Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 291-297

Analysis of factors delaying healing of ischemic foot wounds in patients who undergo lower limb revascularization


Jain Institute of Vascular Sciences, A Unit of Bhagwan Mahaveer Jain Hospital, Bengaluru, Karnataka, India

Date of Submission30-Sep-2019
Date of Acceptance21-Oct-2019
Date of Web Publication20-Dec-2019

Correspondence Address:
Dr. S Roshan Rodney
Jain Institute of Vascular Sciences, A Unit of Bhagwan Mahaveer Jain Hospital, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_65_19

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  Abstract 


Objective: Complete ulcer healing is one of the most important goals of treatment for chronic limb-threatening ischemia (CLTI). The purpose of this study was to analyze the factors of delayed wound healing in CLTI after successful revascularization. Methods: We analyzed factors affecting ischemic wound healing following successful revascularization through a prospective, nonrandomized, single–center, observational study conducted at Jain Institute of Vascular Sciences, Bengaluru, Karnataka, India. We have also analyzed wound healing rate, wound healing time (WHT), and limb salvage rate based on wound locations and WIfI stage in this study. 113 patients with CLTI (Rutherford category 5 and 6) who had undergone successful primary revascularization between August 2017 and August 2018 (13 months) were included in this study with a follow-up of 6 months. Results: The wound healing rates were 0% (1st month), 36.3% (3rd month), and 40.7% (6th month), and the cumulative wound healing rate was 77%. The median WHT was 95 days (WIfI Stage 3) and 105 days (WIfI Stage 4) and the overall limb salvage rate was 91.2%. Multivariate Cox proportional hazards analysis revealed the following as independent predictors of wound nonhealing after initial successful revascularization: WIfI stage 4 (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.2–0.4; P ≤ 0.001); diabetes mellitus (HR, 6.5; 95% CI, 1.3–32.08; P = 0.020); HbA1C >6.5 (HR, 5.1; 95% CI, 1.0–24.9; P = 0.043); and serum albumin <3.20 g/dl (HR, 2.9; 95% CI, 1.3–6.2; P = 0.008). Conclusions: Hence, we recommend that successful revascularization alone does not contribute to complete wound healing and other factors influencing ischemic wound healing have to be addressed and be a part of treatment armamentarium.

Keywords: Chronic, ischemia, revascularization, salvage, WIfI


How to cite this article:
Rodney S R, Anand V, Vishnu M, Raj S, Girija K R, Chaudhari HK, Lende V, Suresh K R. Analysis of factors delaying healing of ischemic foot wounds in patients who undergo lower limb revascularization. Indian J Vasc Endovasc Surg 2019;6:291-7

How to cite this URL:
Rodney S R, Anand V, Vishnu M, Raj S, Girija K R, Chaudhari HK, Lende V, Suresh K R. Analysis of factors delaying healing of ischemic foot wounds in patients who undergo lower limb revascularization. Indian J Vasc Endovasc Surg [serial online] 2019 [cited 2020 Feb 20];6:291-7. Available from: http://www.indjvascsurg.org/text.asp?2019/6/4/291/273600




  Introduction Top


Complete ulcer healing is one of the most important goals of treatment for chronic limb-threatening ischemia (CLTI).[1] Among the many studies that have reported limb salvage, complete ulcer healing was reported in only 17 studies (0.9%) according to a literature search from 1985 to 2005.[2] Historically, the outcomes of patients with peripheral arterial disease have been evaluated primarily with technical parameters such as graft patency or target lesion revascularization (TLR).[3] In patients with CLTI, clinical limb outcome was considered successful when the limb was rescued from major amputation. However, the “limb salvage rate” does not always represent successful limb outcome, because a significant number of patients die before their symptoms are relieved.[4],[5] Attempts to determine the independent factors that affect limb salvage have failed because these factors are overshadowed by survival factors. Moreover, amputation-free survival also does not always indicate successful limb outcomes, because patients may survive a long time without major amputation, but with painful ischemic wounds.[6] The achievement of wound healing is a clear-cut indicator for evaluating the outcome of limbs with ischemic wounds.[7],[8] The aim of the current study was to analyze the various factors delaying healing of ischemic foot wounds after successful revascularization.


  Methods Top


A prospective, nonrandomized, single–center, observational study was conducted at Jain Institute of Vascular Sciences, Bengaluru, Karnataka, India. All patients with CLTI (Rutherford category 5 and 6) who had undergone primary successful revascularization between August 2017 and August 2018 (13 months) were included in this study. Patients who had previous revascularization of index limb, who do not consent for the study, and unsuccessful revascularizations were excluded. The study protocol was approved by the institutional review board. Informed consent for this study was obtained from each patient.

During the study period of 13 months, 198 CLTI patients presenting with ischemic foot wounds were treated with revascularization and appropriate wound management. After exclusion, 113 CLTI patients who had undergone successful revascularization were enrolled [Figure 1]. Strategy for revascularization was decided by consensus among our team of vascular surgeons depending on general condition, comorbidity, and extent of ischemia. The age, sex, comorbidities, tobacco use, Rutherford class of critical ischemia, WIfI stage, and various laboratory parameters were recorded. Wounds were divided into three groups according to their location.

  • Group A comprised wounds localized only to the toes
  • Group B comprised wounds localized only to the heel
  • Group C comprised wounds extending onto the fore/mid-foot along the dorsal or plantar surfaces or multiple wounds.[9]


Patients were divided into two groups as wound healed and wound not healed groups to analyze the factors delaying wound healing.[1] The primary outcome of factors associated with delayed wound healing after successful revascularization was examined by multivariate analysis. The secondary outcome measures of this study were wound healing rate, median wound healing time (WHT) after revascularization, and limb salvage rate.
Figure 1: Patient selection flowchart

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Clinical variables found to influence wound healing in previous studies were inserted into the multivariate analysis. All patients were followed up at the 1st, 3rd, and 6th months. Written documentation and digital photographs were recorded during each visit. All patients received standardized wound management according to the institute protocol.

Patients will undergo continuous ambulatory 24 h blood sugar monitoring (Freestyle Libre system) for 2 weeks postoperatively to start with and serial home general random blood sugar (GRBS) according to institute protocol to assess whether good glycemic control in postoperative period results in better wound healing.

Definitions

Complete wound healing was defined as complete epithelialization of the tissue defect by secondary intention vacuum assisted closure [e g., vacuum assisted closure (VAC)] or tertiary intention (e g., skin grafting) or after any additional local debridement.[2] Wounds were considered not healed if they failed to heal within 6 months or in case of major amputation or death before complete healing.[4],[10] WHT was defined as the number of days required to achieve complete wound healing after revascularization.[9] Limb salvage was defined as prevention of major amputation. Limbs that required debridement/minor amputation (toe, ray, or transmetatarsal amputation) but ultimately healed were considered successful limb salvage; major amputation was defined as limb loss below or above the knee level.[10]

Statistical analysis

All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc. version 18.5, Chicago, IL, USA). Multivariate Cox proportional hazards regression models were used to investigate the association of variables with wound nonhealing. Variables with statistical significance in the multivariate model were determined as independent risk factors for outcome. P <0.05 was considered statistically significant.


  Results Top


Baseline characteristics

A total of 113 patients were evaluated during the study period, among which 87 patients' wounds were healed completely [Figure 1].

There was no significant difference between the two groups in terms of age. The prevalence of diabetes, hypertension, and ischemic heart disease was significantly higher in the wound not healed group. Majority of the patients were males and had a history of tobacco consumption in this analysis, henceforth showing significant difference in terms of sex and tobacco consumption between both groups [Table 1].
Table 1: Baseline characteristics of the wound healed and not healed groups

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Majority of the patients were belonging to Rutherford Category 6 (78% in the wound healed group and 96% in the wound not healed group), but in terms of wound nonhealing, there was significantly higher prevalence of Rutherford 6 as compared to Rutherford 5. Most patients were in WIfI Stage 3 (38%) and WIfI Stage 4 (40%). Wound healed group had 33% and wound not healed group had 61% patients in the WIfI Stage 4, which was statistically significant. Regarding wound location, majority of wounds were in Location C. Significant difference was observed in terms of wound healed and not healed in all wound locations more so in Location B (heel) wounds wherein 21% of wounds were not healed and only 3.4% of wounds in Location B had healed [Table 2].
Table 2: Baseline characteristics, limb demographics, and wound characteristics in the wound healed and not healed groups

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Regarding ambulatory sugars/home GRBS monitoring postoperative 2 weeks, the difference was not statistically significant as both groups of patients had almost equally matched, controlled, and uncontrolled sugars probably due to lesser sample size for analysis. Graphical representation of ambulatory glucose profile is depicted in [Figure 2].
Figure 2: Graphical representation of ambulatory glucose profile which demonstrate the median level of control and provide an index of variability in control at every hour of a typical day, both inter- and intraday variability

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Predictors of delayed wound healing after revascularization

Multivariate Cox proportional hazards analysis revealed the following as independent predictors of wound nonhealing after initial successful revascularization: WIfI Stage 4 (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.2–0.4; P ≤ 0.001); diabetes mellitus (DM) (HR, 6.5; 95% CI, 1.3–32.08; P = 0.020); HbA1C >6.5 (HR, 5.1; 95% CI, 1.0–24.9; P = 0.043); and serum albumin <3.20 g/dl (HR, 2.9; 95% CI, 1.3–6.2; P = 0.008 [Table 3]).
Table 3: Negative predictors of wound healing per multivariate cox proportional hazards model

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Overall 76.99% of the wounds were healed and 7.07% of the wounds were not healed at the end of 6 months. 8.84% of patients had major amputation and 7.07% of patients had died during the follow-up [Table 4].
Table 4: Patients limb, wound, and survival outcome after successful revascularization

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Wound healing rates were 0% (1st month), 36.3% (3rd month), and 40.7% (6th month), respectively, and the cumulative wound healing rate was 77% [Figure 3]. The median WHT based on wound location was 45 days (Location A), 45 days (Location B), and 98 days (Location C) [Figure 4]. The median WHT based on WIfI Stage was 45 days (Stage 1), 47 days (Stage 2), 95 days (Stage 3), and 105 days (Stage 4) [Figure 5].
Figure 3: Wound healing rate. The wound healing rates were 0% (1st month), 36.3% (3rd month), and 40.7% (6th month), respectively, and the cumulative wound healing rate was 77%

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Figure 4: Wound healing time. The median wound healing time based on wound location were 45 days (Location A), 45 days (Location B), and 98 days (Location C)

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Figure 5: Wound healing time. The median wound healing time based on WIfI Stage were 45 days (Stage 1), 47 days (Stage 2), 95 days (Stage 3), and 105 days (Stage 4)

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During the study period, 10 (8.8%) patients underwent major amputation amounting to a 91.2% cumulative limb salvage rate. Ninety-seven percent of the patients had their limb salvaged at the end of 1st month, which became 94% at the end of 3rd month and only 91% at the end of 6th month [Figure 6]. Based on wound location, 100% of patients who had their wounds in Location A achieved limb salvage in comparison to Location B (88.9%) and Location C (89.4%) [Figure 7].
Figure 6: Limb salvage rate. The limb salvage rate were 97%, 94%, and 91% at the end of 1st, 3rd, and 6th month

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Figure 7: Wound location and limb salvage. The limb salvage rate based on wound location were 100% (Location A), 88.9% (Location B), and 89.4% (Location C)

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Based on WIfI Stage, 100% of patients in Stage 1 and 2 had their limb salvaged in comparison to Stage 3 (97.7%) and Stage 4 (80%) [Figure 8].
Figure 8: WIfI stage and limb salvage. The limb salvage rate based on WIfI stage were 100% (Stage 1), 100% (Stage 2), 87.7% (Stage 3), and 80% (Stage 4)

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Of the total 87 patients who had their wound healed, only 73% of patients who had infected wound preoperatively had achieved wound healing in comparison to 95% who wounds were not infected [Figure 9]. 100% of patients had their limb salvaged who had uninfected preoperative wounds and only 89.2% of patients had their limb salvaged whose wounds were infected [Figure 10].
Figure 9: Wound status (infection) and wound healing rate

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Figure 10: Wound status (infection) and limb salvage

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  Discussion Top


Wound healing after revascularization has not been fully studied even though it is one of the most important outcomes of CLTI treatment. Clinical outcomes in patients with CLTI depend not only on restoration of macrovascular blood flow but also on aggressive periprocedural wound care.[11]

In our study, independent negative predictors of wound healing were determined by multivariable Cox proportional hazards model and identified the following as predictors: WIfI stage 4 (HR, 0.32; 95% CI, 0.2–0.4; P < 0.001); DM (HR, 6.5; 95% CI, 1.3–32.08; P = 0.020); HbA1C >6.5 (HR, 5.1; 95% CI, 1.0–24.9; P = 0.043); and serum albumin <3.20 g/dl (HR, 2.9; 95% CI, 1.3–6.2; P = 0.008).

Das et al.[1] in their study of predictors of delayed wound healing after successful isolated below-the-knee endovascular intervention in patients with ischemic foot ulcers identified the following as predictors of wound nonhealing after initial EVT: ESRD with dialysis (HR, 2.6; 95% CI, 1.0–6.3; P = 0.04); albumin level <3.0 g/dL (HR, 2.0; 95% CI, 1.1–3.8; P = 0.02); CRP level >5.0 mg/dL (HR, 3.9; 95% CI, 1.6–9.6; P = 0.003); major tissue loss (HR, 2.1; 95% CI, 1.3–3.4; P = 0.003); wound infection (HR, 1.9; 95% CI, 1.2–2.9; P = 0.005); gangrene (HR, 1.8; 95% CI, 1.2–2.8; P = 0.008); wound depth (UT grade 3; HR, 3.4; 95% CI, 1.4–8.6; P = 0.009); duration of ulcer ( ≥ 2 months; HR, 2.9; 95% CI, 1.0–8.4; P = 0.048); insulin use (HR, 1.7; 95% CI, 1.0–2.8; P = 0.04); and no BTA runoff (HR, 1.9; 95% CI, 1.0–3.4; P = 0.04).

Serum albumin <3.2 g/dl was strongly associated with wound nonhealing in the current study. Azuma[12] also reported albumin <3 g/dL as a negative predictor for wound healing after bypass surgery; however, it is unknown whether hypoalbuminemia was caused by inflammation or malnutrition.

Kobayashi et al.[9] analyzed WHT and 1-year wound healing rate by wound, ischemia, and foot infection clinical stage and found that as WIfI stage increased, so did WHT (all weighted means, Stage 1: 92.89 days (range 31–112), Stage 1: 94.32 (range 49–133), Stage 3: 141.30 days (range 125–163), and Stage 4: 207.88 days (range 111–263)). The WHR at 1 year decreased with increasing WIfI stage (all weighted means, Stage 1: 92.0%, Stage 2: 69.32%, Stage 3: 62.38%, and Stage 4: 44.89%). In our study, the wound healing rate in patients with WIfI Stage 3 and Stage 4 were 79 and 64%, respectively. The median WHT was 95 days and 105 days in patients belonging to WIfI Stage 3 and 4. Overall limb salvage rate was only 80% in WIfI Stage 4. Our results showed that WIfI wound grade affected the achievement of wound healing, limb salvage, and WHT directly and independently.

In the clinical setting, we generally divide wounds into two groups using the Rutherford classification, that is, into Rutherford 5 or Rutherford 6. However, the Rutherford classification is ambiguous and sometimes it is difficult to clearly categorize wounds into two groups because there are various types of wounds and sometimes multiple wounds on a single limb. In our study, we divided wounds into three groups according to their locations: Group A (toe wounds, n = 17), Group B (heel wounds, n = 8), and Group C (extensive wounds extending onto the fore- or mid-foot along with dorsum or plantar surfaces or multiple wounds, n = 88) and revealed statistically significant (P = 0.002) results of wound healing rates, although there were differences in baseline characteristics.

Wound healing rates at 6 months were 90% (Group A), 33% (Group B), and 79% (Group C) (P = 0.024). The median WHT was 45 days (Group A and B) and 98 days (Group C), which was comparable to the study conducted by Kobayashi et al.,[9] which showed wound healing rates 75%, 52%, and 13% in Group T, Group H, and Group E, respectively. The median time to healing was 64 days (interquartile range 25–156 days) in Group T, 168 days (interquartile range 123–316 days) in Group H, and 267 days (interquartile range 177–316 days) in Group E (P = 0.038).

These findings suggest that evaluation of wound locations is meaningful for the prediction of wound healing.

Ulceration or gangrene located at the heel is considered difficult to treat. Söderström et al.[10] showed that ischemic tissue lesions located on the mid- and hind-foot had significantly prolonged ulcer healing times (HR, 0.4, P = 0.044). Our findings are in agreement with those of Söderström et al.[10] and they indicated that the rate of healing of heel wounds was lower than that of toe wounds (37.5% vs. 100%). And that, it took a considerably longer time to heal. This difficulty with successful healing most likely reflects many factors – limited soft tissue over the calcaneus, the frequent development of osteomyelitis, difficulty in keeping pressure off the wound, and differences in regional pedal perfusion.

In studies done by Shiraki et al.[4] and Okazaki et al.,[3] 42% of their patients wounds were infected. Das et al.[1] observed wound infection in 32.6% and 77.8% in their wound healing and wound nonhealing groups. In our study, wound infection was present in 78% and 96% of patients in the wound healed and wound not healed groups, respectively (P = 0.035). Diagnosis of wound infection was further proven by elevated preoperative white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein levels in all the patients in wound not healed group. Preoperative positive wound culture and osteomyelitis was present in 100% (P = 0.056) and 39% (P = 0.001) of wounds, respectively.

The present study represents one of the few prospective studies of ischemic ulcer healing after revascularization. After revascularization for CLTI, the wound healing rate at 1 month, 3 months, and 6 months were 0%, 36.3%, and 40.7%, respectively, and the cumulative wound healing rate was 77%.

Historically, the outcomes of patients with peripheral arterial disease have been evaluated primarily with technical parameters such as graft patency or TLR. In patients with CLTI, clinical limb outcome was considered successful when the limb was rescued from major amputation. However, the “limb salvage rate” does not always represent successful limb outcome, because a significant number of patients die before their symptoms are relieved. The uncertainty about limb salvage in the subgroup of patients who die before symptom relief (wound healing or pain relief) makes the analysis of limb outcome difficult.

The incidence of major amputation and death before achieving complete healing during the follow-up period was 10 limbs (8.8%) and 87 of the 113 limbs (77%) achieved complete wound healing. Of the 26 patients who did not achieve wound healing, wound observation was terminated by amputation in 10 and by death in 8, and 8 patients still had unhealed ulcer at 6 months after primary revascularization. Kobayashi et al.[9] found the incidence of major amputation and death before achieving complete healing during the follow-up period were 6 limbs (5.7%) and 24 patients (28.6%) in Group T, 2 limbs (9.5%) and 5 patients (29.4%) in Group H, and 19 limbs (47.5%) and 24 patients (64.9%) in Group E. On stratifying, patients who had major amputations according to wound locations were 0 [Group A], 1 (12.5%) (Group B), and 9 (10.2%) (Group C). In this study, the major amputation rate after revascularization was significantly different between wounds with versus without infection (10.8% vs. 0%, respectively). In our study, majority of patients were belonging to WIfI Stage 3 and Stage 4. Major amputation rate was 2.4% (WIfI Stage 3) and 20% (WIfI Stage 4). The cumulative limb salvage rate at 6 months in our study was 91%.

We also analyzed the ambulatory blood glucose profile for few CLTI patients who consented for the device sensor whereas the rest monitored by home GRBS monitoring. Ambulatory glucose profile (AGP) is one of the most recent, innovative developments that are being used to monitor glycemic variability in DM patients.[13] AGP is generated from the flash glucose monitoring device which is attached to the patient for a maximum period of 14 days, which checks the sugars at every 15 min.[13] In our study, 75.9% of patients had controlled mean sugars at the end of 2 weeks, whereas 24.1% of patients had uncontrolled sugars. Out of the wounds which were healed, 72.5% of patients had their sugars controlled as per the ambulatory glucose profile/home GRBS monitoring, and out of the wounds which were not healed, 14.3% of patients had uncontrolled sugars although the difference was not statistically significant. AGP in the patient provides the doctor with an opportunity to have a complete glycemic picture of the patient. It offers a reliable, predictive, standardized visualization of the glucose data.

Limitations

Several limitations of our study must be acknowledged. This study was a single-center study and selection of revascularization procedure was not randomized. Patient background was not controlled. Revascularization procedure, target artery, and wound management were not stratified. WHT may be overestimated because wound status was not checked daily in outpatients and depending on the frequency of clinic visits, may have introduced error of up to approximately 1 month.


  Conclusions Top


Awareness of the systemic and local factors influencing wound healing would enable optimal wound management, leading to successful wound healing and improved limb salvage and survival rates. The above viewpoints regarding ulcer healing must be incorporated into the next CLTI treatment guideline to prepare for a coming era of vascular disease related to the global expansion of an aging population with increasing comorbid diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Das SK, Yuan YF, Li MQ. Predictors of delayed wound healing after successful isolated below-the-knee endovascular intervention in patients with ischemic foot ulcers. J Vasc Surg 2018;67:1181-90.  Back to cited text no. 1
    
2.
Elbadawy A, Ali H, Saleh M, Hasaballah A. Editor's choice – A prospective study to evaluate complete wound healing and limb salvage rates after angiosome targeted infrapopliteal balloon angioplasty in patients with critical limb ischaemia. Eur J Vasc Endovasc Surg 2018;55:392-7.  Back to cited text no. 2
    
3.
Okazaki J, Matsuda D, Tanaka K, Ishida M, Kuma S, Morisaki K, et al. Analysis of wound healing time and wound-free period as outcomes after surgical and endovascular revascularization for critical lower limb ischemia. J Vasc Surg 2018;67:817-25.  Back to cited text no. 3
    
4.
Shiraki T, Iida O, Takahara M, Soga Y, Yamauchi Y, Hirano K, et al. Predictors of delayed wound healing after endovascular therapy of isolated infrapopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemodialysis. Eur J Vasc Endovasc Surg 2015;49:565-73.  Back to cited text no. 4
    
5.
Iida O, Nakamura M, Yamauchi Y, Kawasaki D, Yokoi Y, Yokoi H, et al. Endovascular treatment for infrainguinal vessels in patients with critical limb ischemia: OLIVE registry, a prospective, multicenter study in Japan with 12-month follow-up. Circ Cardiovasc Interv 2013;6:68-76.  Back to cited text no. 5
    
6.
Apelqvist J, Elgzyri T, Larsson J, Löndahl M, Nyberg P, Thörne J, et al. Factors related to outcome of neuroischemic/ischemic foot ulcer in diabetic patients. J Vasc Surg 2011;53:1582-800.  Back to cited text no. 6
    
7.
Azuma N, Uchida H, Kokubo T, Koya A, Akasaka N, Sasajima T. Factors influencing wound healing of critical ischaemic foot after bypass surgery: Is the angiosome important in selecting bypass target artery? Eur J Vasc Endovasc Surg 2012;43:322-8.  Back to cited text no. 7
    
8.
Kawarada O, Fujihara M, Higashimori A, Yokoi Y, Honda Y, Fitzgerald PJ. Predictors of adverse clinical outcomes after successful infrapopliteal intervention. Catheter Cardiovasc Interv 2012;80:861-71.  Back to cited text no. 8
    
9.
Kobayashi N, Hirano K, Nakano M, Muramatsu T, Tsukahara R, Ito Y, et al. Wound healing and wound location in critical limb ischemia following endovascular treatment. Circ J 2014;78:1746-53.  Back to cited text no. 9
    
10.
Söderström M, Aho PS, Lepäntalo M, Albäck A. The influence of the characteristics of ischemic tissue lesions on ulcer healing time after infrainguinal bypass for critical leg ischemia. J Vasc Surg 2009;49:932-7.  Back to cited text no. 10
    
11.
Attinger C. Comment on: 'Factors influencing wound healing of critical ischaemic foot after bypass surgery: Is the angiosome important in selecting bypass target artery? Eur J Vasc Endovasc Surg 2013;45:99.  Back to cited text no. 11
    
12.
Azuma N. Response to letter to the editor: 'Factors influencing wound healing of critical ischaemic foot after bypass surgery: Is the angiosome important in selecting bypass target artery?'. Eur J Vasc Endovasc Surg 2013;45:99-100.  Back to cited text no. 12
    
13.
Saboo B, Sheth SV, Joshi S, Bhandari S, Kesavadev J, Maheshwari A, et al. Use of ambulatory glucose profile for improving monitoring and management of T2DM. J Assoc Physicians India 2018;66:69-71.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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