcersthe prevalence of amputations ranges oscillates from 02 upto 48 [18]
We must consider that the complications associated withthe diabetic disease are difficult to manage and require asignificant commitment in terms of health care [19 20]
Prompers et al reported that the presence of criticallimb ischemia greatly increases the risk of major amputationOf note in their experience the presence of diabetic neu-rophathy (even motor or sensory) is linked only to a higher
incidence of ulceration no major risk of amputation wasdetected [21]
Ulcers depending on pathogenetical features can bedefined as neuropathic ischemic or neuroischemic all ofthem can be complicate by a superinfection [22]
Even if many different staging systems of ulcerativelesions have been defined in recent years theWagnerrsquos classi-fication continues to be the most widely accepted
Wagnerrsquos classification identifies six categories of lesionsprogressively worsening from stage 0 to stage 5 depending oninvolvement of different tissuersquos layers topographic locationand presence of any infection [23] This classification allowsa clinical diagnosis of the lesion but on the other side itdoes not consider the local vascular conditions This is themain limit because ischemia is the main factor conditioningthe clinical evolution of lesions and also the choice betweendifferent kinds of treatments [24] In order to obviate thisproblem a new classification the Texas Wound Classifica-tion which considers also the possible presence of ischemiahas been validated
The Texas Wound Classification demonstrated a positivecorrelation between dimensions of ulcer ischemia and infec-tion with the increase of relative risk of amputation (Table 2)Moreover it demonstrated a significant positive relationshipbetween the extension and the depth of the infection andthe risk of amputation [25] Early control of infective processrepresents the main therapeutic goal of emergency surgery ininfected DFThe general impression although not supportedby specific prospective studies is that patients with rest painand trophic lesions have a worse prognosis than those withonly pain and that the greater size of the ulcer worsens theprognosis but only with respect to limb salvage and not forthe purpose of patients survival [26]
Diabetes is themost important risk factor for critical limbischemia [19 27ndash30] and it is well recognized that diabetic
International Journal of Vascular Medicine 5
Table 2 Texas Wound Classification
Stage Grade0 I II III
A(no infectionor ischemia)
Pre- or postulcerativelesion completelyepithelialized
Superficial wound notinvolving tendoncapsule or bone
Wound penetrating totendon or capsule
Wound penetrating tobone or joint
B Infection Infection Infection InfectionC Ischemia Ischemia Ischemia Ischemia
D Infection andischemia
Infection andischemia
Infection andischemia
Infection andischemia
patients have a high risk rate of both amputation and deathcompared with nondiabetics [31]
Despite the benefits of pharmacologic therapy arterialrevascularization remains a mainstay in the management ofCLI because the restoration of adequate blood flow to the footis crucial to provide pain relief promote wound healing andavoid amputation Although surgical revascularization is animportant therapeutic option recent data supports the use ofpercutaneous transluminal angioplasty which is both feasibleand safe in this setting [32ndash35] However recent reports fromthe literature seem to suggest the positive role of newcommercially available drugs in order to prevent ulceration indiabetic patientsThese findingsmight completely change thescenario in the future [36]
More aggressive techniques have been developed toimprove the results of percutaneous transluminal angioplastyin vessels below the knee Techniques such as subintimalangioplasty [37] retrograde approach with transpedal access[38] subintimal arterial flossing with antegrade-retrogradeintervention [39 40] transcollateral angioplasty [41] andpedal-plantar loop [42 43] are improving the success ratesof percutaneous transluminal angioplasty even in the mostdistal vascular territories
By theway control of any local sepsis through appropriateuse of surgical (debridement drainage and even amputation)and medical (antibiotics) modalities is always the immediatepriority in DF management [44]
Consequently timing has a key role for the diabeticrsquos foottreatment especially if it is infected
Faglia et al [45] have confirmed how in case of CLI(especially if it is associated with a severe infection) an earlysurgical treatment of the infection followed by early revas-cularization procedure can achieve limb salvage or a moredistal level of foot amputation Caravaggi [11] has proposedan ldquoIntegrated Surgical Approachrdquo that considers the mainaspects of treatment of severe foot infection time emergencysurgical treatment and revascularization procedures Sinceearly surgical treatment of infection is closely correlated withlimb salvage they have underlined that surgical debridementhas to be performed as soon as possible regardless of vascularcondition of the foot Revascularization procedures bothsurgical or endovascular are secondary in comparison to thelocal and systemic infections control
In conclusion the need for a coordinate multidisci-plinary care has long been obviousThe recent growth of ded-icated amputation prevention centers represents a positive
trend and new drugs could modify the natural history of thedisease
At the moment we would like to suggest a four-stepapproach to patients with DF
(1) Early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) Urgent treatment of severe foot infection with anaggressive surgical debridement
(3) Early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) Definitive treatment wound healing reconstructivesurgery and orthesis
This solution is also recommended by the most recentguidelines in particular by International Guidelines on thetreatment of diabetic foot and the Guidelines of the EuropeanSociety of Vascular and Endovascular Surgery of critical limbischemia and diabetic foot [46]
In our experience many different professional skillsshould work together 24 hndash365 d to reach the goal to avoidmajor amputations in patients with DF It is a hard andcomplex work but it is proven that only an interdisciplinaryintegrated diabetic foot Teammay lead to a significant impacton the outcome of our patients ldquoTime is Tissuerdquo
References
[1] World Health Organisation Fact sheet no 312 2011[2] L O Watkins ldquoEpidemiology and burden of cardiovascular
diseaserdquo Clinical Cardiology vol 27 no 6 pp III2ndashIII6 2004[3] J Stamler O Vaccaro J D Neaton and D Wentworth
ldquoDiabetes other risk factors and 12-yr cardiovascular mortalityfor men screened in the multiple risk factor intervention trialrdquoDiabetes Care vol 16 no 2 pp 434ndash444 1993
[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjects withtype 2 diabetes and in nondiabetic subjects with and withoutprior myocardial infarctionrdquo New England Journal of Medicinevol 339 no 4 pp 229ndash234 1998
[5] American Diabetes Association ldquoDiabetes 1993 Vital StatisticsrdquoADA publication no PMDIVS93 1993
6 International Journal of Vascular Medicine
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
patients [5 6] and represents the main cause of amputationin developed countries [7ndash9] DF is a multifactorial diseasesince neuropathy peripheral vasculopathy and a lower resis-tance to infections contribute to its development [10]
Feet complications closely related to neuropathy andobstructive peripheral vascular disease are responsible formore than 1 million leg amputations every year [11]
The presence of foot infections could dramatically im-prove the risk of amputation Frequently DF complicates theclinical course of ulcerative lesions of the foot and also greatlyincreases the risk of amputation especially when associatedwith a severe deficiency of blood tissue perfusion [12]
The treatment of DF ulcers significantly depends on thevascularization and the presence of infectious process
Treating an infected lesion without having secured anappropriate vascular support does not make sense The footneeds greater vascular support to heal than what is needednot to get sick
Anyway the presence of arterial obstructive diseaseincreases the risk of amputation by itself when it is associatedwith foot infection which frequently complicates the clinicalcourse of DF the risk of amputation is greatly increased [13ndash15]
A main issue is who and when to treat a patient with DFNo consensus is reported in the literature about health-careprofessionals involved in these fields and about the timing ofthe treatments
The aim of this work is to analyse whether the intro-duction of a new multidisciplinary protocol might changethe outcome of our patients in terms of mortality morbiditymajor amputation and wounds healing
2 Materials and Methods
From January 2007 to December 2011 375 patients withDF infections and CLI have been admitted to our center ofVascular and Endovascular Surgery
The treatment of these patients has always been char-acterized by interdisciplinarity with implication of variousprofessionals in the several stages of the long process ofhealing
Since January 2010 our center adopted a new-shared pro-tocol that was applied to all treated patients
The protocol is divided into four phases and provides thefollowing
(1) early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) urgent treatment of severe foot infection with anaggressive surgical debridement
(3) early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) definitive treatment wound healing reconstructivesurgery and orthesis
On the basis of these protocols we divided our expe-riences into two different phases from 2007 to 2009 192patients (Group A) underwent surgical debridement of thelesion followed by a delayed revascularization from 2010 to2011 183 patients (Group B) were treated following thedescribed protocol Demographic clinical and intraoper-ative variables were entered into a specific database bythe operating team Data were collected in a computeriseddatabase and were analysed prospectively
21 Surgical Treatment All patients underwent clinicalexamination ABI (ankle-brachial index) measurement andultrasound examination before treatment The angiographywas performed at the same time as the procedure in order tomap the femoropopliteal lesions accurately and thus optimizethe revascularization strategy All patients were treated bya vascular surgeon in an operating theatre equipped with aportable fluoroscopy unit (GE-OEC 9800 GE Medical Sys-tems Salt Lake City UT USA)
In our center anterograde ipsilateral percutaneousfemoral access was preferred when at least 5 cm of a patentproximal segment of superficial femoral artery (SFA) wasevident at ultrasonography A contralateral approach viaa cross-over long sheath was only used in the presence ofeither SFA occlusion in its origin high femoral bifurcation(documented by ultrasound) or obesity We were able tocheck the correct localisation of the common femoral arterypuncture and reduce the risk of retroperitoneal bleedingusing micropuncture sets and contrast injections underfluoroscopy
A soft angled hydrophilic 003510158401015840 guidewire in combina-tion with a 5-F angled hydrophilic catheter was brought nearthe origin of the occlusion
Advancing the guidewire through the true lumen wasattempted in all cases When needed the subintimal planewas entered by forming a loop at the end of the guidewireand advancing it along with the catheter across the occludedarterial segment A reentry device was used (Outback CordisCorporation Miami Lakes FL USA in all cases) only whenrecanalisation by simple subintimal angioplasty (SAP) wasunsuccessful Following confirmation of catheter reentryinto the true lumen balloon angioplasty was used to dilatethe subintimal channel Stenting was performed only whenresidual stenosis was gt30 or there was a flow-limiting dis-section
We tried to use a standardised approach a brief SAPprocedure of 30ndash40min and use of a reentry device areadvised when accessing the true lumen proves difficult soas not to dissect the popliteal artery or threaten the supra-genicular collaterals If the procedure cannot be concludedsafely we continued the intervention surgically or used ahybrid approach The presence of a vascular surgeon in theteam is important as in the case of a failed SAP the firstintervention should not preclude the possibility of furthersurgical revascularization [16]
Our surgical or endovascular approach is oriented torespect the angiosome concept due to the necessity of a directblood flow to the wound related arteries [17]
International Journal of Vascular Medicine 3
Table 1 Demographic characteristics of the two study groups
Group A Group BMean age 756 767Male 817 786Coronary artery disease 63 644COPD 359 387Renal failure 578 584Hypertension 885 918Dyslipidemia 755 786
22 Statistical Analysis The Kaplan Meier method was usedto show the trend in the two groups The log rank test wasused in order to detect if therewere any statistically significantdifferences between the two curves Significance level was set(119875 lt 005) Stata SE version 121 StataCorp College StationTexas USA software was used for the analysis
We report mortality rate major amputation rate (definedas above the ankle amputation) and wound healing rate inboth groups at 6 months of followup Minor amputationbelow the ankle was considered as a wound healing whenfunction of the limbs was conserved and as nonhealing ulcerin other cases
Limb function in below the ankle amputation was con-served by the use of appropriate orthesis that ensures thedischarge of the affected area in the early postoperativeperiod These devices allow achieving a weight bearing ofthe affected area from amputation (whether calcaneal tarsalor metatarsal) by sole rocking After successful healing it ispossible to prescribe custom-made shoes with rigid filling toensure proper mobility
3 Results
The majority of patients were male in both groups Nosignificant differences in terms of age or comorbidities wererecorded in the present seriesDemographic characteristics ofpatients in both groups are described in Table 1 All patientswere treated in urgent or emergent settings
The main time between debridement and revasculariza-tion was 3 days (range 1ndash7 days) in Group A all patients inGroup B were revascularized within 24 h from the surgicaldebridement In our experience even in very complex casesa primary amputation was never performed
As described above all patients underwent first stageendovascular procedure Only in case of endovascular fail-ure an intraoperative surgical conversion was performedEndovascular revascularization was successfully performedin 847 of the patients Stenting was performed only in abail-out situation Open surgical conversion was performedintraoperatively in all cases of failure in endovascular recanal-ization
In all cases the patients executed a specific antibiotictherapy based on a previously performed antibiogram
At six months of followup we report 22 (11) deaths inGroup A and 9 (44) deaths in Group B which represents
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 1 KM estimates survival rates
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 2 KM estimates amputation rates
a statistically significant difference between the two groups(119875 = 00224 and HR = 041) (Figure 1)
In Group A we reported 2 deaths (104) due to septicshock both patients were septic at moment of clinical pre-sentation An endovascular recanalization with restorationof direct flow to the foot was achieved in both casesUnfortunately both patients developed an acute renal failureand a multiorgan failure
During the followups 12 cases of fatal MIs were observed(625) 5 fatal strokes (260) and 3 renal failures (156)
No case of septic shock was recorded in Group B FatalMI was observed in 6 patients during the followup (327)stroke in 2 patients (109) and 1 patient (054) death ofcolon cancer at 3 months of followup
Major amputation rate was respectively 396 and 246in Group A and in Group B (119875 = 00024 HR = 058)(Figure 2) During the follow-up period all patients in bothgroups were continuously treated and assisted by vascularsurgeons vascular nurses and all the other care-providersinvolved in the healing process by clinical evaluation andwound care Wound healing (Figure 3) was achieved in 34patients (178) in Group A and in 39 patients (208) inGroup B (119875 = 045 HR 118) (Figure 4)
4 International Journal of Vascular Medicine
(a) (b) (c)
Figure 3 Preoperative (a) intraoperative (b) and follow-up images (c) of DF ulcers
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 4 KM estimates wound healing rates
4 Discussion
Critical limb ischemia and in particular DF are still consid-ered ldquoCinderellasrdquo in our departments And this is difficult toexplain if we consider that every year more than one millionpeople suffer from a lower limb amputation as a result ofdiabetes It is hard to believe that although 85 of allamputations are preceded by the development of foot ulcersthe prevalence of amputations ranges oscillates from 02 upto 48 [18]
We must consider that the complications associated withthe diabetic disease are difficult to manage and require asignificant commitment in terms of health care [19 20]
Prompers et al reported that the presence of criticallimb ischemia greatly increases the risk of major amputationOf note in their experience the presence of diabetic neu-rophathy (even motor or sensory) is linked only to a higher
incidence of ulceration no major risk of amputation wasdetected [21]
Ulcers depending on pathogenetical features can bedefined as neuropathic ischemic or neuroischemic all ofthem can be complicate by a superinfection [22]
Even if many different staging systems of ulcerativelesions have been defined in recent years theWagnerrsquos classi-fication continues to be the most widely accepted
Wagnerrsquos classification identifies six categories of lesionsprogressively worsening from stage 0 to stage 5 depending oninvolvement of different tissuersquos layers topographic locationand presence of any infection [23] This classification allowsa clinical diagnosis of the lesion but on the other side itdoes not consider the local vascular conditions This is themain limit because ischemia is the main factor conditioningthe clinical evolution of lesions and also the choice betweendifferent kinds of treatments [24] In order to obviate thisproblem a new classification the Texas Wound Classifica-tion which considers also the possible presence of ischemiahas been validated
The Texas Wound Classification demonstrated a positivecorrelation between dimensions of ulcer ischemia and infec-tion with the increase of relative risk of amputation (Table 2)Moreover it demonstrated a significant positive relationshipbetween the extension and the depth of the infection andthe risk of amputation [25] Early control of infective processrepresents the main therapeutic goal of emergency surgery ininfected DFThe general impression although not supportedby specific prospective studies is that patients with rest painand trophic lesions have a worse prognosis than those withonly pain and that the greater size of the ulcer worsens theprognosis but only with respect to limb salvage and not forthe purpose of patients survival [26]
Diabetes is themost important risk factor for critical limbischemia [19 27ndash30] and it is well recognized that diabetic
International Journal of Vascular Medicine 5
Table 2 Texas Wound Classification
Stage Grade0 I II III
A(no infectionor ischemia)
Pre- or postulcerativelesion completelyepithelialized
Superficial wound notinvolving tendoncapsule or bone
Wound penetrating totendon or capsule
Wound penetrating tobone or joint
B Infection Infection Infection InfectionC Ischemia Ischemia Ischemia Ischemia
D Infection andischemia
Infection andischemia
Infection andischemia
Infection andischemia
patients have a high risk rate of both amputation and deathcompared with nondiabetics [31]
Despite the benefits of pharmacologic therapy arterialrevascularization remains a mainstay in the management ofCLI because the restoration of adequate blood flow to the footis crucial to provide pain relief promote wound healing andavoid amputation Although surgical revascularization is animportant therapeutic option recent data supports the use ofpercutaneous transluminal angioplasty which is both feasibleand safe in this setting [32ndash35] However recent reports fromthe literature seem to suggest the positive role of newcommercially available drugs in order to prevent ulceration indiabetic patientsThese findingsmight completely change thescenario in the future [36]
More aggressive techniques have been developed toimprove the results of percutaneous transluminal angioplastyin vessels below the knee Techniques such as subintimalangioplasty [37] retrograde approach with transpedal access[38] subintimal arterial flossing with antegrade-retrogradeintervention [39 40] transcollateral angioplasty [41] andpedal-plantar loop [42 43] are improving the success ratesof percutaneous transluminal angioplasty even in the mostdistal vascular territories
By theway control of any local sepsis through appropriateuse of surgical (debridement drainage and even amputation)and medical (antibiotics) modalities is always the immediatepriority in DF management [44]
Consequently timing has a key role for the diabeticrsquos foottreatment especially if it is infected
Faglia et al [45] have confirmed how in case of CLI(especially if it is associated with a severe infection) an earlysurgical treatment of the infection followed by early revas-cularization procedure can achieve limb salvage or a moredistal level of foot amputation Caravaggi [11] has proposedan ldquoIntegrated Surgical Approachrdquo that considers the mainaspects of treatment of severe foot infection time emergencysurgical treatment and revascularization procedures Sinceearly surgical treatment of infection is closely correlated withlimb salvage they have underlined that surgical debridementhas to be performed as soon as possible regardless of vascularcondition of the foot Revascularization procedures bothsurgical or endovascular are secondary in comparison to thelocal and systemic infections control
In conclusion the need for a coordinate multidisci-plinary care has long been obviousThe recent growth of ded-icated amputation prevention centers represents a positive
trend and new drugs could modify the natural history of thedisease
At the moment we would like to suggest a four-stepapproach to patients with DF
(1) Early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) Urgent treatment of severe foot infection with anaggressive surgical debridement
(3) Early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) Definitive treatment wound healing reconstructivesurgery and orthesis
This solution is also recommended by the most recentguidelines in particular by International Guidelines on thetreatment of diabetic foot and the Guidelines of the EuropeanSociety of Vascular and Endovascular Surgery of critical limbischemia and diabetic foot [46]
In our experience many different professional skillsshould work together 24 hndash365 d to reach the goal to avoidmajor amputations in patients with DF It is a hard andcomplex work but it is proven that only an interdisciplinaryintegrated diabetic foot Teammay lead to a significant impacton the outcome of our patients ldquoTime is Tissuerdquo
References
[1] World Health Organisation Fact sheet no 312 2011[2] L O Watkins ldquoEpidemiology and burden of cardiovascular
diseaserdquo Clinical Cardiology vol 27 no 6 pp III2ndashIII6 2004[3] J Stamler O Vaccaro J D Neaton and D Wentworth
ldquoDiabetes other risk factors and 12-yr cardiovascular mortalityfor men screened in the multiple risk factor intervention trialrdquoDiabetes Care vol 16 no 2 pp 434ndash444 1993
[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjects withtype 2 diabetes and in nondiabetic subjects with and withoutprior myocardial infarctionrdquo New England Journal of Medicinevol 339 no 4 pp 229ndash234 1998
[5] American Diabetes Association ldquoDiabetes 1993 Vital StatisticsrdquoADA publication no PMDIVS93 1993
6 International Journal of Vascular Medicine
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
Table 1 Demographic characteristics of the two study groups
Group A Group BMean age 756 767Male 817 786Coronary artery disease 63 644COPD 359 387Renal failure 578 584Hypertension 885 918Dyslipidemia 755 786
22 Statistical Analysis The Kaplan Meier method was usedto show the trend in the two groups The log rank test wasused in order to detect if therewere any statistically significantdifferences between the two curves Significance level was set(119875 lt 005) Stata SE version 121 StataCorp College StationTexas USA software was used for the analysis
We report mortality rate major amputation rate (definedas above the ankle amputation) and wound healing rate inboth groups at 6 months of followup Minor amputationbelow the ankle was considered as a wound healing whenfunction of the limbs was conserved and as nonhealing ulcerin other cases
Limb function in below the ankle amputation was con-served by the use of appropriate orthesis that ensures thedischarge of the affected area in the early postoperativeperiod These devices allow achieving a weight bearing ofthe affected area from amputation (whether calcaneal tarsalor metatarsal) by sole rocking After successful healing it ispossible to prescribe custom-made shoes with rigid filling toensure proper mobility
3 Results
The majority of patients were male in both groups Nosignificant differences in terms of age or comorbidities wererecorded in the present seriesDemographic characteristics ofpatients in both groups are described in Table 1 All patientswere treated in urgent or emergent settings
The main time between debridement and revasculariza-tion was 3 days (range 1ndash7 days) in Group A all patients inGroup B were revascularized within 24 h from the surgicaldebridement In our experience even in very complex casesa primary amputation was never performed
As described above all patients underwent first stageendovascular procedure Only in case of endovascular fail-ure an intraoperative surgical conversion was performedEndovascular revascularization was successfully performedin 847 of the patients Stenting was performed only in abail-out situation Open surgical conversion was performedintraoperatively in all cases of failure in endovascular recanal-ization
In all cases the patients executed a specific antibiotictherapy based on a previously performed antibiogram
At six months of followup we report 22 (11) deaths inGroup A and 9 (44) deaths in Group B which represents
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 1 KM estimates survival rates
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 2 KM estimates amputation rates
a statistically significant difference between the two groups(119875 = 00224 and HR = 041) (Figure 1)
In Group A we reported 2 deaths (104) due to septicshock both patients were septic at moment of clinical pre-sentation An endovascular recanalization with restorationof direct flow to the foot was achieved in both casesUnfortunately both patients developed an acute renal failureand a multiorgan failure
During the followups 12 cases of fatal MIs were observed(625) 5 fatal strokes (260) and 3 renal failures (156)
No case of septic shock was recorded in Group B FatalMI was observed in 6 patients during the followup (327)stroke in 2 patients (109) and 1 patient (054) death ofcolon cancer at 3 months of followup
Major amputation rate was respectively 396 and 246in Group A and in Group B (119875 = 00024 HR = 058)(Figure 2) During the follow-up period all patients in bothgroups were continuously treated and assisted by vascularsurgeons vascular nurses and all the other care-providersinvolved in the healing process by clinical evaluation andwound care Wound healing (Figure 3) was achieved in 34patients (178) in Group A and in 39 patients (208) inGroup B (119875 = 045 HR 118) (Figure 4)
4 International Journal of Vascular Medicine
(a) (b) (c)
Figure 3 Preoperative (a) intraoperative (b) and follow-up images (c) of DF ulcers
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 4 KM estimates wound healing rates
4 Discussion
Critical limb ischemia and in particular DF are still consid-ered ldquoCinderellasrdquo in our departments And this is difficult toexplain if we consider that every year more than one millionpeople suffer from a lower limb amputation as a result ofdiabetes It is hard to believe that although 85 of allamputations are preceded by the development of foot ulcersthe prevalence of amputations ranges oscillates from 02 upto 48 [18]
We must consider that the complications associated withthe diabetic disease are difficult to manage and require asignificant commitment in terms of health care [19 20]
Prompers et al reported that the presence of criticallimb ischemia greatly increases the risk of major amputationOf note in their experience the presence of diabetic neu-rophathy (even motor or sensory) is linked only to a higher
incidence of ulceration no major risk of amputation wasdetected [21]
Ulcers depending on pathogenetical features can bedefined as neuropathic ischemic or neuroischemic all ofthem can be complicate by a superinfection [22]
Even if many different staging systems of ulcerativelesions have been defined in recent years theWagnerrsquos classi-fication continues to be the most widely accepted
Wagnerrsquos classification identifies six categories of lesionsprogressively worsening from stage 0 to stage 5 depending oninvolvement of different tissuersquos layers topographic locationand presence of any infection [23] This classification allowsa clinical diagnosis of the lesion but on the other side itdoes not consider the local vascular conditions This is themain limit because ischemia is the main factor conditioningthe clinical evolution of lesions and also the choice betweendifferent kinds of treatments [24] In order to obviate thisproblem a new classification the Texas Wound Classifica-tion which considers also the possible presence of ischemiahas been validated
The Texas Wound Classification demonstrated a positivecorrelation between dimensions of ulcer ischemia and infec-tion with the increase of relative risk of amputation (Table 2)Moreover it demonstrated a significant positive relationshipbetween the extension and the depth of the infection andthe risk of amputation [25] Early control of infective processrepresents the main therapeutic goal of emergency surgery ininfected DFThe general impression although not supportedby specific prospective studies is that patients with rest painand trophic lesions have a worse prognosis than those withonly pain and that the greater size of the ulcer worsens theprognosis but only with respect to limb salvage and not forthe purpose of patients survival [26]
Diabetes is themost important risk factor for critical limbischemia [19 27ndash30] and it is well recognized that diabetic
International Journal of Vascular Medicine 5
Table 2 Texas Wound Classification
Stage Grade0 I II III
A(no infectionor ischemia)
Pre- or postulcerativelesion completelyepithelialized
Superficial wound notinvolving tendoncapsule or bone
Wound penetrating totendon or capsule
Wound penetrating tobone or joint
B Infection Infection Infection InfectionC Ischemia Ischemia Ischemia Ischemia
D Infection andischemia
Infection andischemia
Infection andischemia
Infection andischemia
patients have a high risk rate of both amputation and deathcompared with nondiabetics [31]
Despite the benefits of pharmacologic therapy arterialrevascularization remains a mainstay in the management ofCLI because the restoration of adequate blood flow to the footis crucial to provide pain relief promote wound healing andavoid amputation Although surgical revascularization is animportant therapeutic option recent data supports the use ofpercutaneous transluminal angioplasty which is both feasibleand safe in this setting [32ndash35] However recent reports fromthe literature seem to suggest the positive role of newcommercially available drugs in order to prevent ulceration indiabetic patientsThese findingsmight completely change thescenario in the future [36]
More aggressive techniques have been developed toimprove the results of percutaneous transluminal angioplastyin vessels below the knee Techniques such as subintimalangioplasty [37] retrograde approach with transpedal access[38] subintimal arterial flossing with antegrade-retrogradeintervention [39 40] transcollateral angioplasty [41] andpedal-plantar loop [42 43] are improving the success ratesof percutaneous transluminal angioplasty even in the mostdistal vascular territories
By theway control of any local sepsis through appropriateuse of surgical (debridement drainage and even amputation)and medical (antibiotics) modalities is always the immediatepriority in DF management [44]
Consequently timing has a key role for the diabeticrsquos foottreatment especially if it is infected
Faglia et al [45] have confirmed how in case of CLI(especially if it is associated with a severe infection) an earlysurgical treatment of the infection followed by early revas-cularization procedure can achieve limb salvage or a moredistal level of foot amputation Caravaggi [11] has proposedan ldquoIntegrated Surgical Approachrdquo that considers the mainaspects of treatment of severe foot infection time emergencysurgical treatment and revascularization procedures Sinceearly surgical treatment of infection is closely correlated withlimb salvage they have underlined that surgical debridementhas to be performed as soon as possible regardless of vascularcondition of the foot Revascularization procedures bothsurgical or endovascular are secondary in comparison to thelocal and systemic infections control
In conclusion the need for a coordinate multidisci-plinary care has long been obviousThe recent growth of ded-icated amputation prevention centers represents a positive
trend and new drugs could modify the natural history of thedisease
At the moment we would like to suggest a four-stepapproach to patients with DF
(1) Early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) Urgent treatment of severe foot infection with anaggressive surgical debridement
(3) Early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) Definitive treatment wound healing reconstructivesurgery and orthesis
This solution is also recommended by the most recentguidelines in particular by International Guidelines on thetreatment of diabetic foot and the Guidelines of the EuropeanSociety of Vascular and Endovascular Surgery of critical limbischemia and diabetic foot [46]
In our experience many different professional skillsshould work together 24 hndash365 d to reach the goal to avoidmajor amputations in patients with DF It is a hard andcomplex work but it is proven that only an interdisciplinaryintegrated diabetic foot Teammay lead to a significant impacton the outcome of our patients ldquoTime is Tissuerdquo
References
[1] World Health Organisation Fact sheet no 312 2011[2] L O Watkins ldquoEpidemiology and burden of cardiovascular
diseaserdquo Clinical Cardiology vol 27 no 6 pp III2ndashIII6 2004[3] J Stamler O Vaccaro J D Neaton and D Wentworth
ldquoDiabetes other risk factors and 12-yr cardiovascular mortalityfor men screened in the multiple risk factor intervention trialrdquoDiabetes Care vol 16 no 2 pp 434ndash444 1993
[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjects withtype 2 diabetes and in nondiabetic subjects with and withoutprior myocardial infarctionrdquo New England Journal of Medicinevol 339 no 4 pp 229ndash234 1998
[5] American Diabetes Association ldquoDiabetes 1993 Vital StatisticsrdquoADA publication no PMDIVS93 1993
6 International Journal of Vascular Medicine
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
Figure 3 Preoperative (a) intraoperative (b) and follow-up images (c) of DF ulcers
100
075
050
025
000
0 2 4 6
Group A
Analysis time
Group B
Figure 4 KM estimates wound healing rates
4 Discussion
Critical limb ischemia and in particular DF are still consid-ered ldquoCinderellasrdquo in our departments And this is difficult toexplain if we consider that every year more than one millionpeople suffer from a lower limb amputation as a result ofdiabetes It is hard to believe that although 85 of allamputations are preceded by the development of foot ulcersthe prevalence of amputations ranges oscillates from 02 upto 48 [18]
We must consider that the complications associated withthe diabetic disease are difficult to manage and require asignificant commitment in terms of health care [19 20]
Prompers et al reported that the presence of criticallimb ischemia greatly increases the risk of major amputationOf note in their experience the presence of diabetic neu-rophathy (even motor or sensory) is linked only to a higher
incidence of ulceration no major risk of amputation wasdetected [21]
Ulcers depending on pathogenetical features can bedefined as neuropathic ischemic or neuroischemic all ofthem can be complicate by a superinfection [22]
Even if many different staging systems of ulcerativelesions have been defined in recent years theWagnerrsquos classi-fication continues to be the most widely accepted
Wagnerrsquos classification identifies six categories of lesionsprogressively worsening from stage 0 to stage 5 depending oninvolvement of different tissuersquos layers topographic locationand presence of any infection [23] This classification allowsa clinical diagnosis of the lesion but on the other side itdoes not consider the local vascular conditions This is themain limit because ischemia is the main factor conditioningthe clinical evolution of lesions and also the choice betweendifferent kinds of treatments [24] In order to obviate thisproblem a new classification the Texas Wound Classifica-tion which considers also the possible presence of ischemiahas been validated
The Texas Wound Classification demonstrated a positivecorrelation between dimensions of ulcer ischemia and infec-tion with the increase of relative risk of amputation (Table 2)Moreover it demonstrated a significant positive relationshipbetween the extension and the depth of the infection andthe risk of amputation [25] Early control of infective processrepresents the main therapeutic goal of emergency surgery ininfected DFThe general impression although not supportedby specific prospective studies is that patients with rest painand trophic lesions have a worse prognosis than those withonly pain and that the greater size of the ulcer worsens theprognosis but only with respect to limb salvage and not forthe purpose of patients survival [26]
Diabetes is themost important risk factor for critical limbischemia [19 27ndash30] and it is well recognized that diabetic
International Journal of Vascular Medicine 5
Table 2 Texas Wound Classification
Stage Grade0 I II III
A(no infectionor ischemia)
Pre- or postulcerativelesion completelyepithelialized
Superficial wound notinvolving tendoncapsule or bone
Wound penetrating totendon or capsule
Wound penetrating tobone or joint
B Infection Infection Infection InfectionC Ischemia Ischemia Ischemia Ischemia
D Infection andischemia
Infection andischemia
Infection andischemia
Infection andischemia
patients have a high risk rate of both amputation and deathcompared with nondiabetics [31]
Despite the benefits of pharmacologic therapy arterialrevascularization remains a mainstay in the management ofCLI because the restoration of adequate blood flow to the footis crucial to provide pain relief promote wound healing andavoid amputation Although surgical revascularization is animportant therapeutic option recent data supports the use ofpercutaneous transluminal angioplasty which is both feasibleand safe in this setting [32ndash35] However recent reports fromthe literature seem to suggest the positive role of newcommercially available drugs in order to prevent ulceration indiabetic patientsThese findingsmight completely change thescenario in the future [36]
More aggressive techniques have been developed toimprove the results of percutaneous transluminal angioplastyin vessels below the knee Techniques such as subintimalangioplasty [37] retrograde approach with transpedal access[38] subintimal arterial flossing with antegrade-retrogradeintervention [39 40] transcollateral angioplasty [41] andpedal-plantar loop [42 43] are improving the success ratesof percutaneous transluminal angioplasty even in the mostdistal vascular territories
By theway control of any local sepsis through appropriateuse of surgical (debridement drainage and even amputation)and medical (antibiotics) modalities is always the immediatepriority in DF management [44]
Consequently timing has a key role for the diabeticrsquos foottreatment especially if it is infected
Faglia et al [45] have confirmed how in case of CLI(especially if it is associated with a severe infection) an earlysurgical treatment of the infection followed by early revas-cularization procedure can achieve limb salvage or a moredistal level of foot amputation Caravaggi [11] has proposedan ldquoIntegrated Surgical Approachrdquo that considers the mainaspects of treatment of severe foot infection time emergencysurgical treatment and revascularization procedures Sinceearly surgical treatment of infection is closely correlated withlimb salvage they have underlined that surgical debridementhas to be performed as soon as possible regardless of vascularcondition of the foot Revascularization procedures bothsurgical or endovascular are secondary in comparison to thelocal and systemic infections control
In conclusion the need for a coordinate multidisci-plinary care has long been obviousThe recent growth of ded-icated amputation prevention centers represents a positive
trend and new drugs could modify the natural history of thedisease
At the moment we would like to suggest a four-stepapproach to patients with DF
(1) Early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) Urgent treatment of severe foot infection with anaggressive surgical debridement
(3) Early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) Definitive treatment wound healing reconstructivesurgery and orthesis
This solution is also recommended by the most recentguidelines in particular by International Guidelines on thetreatment of diabetic foot and the Guidelines of the EuropeanSociety of Vascular and Endovascular Surgery of critical limbischemia and diabetic foot [46]
In our experience many different professional skillsshould work together 24 hndash365 d to reach the goal to avoidmajor amputations in patients with DF It is a hard andcomplex work but it is proven that only an interdisciplinaryintegrated diabetic foot Teammay lead to a significant impacton the outcome of our patients ldquoTime is Tissuerdquo
References
[1] World Health Organisation Fact sheet no 312 2011[2] L O Watkins ldquoEpidemiology and burden of cardiovascular
diseaserdquo Clinical Cardiology vol 27 no 6 pp III2ndashIII6 2004[3] J Stamler O Vaccaro J D Neaton and D Wentworth
ldquoDiabetes other risk factors and 12-yr cardiovascular mortalityfor men screened in the multiple risk factor intervention trialrdquoDiabetes Care vol 16 no 2 pp 434ndash444 1993
[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjects withtype 2 diabetes and in nondiabetic subjects with and withoutprior myocardial infarctionrdquo New England Journal of Medicinevol 339 no 4 pp 229ndash234 1998
[5] American Diabetes Association ldquoDiabetes 1993 Vital StatisticsrdquoADA publication no PMDIVS93 1993
6 International Journal of Vascular Medicine
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
Pre- or postulcerativelesion completelyepithelialized
Superficial wound notinvolving tendoncapsule or bone
Wound penetrating totendon or capsule
Wound penetrating tobone or joint
B Infection Infection Infection InfectionC Ischemia Ischemia Ischemia Ischemia
D Infection andischemia
Infection andischemia
Infection andischemia
Infection andischemia
patients have a high risk rate of both amputation and deathcompared with nondiabetics [31]
Despite the benefits of pharmacologic therapy arterialrevascularization remains a mainstay in the management ofCLI because the restoration of adequate blood flow to the footis crucial to provide pain relief promote wound healing andavoid amputation Although surgical revascularization is animportant therapeutic option recent data supports the use ofpercutaneous transluminal angioplasty which is both feasibleand safe in this setting [32ndash35] However recent reports fromthe literature seem to suggest the positive role of newcommercially available drugs in order to prevent ulceration indiabetic patientsThese findingsmight completely change thescenario in the future [36]
More aggressive techniques have been developed toimprove the results of percutaneous transluminal angioplastyin vessels below the knee Techniques such as subintimalangioplasty [37] retrograde approach with transpedal access[38] subintimal arterial flossing with antegrade-retrogradeintervention [39 40] transcollateral angioplasty [41] andpedal-plantar loop [42 43] are improving the success ratesof percutaneous transluminal angioplasty even in the mostdistal vascular territories
By theway control of any local sepsis through appropriateuse of surgical (debridement drainage and even amputation)and medical (antibiotics) modalities is always the immediatepriority in DF management [44]
Consequently timing has a key role for the diabeticrsquos foottreatment especially if it is infected
Faglia et al [45] have confirmed how in case of CLI(especially if it is associated with a severe infection) an earlysurgical treatment of the infection followed by early revas-cularization procedure can achieve limb salvage or a moredistal level of foot amputation Caravaggi [11] has proposedan ldquoIntegrated Surgical Approachrdquo that considers the mainaspects of treatment of severe foot infection time emergencysurgical treatment and revascularization procedures Sinceearly surgical treatment of infection is closely correlated withlimb salvage they have underlined that surgical debridementhas to be performed as soon as possible regardless of vascularcondition of the foot Revascularization procedures bothsurgical or endovascular are secondary in comparison to thelocal and systemic infections control
In conclusion the need for a coordinate multidisci-plinary care has long been obviousThe recent growth of ded-icated amputation prevention centers represents a positive
trend and new drugs could modify the natural history of thedisease
At the moment we would like to suggest a four-stepapproach to patients with DF
(1) Early diagnosis with a 24 h on call DF team All themembers of the team should be able to perform aduplex scan and to identify an infective disease ifpresent
(2) Urgent treatment of severe foot infection with anaggressive surgical debridement
(3) Early revascularization within 24 hours In all casesthe first line approach should be represented byendovascular procedures (PTA plusmn stenting)
(4) Definitive treatment wound healing reconstructivesurgery and orthesis
This solution is also recommended by the most recentguidelines in particular by International Guidelines on thetreatment of diabetic foot and the Guidelines of the EuropeanSociety of Vascular and Endovascular Surgery of critical limbischemia and diabetic foot [46]
In our experience many different professional skillsshould work together 24 hndash365 d to reach the goal to avoidmajor amputations in patients with DF It is a hard andcomplex work but it is proven that only an interdisciplinaryintegrated diabetic foot Teammay lead to a significant impacton the outcome of our patients ldquoTime is Tissuerdquo
References
[1] World Health Organisation Fact sheet no 312 2011[2] L O Watkins ldquoEpidemiology and burden of cardiovascular
diseaserdquo Clinical Cardiology vol 27 no 6 pp III2ndashIII6 2004[3] J Stamler O Vaccaro J D Neaton and D Wentworth
ldquoDiabetes other risk factors and 12-yr cardiovascular mortalityfor men screened in the multiple risk factor intervention trialrdquoDiabetes Care vol 16 no 2 pp 434ndash444 1993
[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjects withtype 2 diabetes and in nondiabetic subjects with and withoutprior myocardial infarctionrdquo New England Journal of Medicinevol 339 no 4 pp 229ndash234 1998
[5] American Diabetes Association ldquoDiabetes 1993 Vital StatisticsrdquoADA publication no PMDIVS93 1993
6 International Journal of Vascular Medicine
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
[6] A JM Boulton ldquoEnd-stage complications of diabetic neuropa-thy foot ulcerationrdquo Canadian Journal of Neurological Sciencesvol 21 no 4 pp S18ndashS22 1994
[7] American Diabetes Association ldquoDirect and indirect costs ofdiabetes in the United States in 1992rdquo ADA publication noPMDIC92 1992
[8] H J Murray and A J M Boulton ldquoThe pathophysiologyof diabetic foot ulcerationrdquo Clinics in Podiatric Medicine andSurgery vol 12 no 1 pp 1ndash17 1995
[9] N R Waugh ldquoAmputations in diabetic patients a review ofrates relative risks and resource userdquoCommunityMedicine vol10 no 4 pp 279ndash288 1988
[10] M E Levin ldquoPreventing amputation in the patient withdiabetesrdquo Diabetes Care vol 18 no 10 pp 1383ndash1394 1995
[11] C Caravaggi ldquoIntegrated surgical protocol for the treatment ofthe infected diabetic footrdquo Journal of Cardiovascular Surgeryvol 53 no 1 pp 23ndash30 2012
[12] J Y Poirier E Garin CDerrien et al ldquoDiagnosis of osteomyeli-tis in the diabetic foot with a 99mTc-HMPAO leucocytescintigraphy combined with a 99mTc-MDP bone scintigraphyrdquoDiabetes and Metabolism vol 28 no 6 pp 485ndash490 2002
[13] Standards of Medical Care in Diabetesd ldquoDiabetesrdquo 2012httpwwwoeglmkcatlaborADA-Standards-Diabetes-Care-2012
[14] S Vuorisalo M Venermo and M Lepantalo ldquoTreatment ofdiabeticfootulcersrdquo Journal of Cardiovascular Surgery vol 50no 3 pp 275ndash291 2009
[15] A L Lima P R Oliveira V C Carvalho et al ldquoMicrobiologyof diabeticfootinfections role of ertapenemrdquo Drugs Today vol49 supplement A pp 1ndash20 2013
[16] C Setacci E Chisci G de Donato F Setacci F Iacoponi andG Galzerano ldquoSubintimal angioplasty with the aid of a re-entrydevice for TASC C and D lesions of the SFArdquo European Journalof Vascular and Endovascular Surgery vol 38 no 1 pp 76ndash872009
[17] C Setacci G de Donato F Setacci and E Chisci ldquoIschemicfoot definition etiology and angiosome conceptrdquo Journal ofCardiovascular Surgery vol 51 no 2 pp 223ndash231 2010
[18] Joint News Release WHOIDF 2011[19] A J Boulton L Vileikyte G Ragnarson-Tennvall and J
Apelqvist ldquoThe global burden of diabetic foot diseaserdquo TheLancet vol 366 no 9498 pp 1719ndash1724 2005
[20] N Singh D G Armstrong and B A Lipsky ldquoPreventingfoot ulcers in patients with diabetesrdquo Journal of the AmericanMedical Association vol 293 no 2 pp 217ndash228 2005
[21] L Prompers N Schaper J Apelqvist et al ldquoPrediction ofoutcome in individuals with diabetic foot ulcers focus on thedifferences between individuals with and without peripheralarterial disease The EURODIALE Studyrdquo Diabetologia vol 51no 5 pp 747ndash755 2008
[22] D M Molenaar P J Palumbo and W R R E Wilson andRitts Jr ldquoLeukocyte chemotaxis in diabetic patients and theirnondiabetic first degree relativesrdquo Diabetes vol 25 no 2 pp880ndash883 1976
[23] J E Repine C C Clawson and F C Goetz ldquoBactericidalfunction of neutrophils from patients with acute bacterialinfections and from diabeticsrdquo Journal of Infectious Diseasesvol 142 no 6 pp 869ndash875 1980
[24] S Katz B Klein and I Elian ldquoPhagocytotic activity of mono-cytes from diabetic patientsrdquo Diabetes Care vol 6 no 5 pp479ndash482 1983
[25] R G Frykberg ldquoDiabetes foot ulcerationsrdquo in The High RiskFoot in Diabetes Mellitus R G Frykberg Ed pp 151ndash195Churchill-Livingstone New York NY USA 1991
[26] ldquoSecond European consensus document on chronic criticalleg ischemiardquo European Journal of Vascular Surgery vol 6supplement A pp 1ndash32 1992
[27] E W Gregg P Sorlie R Paulose-Ram et al ldquoPrevalence oflower-extremity disease in the US adult population ge40 yearsof age with and without diabetes 1999-2000 National Healthand Nutrition Examination Surveyrdquo Diabetes Care vol 27 no7 pp 1591ndash1597 2004
[28] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002
[29] N C Dolan K Liu M H Criqui et al ldquoPeripheral arterydisease diabetes and reduced lower extremity functioningrdquoDiabetes Care vol 25 no 1 pp 113ndash120 2002
[30] E Faglia F Favales A Quarantiello et al ldquoAngiographicevaluation of peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabeticsubjects with foot ulcersrdquo Diabetes Care vol 21 no 4 pp 625ndash630 1998
[31] J Malmstedt K Leander EWahlberg L Karlstrom L Alfreds-son and J Swedenborg ldquoOutcome after leg bypass surgeryfor critical limb ischemia is poor in patients with diabetes Apopulation-based cohort studyrdquoDiabetes Care vol 31 no 5 pp887ndash892 2008
[32] E Faglia L Dalla Paola G Clerici et al ldquoPeripheral angio-plasty as the first-choice revascularization procedure in diabeticpatients with critical limb ischemia prospective study of 993consecutive patients hospitalized and followed between 1999and 2003rdquo European Journal of Vascular and EndovascularSurgery vol 29 no 6 pp 620ndash627 2005
[33] F Dick N Diehm A Galimanis M Husmann J Schmidliand I Baumgartner ldquoSurgical or endovascular revascularizationin patients with critical limb ischemia influence of diabetesmellitus on clinical outcomerdquo Journal of Vascular Surgery vol45 no 4 pp 751ndash761 2007
[34] R Ferraresi M Centola M Ferlini et al ldquoLong-term outcomesafter angioplasty of isolated below-the-knee arteries in diabeticpatients with critical limb ischaemiardquo European Journal ofVascular and Endovascular Surgery vol 37 no 3 pp 336ndash3422009
[35] L Graziani and A Piaggesi ldquoIndications and clinical outcomesfor below knee endovascular therapy review articlerdquo Catheteri-zation and Cardiovascular Interventions vol 75 no 3 pp 433ndash443 2010
[36] S deFranciscis L Gallelli L Battaglia et al ldquoCilostazol preventsfoot ulcers in diabetic patients with peripheral vascular diseaserdquoInternational Wound Journal 2013
[37] A Bolia ldquoSubintimal angioplasty in lower limb ischaemiardquoJournal of Cardiovascular Surgery vol 46 no 4 pp 385ndash3942005
[38] M Montero-Baker A Schmidt S Braunlich et al ldquoRetrogradeapproach for complex popliteal and tibioperoneal occlusionsrdquoJournal of Endovascular Therapy vol 15 no 5 pp 594ndash6042008
[39] D J Spinosa N L Harthun E A Bissonette et al ldquoSubin-timal arterial flossing with antegrade-retrograde intervention(SAFARI) for subintimal recanalization to treat chronic critical
International Journal of Vascular Medicine 7
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
limb ischemiardquo Journal of Vascular and Interventional Radiol-ogy vol 16 no 1 pp 37ndash44 2005
[40] R Gandini V Pipitone M Stefanini et al ldquoThe ldquoSafarirdquo tech-nique to perform difficult subintimal infragenicular vesselsrdquoCardiovascular and Interventional Radiology vol 30 no 3 pp469ndash473 2007
[41] L Graziani A Silvestro L Monge et al ldquoTransluminal angio-plasty of peroneal artery branches in diabetics initial technicalexperiencerdquo Cardiovascular and Interventional Radiology vol31 no 1 pp 49ndash55 2008
[42] M Fusaro L Dalla Paola C Brigato et al ldquoPlantar to dorsalispedis artery subintimal angioplasty in a patient with criticalfoot ischemia a novel technique in the armamentarium of theperipheral interventionistrdquo Journal of Cardiovascular Medicinevol 8 no 11 pp 977ndash980 2007
[43] MManzi M Fusaro T Ceccacci G Erente L Dalla Paola andE Brocco ldquoClinical results of below-the knee intervention usingpedal-plantar loop technique for the revascularization of footarteriesrdquo Journal of Cardiovascular Surgery vol 50 no 3 pp331ndash337 2009
[44] M S Conte ldquoDiabetics revascularization endovascular versusopen bypassmdashdo we have then answerrdquo Seminars in VascularSurgery vol 25 pp 108ndash114 2012
[45] E Faglia G Clerici M Caminiti A Quarantiello M Ginoand A Morabito ldquoThe role of early surgical debridement andrevascularization in diabetic patients with deep foot spaceabscess retrospective review of 106 diabetic patientsrdquo Journalof Foot and Ankle Surgery vol 45 no 4 pp 220ndash226 2006
[46] M Lepantalo J Apelqvist C Setacci et al ldquoChapter V diabeticfootrdquo European Journal of Vascular and Endovascular Surgeryvol 42 supplement 2 pp S60ndashS74 2011
