Clinical value of Tc-99m MIBI scintigraphy for the level of lower limb amputation in patients with diabetic foot ulcers

Clinical value of Tc-99m MIBI scintigraphy for the level of lower limb amputation in patients with diabetic foot ulcers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical value of Tc-99m MIBI scintigraphy for the level of lower limb amputation in patients with diabetic foot ulcers mehmet ekici, ali eray günay, seyhan karaçavuş, hümeyra gençer, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4165516/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background There is a positive relationship between mitochondrial damage in the cell and uptake in 99m Tc-MIBI scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers. 99m Tc-MIBI scintigraphy should be considered in order to decide on the level of amputation. Methods Prospectively twenty-four patients with diabetic foot ulcers (DFUs) were included in the study. As a result of treatment that started with the hospitalization, patients whose DFUs healed and did not need surgical intervention were determined as group 1, and patients whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention were determined as Group 2. 99mTc-MIBI scintigraphy was obtained before surgery. The 99m Tc-MIBI uptake rates of the injured foot relative to the healthy foot were recorded. Deep tissue culture was taken at surgery. ESR, WBC, CRP and albumin values of the patients were measured. Results In this study, 99m Tc-MIBI uptake rates of patients with poor prognosis were higher at all times than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates. While the CRP level was 86.04 ± 21.87 mg / dL in Group 1, it was measured as 144.43 ± 27.54 mg / dL in Group 2 (p = 0,040). There is a positive correlation between ulcerated foot / healthy foot 99mTc-MIBI involvement rates at 10 and 30 seconds and CRP values, and a negative correlation between albumin values. Conclusion There is a significant relationship between 99m Tc-MIBI involvement rates and poor prognosis and reamputation. The correlation between CRP and albumin levels which are among the predictive values, and 99m Tc-MIBI uptake confirms this relationship. In diabetic foot ulcers, which are difficult to management and treatment. amputation diabetic foot ulcer MIBI 99mTc-MIBI scintigraphy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Diabetes mellitus (DM) is an important public health problem with an increasing incidence worldwide [1]. Even a small DFU can compromise the viability of the entire foot [1,2]. The risk of death within 5 years for a patient with DFU is 2.5 times higher than that for a patient with DM without a foot ulcer [1,3]. The worst possible potential outcome of DFU, other than death, is lower-extremity amputation (LEA) [1,4]. Approximately 20% of patients with DFU require LEA [1–3,5]. DFU-related amputations constitute 40%–[85% of nontraumatic amputations [1,3–6]. Once amputated, the incidence of a second amputation in the contralateral limb reaches 50% within 2 years [3,5,6]. Amputation negatively affects the quality of life of patients with DFU Predicting the level of DFU-related amputation can reduce amputation rates by observation and prophylactic action for the high-risk groups [1–4]. Many studies have explored efforts to prevent foot amputation and determine risk factors associated with amputation [1–7]. Clinical history and physical examination, transcutaneous oxygen pressure measurement, Doppler ultrasonography (USG), computed tomography (CT), contrasted CT angiography, and venography, magnetic resonance imaging (MRI), MRI angiography, carbon dioxide angiography, and lower extremity (LE) duplex scanning are the methods frequently used in the evaluation of peripheral vascular disease [2–9]. In addition, various nuclear medicine techniques are also used [5,7–14]. Technetium 99m monomer methoxy isobutyl isonitrile ( 99m Tc-MIBI), also known as 99m Tc sestamibi, is a radiopharmaceutical used to evaluate pathology in heart, breast, and parathyroid [7,8,12–16]. 99mTc-MIBI is part of a class of radioactive diagnostic agents characterised as lipophilic cationic radiotracers.[12–14]. 99m Tc-MIBI is localized to intramitochondrial anionic proteins in cells [8,12–14]. Cellular uptake is proportional to regional blood flow, mitochondrial activity, and cellular viability [8]. 99m Tc-MIBI is not organ-specific and is inversely correlated with mitochondrial function [8,12]. There are studies evaluating musculoskeletal system perfusion and viability using 99mTc-MIBI in patients with DM [7,15] and both with and without DM [8,14,16,17].. With this study, we aimed to determine the predictability of the amputation level to reduce the risk of amputation and develop better treatment strategies in patients with DFU. For this purpose, we evaluated the perfusion and viability of skeletal muscles using 99m Tc-MIBI in patients with DFU and tried to determine the relationship between the uptake rates recorded with 99m Tc-MIBI scintigraphy and amputation level and reamputation. Methods Patients A total of 35 patients hospitalized for DFU between January 2020 and March 2020 in the Diabetic Foot Wound Clinic of our hospital were included in the study and evaluated prospectively. At the end of the first year, 11 patients who were lost to follow-up because of the COVID-19 pandemic were excluded from the study, and the study was completed with 24 feet (19 men, 5 women; 12 right sides, 12 left sides; mean age, 63.4 ± 11.3 years; range, 42–86 years) of 24 patients. Study design As a result of treatment that started with the hospitalization, patients whose DFUs healed and did not need surgical intervention were determined as group 1, and patients whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention were determined as group 2. Group 2 consisted of patients who received antibiotherapy for the isolated agent, received anticoagulant therapy, did not recover despite repeated debridements, daily dressings and supportive treatments (such as HBO) and needed high-level amputation. The inclusion criteria were as follows: patients with diabetic foot ulcer, no previous surgical procedure, diagnosis of type 2 DM, age ≥ 18 years. The exclusion criteria were as follows: type 1 DM, DFU in both lower extremities, pregnancy, or lactation patients, a history of malignancy, a history of sepsis, non DM ischemic peripheral artery disease, and any known history of allergy or a history of hypersensitivity to proteins. Data measurement Patients’ age, sex, smoking history, DM duration, DFU side, Wagner classification, previous amputation history, peripheral arterial disease (PAD), laboratory values, microbiologic culture results, and medical comorbidities were collected. In the laboratory evaluation, hemoglobin (Hb), white blood cell (WBC), plasma albumin (ALB), glycosylated hemoglobin A1c (HbA1c), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), eGFR, creatinin, Ankle Brachial Index (ABI), peak systolic velocitieslevels were measured. The Doppler ultrasound results for Arteria Femoralis, Arteria Poplitealis, Arteia Tibialis Posterior (ATP), Arteria Doraslis Pedis (ADP), and Arteria Tibialis Anterior (ATA) were recorded as triphasic, biphasic, and monophasic. LE radiographs and MRI were used to evaluate the presence of neuropathic arthropathy (Charcot arthropathy) or osteomyelitis. LE USG was used to evaluate PAD. The SVS classification system, which emerged in 2013 and was formally introduced in an SVS publication in 2014, addresses three critical factors contributing to the risk of limb amputation: wound, ischemia, and foot infection. The SVS WIfI classification assigns a 4-grade scale to each parameter, ranging from 0 to 3, with 0 indicating absence, 1 denoting mild, 2 indicating moderate, and 3 representing severe [18]. 99m Tc-MIBI scintigraphy Double-headed single-photon emission tomography/computed tomography (SPECT/CT; Mediso AnyScan®SC) was used for imaging. Tetrakis (2-methoxyisobutyl isonitrile) copper (I) tetrafluoroborate (1.0 mg, MON.MIBI KIT; Eczacıbaşı Monrol) was labeled with 99m Tc radionuclide obtained by daily milking from the Mo-Tc generator. After the patients were placed in the appropriate position, the detectors using the low-energy high-resolution collimator were positioned at 180°, and the foot area was focused in the anterior–posterior positions. After the parenteral administration of 20 mCi 99m Tc-MIBI, dynamic imaging was started. Data were collected from the anterior and posterior projections in a 15-s 30-frame, 128 × 128 matrix, without using a zoom factor. After dynamic imaging, 300 s of static imaging was performed in anterior–posterior positions. Subsequently, SPECT/CT images were acquired without changing the patient’s position (Fig. 1 ). The obtained images were analyzed using the Interview 2.0 program on the workstation connected to the Mediso AnyScan®SC gamma camera. An intact extremity was taken as a reference for evaluation. Relevant areas of the extremity with DFU and the contralateral healthy extremity were taken and proportioned. The peak activity values at the 10th and 30th seconds were taken as a basis. This process was performed separately for anterior and posterior imaging, and the arithmetic mean of the values was calculated. Time–activity curves were obtained for all analyses. With 99m Tc-MIBI scintigraphy, the 99m Tc-MIBI uptake rates of the foot of the diabetic ulcerated extremity side/foot of healthy extremity side, distal ankle of diabetic ulcerated extremity side/proximal ankle of diabetic ulcerated extremity side, and extremity of the diabetic ulcerated side/extremity of healthy side were measured at 10 and 30 s, respectively. Two nuclear medicine consultants unaware of the data evaluated the scintigraphic studies and reached the final impression by consensus. The uptake rates of 99m Tc-MIBI scintigraphy at the 10th and 30th seconds will be compared between Group 1 and Group 2. The relationship between these rates and the need for upper-level amputation will be demonstrated with 99m Tc-MIBI. Ethical issues The study protocol was approved by the Erciyes University Faculty of Medicine, Clinical Research Ethics Committee (Approval date/no. January 16, 2020/30) and conducted in accordance with the principles of the Declaration of Helsinki. Statistical analysis Data analyses were conducted with IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, USA). Percentages and standard deviations were determined for categorical data and continuous variables, and the Shapiro–Wilk test, and histograms were used to evaluate data distribution. Pearson’s chi-square test compared categorical data between the groups. After the difference between repeated measurements was analyzed with the Friedman test, pairwise comparisons were made with the Dunn test. The Mann–Whitney U test was used to examine the difference between nondependent groups. The relationship between laboratory results and 99m Tc-MIBI uptake results was evaluated by the Spearman correlation analysis. A value of p < 0.05 was considered statistically significant. Results The mean hospital stay was 14.6 ± 2.1 (range, 3–45) days. Table 1 summarizes the baseline characteristics of the patients. Before the patients' clinical admissions, the average wound duration was calculated to be 3.04 ± 1.03 months. Moreover, 6 (25%) patients required a repeat surgical procedure. Of the 3 patients who underwent toe amputation, 2 underwent transmetatarsal amputation and one patient underwent below-knee amputation. One patient who underwent transmetatarsal amputation underwent below-knee amputation. Two patients who underwent below-knee amputation underwent below-knee amputation. Table 1 Patients’ demographic characteristics. Variables Group 1 Group 2 Total p -value Number of patients 18 6 24 Age, years, mean ± SD 61.6 ± 2.5 69.2 ± 3.9 63.4 ± 11.3 0.060 a Sex, n Women Men 4 14 1 5 5 19 0.634 b Smoking history, n (%) Present Absent 9 9 2 4 11 13 0.649 b Duration of DM (yr), mean ± SD 10.8 ± 1.8 15.9 ± 5.2 12.1 ± 9.2 0.494 a Number of comorbidities, n 1 2 3+ 7 8 3 1 2 3 8 10 6 0.353 b Side of involvement, n Right Left 6 12 6 0 12 12 0.014 b HbA1c (%), mean ± SD 8.9 ± 0.5 7.7 ± 0.6 8.6 ± 2.1 0.280 a SD, standard deviation; DM, diabetes mellitus; HbA1c, glycated hemoglobin; a Mann-Whitney U test; b Chi-square test While the patients’ baseline WBC, ESR, and CRP levels decreased over time, the ALB level increased. Laboratory values at the end of the follow-up were significantly different from the initial values (Table 2 ). Table 2 Laboratory results of the patients during follow-up. Variables BT AT Month 1 AT Month 3 AT Month 6 p -value † WBC [10 3 /µL] median (range) 9.6 (4.3–30) 7.7 (3.9–18.4) 7.5 (4–17.7) 8.5 (4.1–22) * 0.044 ESR [mm/hr] median (range) 58.5 (4–140) 31 (4–138) 19 (2–198)* 15 (2.8–140)* 0.001 CRP [mg/L] median (range) 79.35 (2–322) 14.4 (0.7–170) 8.85 (1.1–154)* 6.95 (0.9–267)* 0.001 ALB [g/L] median (range) 34.2 (27–44) 35 (25–45) 39 (23–45) 38.5 (18–47)* 0.036 BT, before treatment; AT, after treatment; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ALB , albumin; † Friedman test; * The difference compared to BT was statistically significant. When the mean CRP and ALB levels of the groups were compared before the treatment, the CRP level in the reoperated group was significantly higher and the ALB level was low (ALB, 35.81 ± 1.32 (range, 28–44) vs. 32.4 ± 1.53 (range, 27–37), respectively, p = 0.224; CRP, 86.04 ± 21.87 (range, 2–232) vs. 144.43 ± 27.54 (range, 107–281), respectively, p = 0.04). Patients' average eGFR values during clinical admissions were calculated as 53.12 ± 13.53 ml/min. The mean creatinine level was 1.15 ± 0.35 mg/dL. The average hemoglobin level was measured at 11.06 ± 1.73 g/dL. In the deep tissue cultures of the patients, Gram-negative bacteria (Escherichia coli, Psödomonas aeruginosa etc.) were detected in 7 (29.1%) patients and Gram-positive bacteria ( Staphylococcus aureus, Staphylococcus epidermidis etc.) in 8 (33.3%). While yeast growth was observed in one patient, no growth in the culture was found in 8 (33.3%) patients . In Doppler ultrasound results; for the Femoral artery, 1 patient was evaluated as monophasic, one patient as biphasic, and 22 patients as triphasic. For the Popliteal artery, 4 patients were assessed as monophasic, 20 patients as triphasic. For the Tibialis anterior artery, 4 patients were monophasic, 2 patients were biphasic, 15 patients were triphasic, and 3 patients had no flow. For the Tibialis posterior artery, 5 patients were monophasic, 2 patients were biphasic, 14 patients were triphasic, and 3 patients had no flow. For the Dorsalis pedis artery, 5 patients were monophasic, one patient was biphasic, 14 patients were triphasic, and 4 patients had no flow. The patients' ABI values were found to have a mean of 0.67 with a standard deviation of 0.08. ABI values ranging from 0.40 to 0.59 were observed in 3 patients, and according to the WIfi classification, ischemia was evaluated as grade 2 for these patients. According to the WIfi classification, all patients were evaluated as high-risk stage-4. The wound status was classified as grade 3 in 1 patient and grade 2 in 23 patients. 99m Tc-MIBI uptake rates of the feet (Figrure 2), distal ankle/proximal ankle (Fig. 3 ), and all extremity parts of the DFU and healthy extremities (Fig. 4 )of the patients were measured separately at the 10th and 30th s. The 99m Tc-MIBI uptake rates of the patients included in the study compared with the healthy extremity over time are summarized in Table 3 . 99m Tc-MIBI uptake images are shown in Figs. 5 , 6 and 7 . In this study, 99m Tc-MIBI uptake rates of patients with poor prognosis were higher at all times than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates (Table 4 ). Table 3 99m Tc-MIBI uptake rates of patients' extremities by time. Variables Anatomical area Time (second) Mean ± SD Median (range) DFUS / HFS Foot 10 12.49 ± 0.48 1.80 (1.06–12.72) DFUS / HFS Foot 30 2.70 ± 0.41 2.00 (1.08–7.50) DFUS/HFS Distal ankle / Proximal ankle 10 1.10 ± 0.12 0.97 (0.25–2.31) DFUS/HFS Distal ankle / Proximal ankle 30 1.16 ± 0.12 0.91 (0.39–2.76) DFUS / HFS Extremity 10 2.26 ± 0.38 1.41 (0.51–7.47) DFUS / HFS Extremity 30 2.01 ± 0.27 1.33 (0.54–4.59) DFUS, diabetic foot ulcereted side; HFS, healthy foot side; SD, standard deviation Table 4 Comparison of 99m Tc-MIBI uptake rates between patient groups. Group 1 (n = 18) Group 2 (n = 6) p -value † Variable Anatomical area Time (second) Mean ± SD Median (range) Mean ± SD Median (range) DFUS / HFS Foot 10 1.85 ± 0.19 1.56 (1.06–3.51) 4.42 ± 1.70 3.06 (1.80–12.70) 0.012 DFUS / HFS Foot 30 2.11 ± 0.35 1.74 (1.08–7.50) 4.45 ± 1.04 4.54 (1.52–7.46) 0.033 DFUS Distal ankle / Proximal ankle 10 1.06 ± 0.13 0.91 (0.40–2.31) 1.23 ± 0.29 1.05 (0.25–2.17) 0.537 DFUS Distal ankle / Proximal ankle 30 1.11 ± 0.14 0.88 (0.49–2.76) 1.31 ± 0.24 1.38 (0.39–2.04) 0.454 DFUS / HFS Extremity 10 2.13 ± 0.43 1.41 (0.51–7.47) 2.66 ± 0.83 1.61 (1.11–5.98) 0.378 DFUS / HFS Extremity 30 1.76 ± 0.28 1.29 (0.54–4.59) 2.74 ± 0.63 2.92 (0.82–4.54) 0.310 DFUS, diabetic foot ulcereted side; HFS, healthy foot side; SD, standard deviation; † Mann-Whitney U test A moderate positive relationship was found between the foot section in the 30th s 99m Tc-MIBI uptake rates and pretreatment CRP levels of the patients who were reoperated. Also, a weak negative relationship was observed between the extremity section in the 10th - and 30th-second 99m Tc-MIBI uptake rates and ALB (CRP: foot section, 10th, r = 0.354, p = 0.089; 30th, r = 0.552, p = 0.005; extremity section, 10th, r = 0.349, p = 0.094; 30th, r = 0.461, p = 0.023; ALB: foot section, 10th, r = − 0.182, p = 0.395; 30th, r = − 0.241, p = 0.256; extremity section, 10th, r = − 0.407, p = − 0.048; 30th, r = − 0.497, p = 0.013). On the contrary, no significant relationship was found between pretreatment sedimentation, WBC count, and 99m Tc-MIBI uptake rates (WBC: foot section, 10th, r = 0.086, p = 0.690; 30th, r = 0.399, p = 0.054; extremity section, 10th, r = 0.239, p = 0.261; 30th, r = 0.343, p = 0.101; sedimentation: foot section, 10th, r = − 0.340, p = 0.104; 30th, r = − 0.382, p = 0.066; extremity section, 10th, r = − 0.251, p = 0.237; 30th, r = − 0.310, p = 0.140). Discussion 99m Tc-MIBI uptake in cells depends on perfusion, viability, and mitochondrial activity [7,8,12,15]. Because of these properties, 99m Tc-MIBI is a radiopharmaceutical agent used in studies of tissue perfusion, viability, and evaluation of peripheral vascular diseases [7,8,14–17,19]. In the literature, 99m Tc-MIBI has been used for perfusion imaging, particularly in LE peripheral vascular diseases [7,8,12,15–17,19]. Although no study has evaluated the level of amputation using 99m Tc-MIBI, particularly in patients with DFU, studies evaluating the perfusion and viability of the musculoskeletal system in patients with DM are also quite limited [7,8,12,15–17] In this study, we tried to determine the amputation level by evaluating the perfusion and vitality of the extremities of patients with DFU using the 99m Tc-MIBI technique, a nuclear imaging method. In this study, the 99m Tc-MIBI uptake rates of patients with poor prognosis were higher at all time points than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates. A moderate positive relationship was found between foot section in the 30th-second 99m Tc-MIBI uptake rate and pretreatment CRP levels of the reoperation group. A weak negative relationship was observed between the extremity section in the 10th- and 30th-second 99m Tc-MIBI uptake rates and ALB. Diabetic foot lesions are a very important health problem because of their high morbidity and mortality rates [1–6]. The mean annual incidence and prevalence of foot ulcers in patients with DM vary between 1–4% and 5–10%, respectively [5]. DM has major microvascular complications including nephropathy, retinopathy, neuropathy, and angiopathy [2,4]. Given the microvascular changes, it can disrupt tissue nutrition and cause organ damage through disorders in coagulation, contractility, permeability, and regeneration mechanisms [8]. Amputation surgery is an important treatment method to remove necrotic tissues from the body, reduce metabolic load, and enable early mobilization of the patients [2,3,7]. The surgical procedure aims to obtain a painless, functional, and long limb stump [1–6]. At this stage, the most appropriate level of amputation must be determined [2–4]. Failure to determine the appropriate level of primary amputation is one of the main causes of reamputation, and reamputation rates of 15–40% have been reported [3,5,6,20]. Accurately determining the amputation level in patients scheduled for amputation because of DFU is a clinical challenge [2–7,9]. No consistent criteria can definitively determine the amputation level before surgery [7,9]. Clinical evaluation, when used alone, is not a reliable indicator of successful recovery of the amputation level [7,9]. The actual amputation level is usually determined by the surgeon during surgery [7]. The level is determined according to intraoperative observations of tissue bleeding and viability of soft tissues and bones [7]. In our study, it was observed that amputations performed at levels with high 99m Tc-MIBI uptake led to higher-level amputations. As 99m Tc-MIBI is directly associated with muscle dysfunction and decreased vitality, we believe it can be used as an imaging modality to determine the level of amputation. Various clinical risk factors for amputation have been identified, and different radiological methods are needed depending on the amputation level [2,5–9,20–22]. Although each method has advantages and disadvantages, determining the exact amputation level is very difficult [5,7,9,20–22]. On the contrary, imaging methods are not consistent enough in routine use in choosing the amputation level [5,7,9,20–22]. Conversely, scintigraphy can be helpful in the diagnosis of inflammation and infection because it is both sensitive and specific [5]. Studies using various radionuclide techniques have provided valuable data for the selection of the optimum amputation level [5,7,9–11,23,24]. Scintigraphy is more likely to determine the most distal amputation level with healthy circulation [7,9,23]. In the absence of radiological findings in diabetic foot wounds, three-phase bone scintigraphy (TPBS) and leukocyte-marked bone scintigraphy are used to determine tissue perfusion and diagnosis of osteomyelitis [5]. In a study conducted to determine the amputation level of diabetic foot, the TPBS method was deemed as a useful method in determining the level [5]. Similarly, [18F] fluoro-2-deoxyglucose PET has been used to distinguish nonviable from salvaged tissues in patients with peripheral vascular disease [9,24]. Although PET uniquely evaluates viability non-invasively, it is expensive and has only limited availability [9]. However, not every scintigraphic technique fully reflects deep tissue perfusion and does not show the lesion extent or distribution [5,7,8,10]. The results of blood flow measurements of the radionuclide may not always be reproducible or reliable [7,8,12,13]. Determination of the viability at the cellular level by these methods is questionable [5,7,8,10,13]. Most accumulate in the extracellular fluid and provide only indirect evidence of tissue viability [7,8,12,13,23]. In addition, these tests are time-consuming [5,7,8,12,13]. However, 99m Tc-MIBI is advantageous with short half-life and allows intravenous injection at higher doses [7,8,12–16]. Given its high energy, its image quality and resolution are superior to other radionuclides [12–16]. 99m Tc-MIBI, a lipophilic cation, enters cells through the negative electric potential difference in the cell membranes and accumulates in the cytoplasm and mitochondria [7,12,13,25]. Cellular uptake and capture of 99m Tc-MIBI are associated not only with regional blood flow but also with mitochondrial metabolic conditions and viability [7,12,13,23]. With 99m Tc-MIBI, infarcted and ischemic tissues in a risky extremity can be detected [7,8,12,13,19,26]. 99m Tc-MIBI is an advantageous agent because of its long-term tissue retention, slow removal from tissues, blood flow-dependent involvement, and better quality imaging [7,8,12,13]. The effective half-life of 99m Tc-MIBI is approximately 5 h, and its physical half-life is approximately 6 h [7,8,12,13]. The fundamental photon energy of gamma emission is 140 keV [7,13]. 99m Tc-MIBI is also superior in terms of toxicity profile because of its low radiation dose [12]. This very low risk of toxicity makes it a suitable tracer for perfusion imaging [12]. Because of these advantages and its high-quality image, many researchers prefer 99m Tc-MIBI in the investigation of peripheral ischemia and perfusion abnormalities in the lower extremities [7,8,12–17,19]. In an experimental study, a clear dividing line between necrotic and normal tissues was demonstrated using 99m Tc-MIBI scan, and these findings were confirmed pathologically [26]. Another study used 99m Tc-MIBI scan to predict surgical outcomes of amputation [7] and reported that 99m Tc-MIBI screening supports its use in selecting the optimal amputation level consistent with subsequent stump healing [7]. Studies using 99m Tc-MIBI in the lower extremities of patients with DM aimed to show a decrease in perfusion reserve in the early period before the development of symptoms and clinical findings in patients with DM [7,8,14–17]. Çelen et al. reported that the mean perfusion reserve of the calf muscles in the DM group was significantly lower than in the control group [8]. Arteriolar dilatation, capillary permeability, and neuropathy are important factors in perfusion reserve [7,8,14–17]. To determine the amputation level in our study, while evaluating the extremity perfusion of patients with DFU, the healthy contralateral LEs of the patients were examined under the same conditions and simultaneously and used as the control group. The most important side effect of 99m Tc-MIBI is post-injection allergic reactions; however, they are rarely seen [27]. Overall, 99m Tc-MIBI is less radiotoxic than other radiopharmaceuticals because of its lower degree of nuclear localization and unrepaired double-stranded DNA breakage [28]. Most side effects are very temporary and rarely require intervention [12]. In our study, no complications were observed during the follow-up period. This study has some limitations. First, the relatively small number of patients was evaluated. Since this study was conducted during the COVID-19 pandemic, some patients were lost during follow-up and were excluded from the study. Second, we had problems with the supply of radionuclides, which affected the number of our patients. Finally, the follow-up period was relatively short. Further prospective studies may be planned to evaluate this technique in larger patient populations with longer follow-up. Conclusions Radionuclide angiography has not yet been accepted as a routine method for determining the appropriate amputation level. Given its costs, its routine use is limited. However, 99m Tc-MIBI technique may contribute to determining the amputation level and reducing the number of additional amputation attempts, considering the condition of the patients. With 99m Tc-MIBI, physicians’ awareness about the amputation level in patients with DFU must be improved. Information gathered from 99m Tc-MIBI is likely to guide the method, course, and duration of treatment. Declarations The article has not been published anywhere before. Funding : This study was not funded Conflicts of interest : There is no conflict of interest Ethics approval: Local ethic committee approve was taken from the Kayseri City Education and Research Hospital. Consent to participate and Consent for publication: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Author Contribution ME designed the study. ME, HG and SK carried out the imaging and data collection part of the study in nuclear medicine and clinical areas. ME, AEG and FO performed the writing and statistical part.All authors reviewed the manuscript. References Hoogeveen RC, Dorresteijn JAN, Kriegsman DMW, Valk GD. Complex interventions for preventing diabetic foot ulceration. Cochrane Database Syst Rev. 2015;2015:CD007610. Lee DW, Kwak SH, Kim JH, Choi HJ. Prediction of diabetic foot amputation using newly revised DIRECT coding system: Comparison of accuracy with that of five existing classification systems. Int Wound J. 2023;20:359–71. Gazzaruso C, Gallotti P, Pujia A, Montalcini T, Giustina A, Coppola A. Predictors of healing, ulcer recurrence and persistence, amputation and mortality in type 2 diabetic patients with diabetic foot: a 10-year retrospective cohort study. Endocrine. 2021;71:59–68. Jeon B-J, Choi HJ, Kang JS, Tak MS, Park ES. Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation. Int Wound J. 2017;14:537–45. Baykal YB, Yaman E, Burc H, Yorgancigil H, Atay T, Yildiz M. Is scintigraphy a guideline method in determining amputation levels in diabetic foot? J Am Podiatr Med Assoc. 2014;104:227–32. Ozan F, Gürbüz K, Çelik I, Bestepe Dursun Z, Uzun E. Evaluation of major and minor lower extremity amputation in diabetic foot patients. Turk J Med Sci. 2017;47:1109–16. Sarikaya A, Top H, Aygit AC, Benlier E, Unal Y. Predictive value of 99mTc-sestamibi scintigraphy for healing of extremity amputation. Eur J Nucl Med Mol Imaging. 2006;33:1500–7. Celen YZ, Zincirkeser S, Akdemir I, Yilmaz M. Investigation of perfusion reserve using 99Tc(m)-MIBI in the lower limbs of diabetic patients. Nucl Med Commun. 2000;21:817–22. Lauri C, Leone A, Cavallini M, Signore A, Giurato L, Uccioli L. Diabetic Foot Infections: The Diagnostic Challenges. J Clin Med. 2020;9:1779. Asli IN, Javadi H, Seddigh H, Mogharrabi M, Hooman A, Ansari M, et al. The diagnostic value of (99m)Tc-IgG scintigraphy in the diabetic foot and comparison with (99m)Tc-MDP scintigraphy. J Nucl Med Technol. 2011;39:226–30. Malone JM, Leal JM, Moore WS, Henry RE, Daly MJ, Patton DD, et al. The “gold standard” for amputation level selection" xenon-133 clearance. J Surg Res. 1981;30:449–55. Rizk TH, Nagalli S. Technetium 99m Sestamibi. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Feb 3]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK553148/ Top H, Sarikaya A, Aygit AC, Benlier E, Kiyak M. Review of monitoring free muscle flap transfers in reconstructive surgery: role of 99mTc sestamibi scintigraphy. Nucl Med Commun. 2006;27:91–8. Manevska N, Stojanoski S, Pop Gjorceva D, Todorovska L, Vavlukis M, Majstorov V. Tissue-muscle perfusion assessed by one day 99mTc-MIBI rest-dipyridamol scintigraphy in non-diabetic and diabetic patients. Rev Esp Med Nucl Imagen Mol (Engl Ed). 2018;37:141–5. Nemcova A, Jirkovska A, Dubsky M, Bem R, Fejfarova V, Woskova V, et al. Perfusion scintigraphy in the assessment of autologous cell therapy in diabetic patients with critical limb ischemia. Physiol Res. 2018;67:583–9. Li Y, Li Q, Liang S, Liang X, Zhou W, He H, et al. A novel use of hill function and utility of 99mTc-MIBI scintigraphy to detect earlier lower extremity microvascular perfusion in patients with type 2 diabetes. Medicine (Baltimore). 2017;96:e8038. Zhang Q, Liu X, Li Q, Liu Y, He H, Wang K, et al. Quantitative model for assessment of lower-extremity perfusion in patients with diabetes. Med Phys. 2023;50:3019–26. Cerqueira L de O, Duarte EG, Barros AL de S, Cerqueira JR, de Araújo WJB. WIfI classification: the Society for Vascular Surgery lower extremity threatened limb classification system, a literature review. J Vasc Bras. 19:e20190070. Aygit AC, Sarikaya A. Imaging of frostbite injury by technetium-99m-sestamibi scintigraphy: a case report. Foot Ankle Int. 2002;23:56–9. Adiyeke L, Karagoz B. Analysis of Doppler ultrasonography and computer tomography angiography for predicting amputation level and re-amputation rate. North Clin Istanb. 2022;9:401–7. Jbara M, Gokli A, Beshai S, Lesser ML, Hanna S, Lin C, et al. Does obtaining an initial magnetic resonance imaging decrease the reamputation rates in the diabetic foot? Diabet Foot Ankle. 2016;7:31240. Chou Y-Y, Hou C-C, Wu C-W, Huang D-W, Tsai S-L, Liu T-H, et al. Risk factors that predict major amputations and amputation time intervals for hospitalised diabetic patients with foot complications. Int Wound J. 2022;19:1329–38. Bhatnagar A, Sarker BB, Sawroop K, Chopra MK, Sinha N, Kashyap R. Diagnosis, characterisation and evaluation of treatment response of frostbite using pertechnetate scintigraphy: a prospective study. Eur J Nucl Med Mol Imaging. 2002;29:170–5. Smith GT, Wilson TS, Hunter K, Besozzi MC, Hubner KF, Reath DB, et al. Assessment of skeletal muscle viability by PET. J Nucl Med. 1995;36:1408–14. Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. Circulation. 1990;82:1826–38. Sarikaya I, Aygit AC, Candan L, Sarikaya A, Türkyilmaz M, Berkarda S. Assessment of tissue viability after frostbite injury by technetium-99m-sestamibi scintigraphy in an experimental rabbit model. Eur J Nucl Med. 2000;27:41–5. Hesse B, Vinberg N, Mosbech H. Exanthema after a stress Tc-99m sestamibi study: continue with a rest sestamibi study? Clin Physiol Funct Imaging. 2011;31:246–8. Maucksch U, Runge R, Wunderlich G, Freudenberg R, Naumann A, Kotzerke J. Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI. Int J Radiat Biol. 2016;92:698–706. Additional Declarations No competing interests reported. Supplementary Files orcd.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4165516","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":285162345,"identity":"56cb855b-62ec-4ea2-a944-bcf757847571","order_by":0,"name":"mehmet ekici","email":"data:image/png;base64,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","orcid":"","institution":"Kayseri state hospital","correspondingAuthor":true,"prefix":"","firstName":"mehmet","middleName":"","lastName":"ekici","suffix":""},{"id":285162347,"identity":"c3b2a383-2116-4a15-b997-6892880de390","order_by":1,"name":"ali eray günay","email":"","orcid":"","institution":"Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"ali","middleName":"eray","lastName":"günay","suffix":""},{"id":285162351,"identity":"0749119f-ec0d-4d73-b25e-f3e554c3b9df","order_by":2,"name":"seyhan karaçavuş","email":"","orcid":"","institution":"Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"seyhan","middleName":"","lastName":"karaçavuş","suffix":""},{"id":285162353,"identity":"8302d2aa-54b0-41f9-9e77-4c58811eb472","order_by":3,"name":"hümeyra gençer","email":"","orcid":"","institution":"Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"hümeyra","middleName":"","lastName":"gençer","suffix":""},{"id":285162356,"identity":"0dab5451-96a8-49d1-84cf-ef39b6a20612","order_by":4,"name":"fırat ozan","email":"","orcid":"","institution":"Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"fırat","middleName":"","lastName":"ozan","suffix":""}],"badges":[],"createdAt":"2024-03-25 20:29:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4165516/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4165516/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53955720,"identity":"deebd2be-d76b-45d9-b3b1-838c8bc11446","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":460246,"visible":true,"origin":"","legend":"\u003cp\u003eSPECT/CT image (right foot: Diabetic Foot Ulcer Side, left foot: Healty Foot Side)\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/6a77c066b9c28345ec41a243.jpeg"},{"id":53955719,"identity":"c3123789-3893-4b21-8d99-8ee0cc64985d","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75904,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of the feet (green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/294794c47b394c3e01ddb5a3.jpeg"},{"id":53955724,"identity":"e4fc95c4-bbe8-4d61-84bf-4bd9da136437","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":52803,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of distal ankle/proximal ankle\u003c/p\u003e\n\u003cp\u003e(green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/cc99fecdac3ef314b07d5d5e.jpeg"},{"id":53955725,"identity":"0b18e4a1-8893-4d0f-843b-05e76fbf25d0","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":53022,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of legs (green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/688ce84f0e8886238679ab9f.jpeg"},{"id":53955726,"identity":"076e7d95-66f4-4599-b0d8-263ea49b1ab3","added_by":"auto","created_at":"2024-04-02 17:09:27","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":207136,"visible":true,"origin":"","legend":"\u003cp\u003eSecond-by-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake and its graphs for feet. (green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/918fbf14e17f0e30f25604d6.jpeg"},{"id":53955722,"identity":"06fb84dd-0fe4-441f-98c4-ab867a5244ef","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":104849,"visible":true,"origin":"","legend":"\u003cp\u003eSecond-by-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake and its graphs for distal\u003c/p\u003e\n\u003cp\u003eankle/proximal ankle. (green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/572b215ae2a8333df9791864.jpeg"},{"id":53955723,"identity":"4206690a-b700-47c6-ad8c-f6ed7dbadc50","added_by":"auto","created_at":"2024-04-02 17:09:26","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":111719,"visible":true,"origin":"","legend":"\u003cp\u003eSecond-by-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake and its graphs for legs. (green; HFS, red; DFUS)\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/5f442ef2457461bc105c71d0.jpeg"},{"id":56430736,"identity":"ce6a7679-3bc2-4a55-b6a0-4e987268a0b0","added_by":"auto","created_at":"2024-05-14 06:08:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":929853,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/f5f89d67-99bf-470d-bc54-f611bc0cfbeb.pdf"},{"id":53956167,"identity":"3acee986-dfd9-4bb0-8332-865043526c26","added_by":"auto","created_at":"2024-04-02 17:17:26","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13156,"visible":true,"origin":"","legend":"","description":"","filename":"orcd.docx","url":"https://assets-eu.researchsquare.com/files/rs-4165516/v1/26991ce389c9cbeae5759097.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical value of Tc-99m MIBI scintigraphy for the level of lower limb amputation in patients with diabetic foot ulcers","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiabetes mellitus (DM) is an important public health problem with an increasing incidence worldwide [1]. Even a small DFU can compromise the viability of the entire foot [1,2]. The risk of death within 5 years for a patient with DFU is 2.5 times higher than that for a patient with DM without a foot ulcer [1,3].\u003c/p\u003e \u003cp\u003eThe worst possible potential outcome of DFU, other than death, is lower-extremity amputation (LEA) [1,4]. Approximately 20% of patients with DFU require LEA [1\u0026ndash;3,5]. DFU-related amputations constitute 40%\u0026ndash;[85% of nontraumatic amputations [1,3\u0026ndash;6]. Once amputated, the incidence of a second amputation in the contralateral limb reaches 50% within 2 years [3,5,6]. Amputation negatively affects the quality of life of patients with DFU Predicting the level of DFU-related amputation can reduce amputation rates by observation and prophylactic action for the high-risk groups [1\u0026ndash;4]. Many studies have explored efforts to prevent foot amputation and determine risk factors associated with amputation [1\u0026ndash;7]. Clinical history and physical examination, transcutaneous oxygen pressure measurement, Doppler ultrasonography (USG), computed tomography (CT), contrasted CT angiography, and venography, magnetic resonance imaging (MRI), MRI angiography, carbon dioxide angiography, and lower extremity (LE) duplex scanning are the methods frequently used in the evaluation of peripheral vascular disease [2\u0026ndash;9]. In addition, various nuclear medicine techniques are also used [5,7\u0026ndash;14]. Technetium 99m monomer methoxy isobutyl isonitrile (\u003csup\u003e99m\u003c/sup\u003eTc-MIBI), also known as \u003csup\u003e99m\u003c/sup\u003eTc sestamibi, is a radiopharmaceutical used to evaluate pathology in heart, breast, and parathyroid [7,8,12\u0026ndash;16]. 99mTc-MIBI is part of a class of radioactive diagnostic agents characterised as lipophilic cationic radiotracers.[12\u0026ndash;14].\u003csup\u003e99m\u003c/sup\u003eTc-MIBI is localized to intramitochondrial anionic proteins in cells [8,12\u0026ndash;14]. Cellular uptake is proportional to regional blood flow, mitochondrial activity, and cellular viability [8]. \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is not organ-specific and is inversely correlated with mitochondrial function [8,12].\u003c/p\u003e \u003cp\u003eThere are studies evaluating musculoskeletal system perfusion and viability using 99mTc-MIBI in patients with DM [7,15] and both with and without DM [8,14,16,17]..\u003c/p\u003e \u003cp\u003eWith this study, we aimed to determine the predictability of the amputation level to reduce the risk of amputation and develop better treatment strategies in patients with DFU. For this purpose, we evaluated the perfusion and viability of skeletal muscles using \u003csup\u003e99m\u003c/sup\u003eTc-MIBI in patients with DFU and tried to determine the relationship between the uptake rates recorded with \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scintigraphy and amputation level and reamputation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 35 patients hospitalized for DFU between January 2020 and March 2020 in the Diabetic Foot Wound Clinic of our hospital were included in the study and evaluated prospectively. At the end of the first year, 11 patients who were lost to follow-up because of the COVID-19 pandemic were excluded from the study, and the study was completed with 24 feet (19 men, 5 women; 12 right sides, 12 left sides; mean age, 63.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3 years; range, 42\u0026ndash;86 years) of 24 patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eAs a result of treatment that started with the hospitalization, patients whose DFUs healed and did not need surgical intervention were determined as group 1, and patients whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention were determined as group 2. Group 2 consisted of patients who received antibiotherapy for the isolated agent, received anticoagulant therapy, did not recover despite repeated debridements, daily dressings and supportive treatments (such as HBO) and needed high-level amputation.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows: patients with diabetic foot ulcer, no previous surgical procedure, diagnosis of type 2 DM, age\u0026thinsp;\u0026ge;\u0026thinsp;18 years. The exclusion criteria were as follows: type 1 DM, DFU in both lower extremities, pregnancy, or lactation patients, a history of malignancy, a history of sepsis, non DM ischemic peripheral artery disease, and any known history of allergy or a history of hypersensitivity to proteins.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData measurement\u003c/h2\u003e \u003cp\u003ePatients\u0026rsquo; age, sex, smoking history, DM duration, DFU side, Wagner classification, previous amputation history, peripheral arterial disease (PAD), laboratory values, microbiologic culture results, and medical comorbidities were collected. In the laboratory evaluation, hemoglobin (Hb), white blood cell (WBC), plasma albumin (ALB), glycosylated hemoglobin A1c (HbA1c), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), eGFR, creatinin, Ankle Brachial Index (ABI), peak systolic velocitieslevels were measured.\u003c/p\u003e \u003cp\u003eThe Doppler ultrasound results for Arteria Femoralis, Arteria Poplitealis, Arteia Tibialis Posterior (ATP), Arteria Doraslis Pedis (ADP), and Arteria Tibialis Anterior (ATA) were recorded as triphasic, biphasic, and monophasic.\u003c/p\u003e \u003cp\u003eLE radiographs and MRI were used to evaluate the presence of neuropathic arthropathy (Charcot arthropathy) or osteomyelitis. LE USG was used to evaluate PAD.\u003c/p\u003e \u003cp\u003eThe SVS classification system, which emerged in 2013 and was formally introduced in an SVS publication in 2014, addresses three critical factors contributing to the risk of limb amputation: wound, ischemia, and foot infection. The SVS WIfI classification assigns a 4-grade scale to each parameter, ranging from 0 to 3, with 0 indicating absence, 1 denoting mild, 2 indicating moderate, and 3 representing severe [18].\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cb\u003e99m\u003c/b\u003e \u003c/sup\u003e \u003cb\u003eTc-MIBI scintigraphy\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDouble-headed single-photon emission tomography/computed tomography (SPECT/CT; Mediso AnyScan\u0026reg;SC) was used for imaging. Tetrakis (2-methoxyisobutyl isonitrile) copper (I) tetrafluoroborate (1.0 mg, MON.MIBI KIT; Eczacıbaşı Monrol) was labeled with \u003csup\u003e99m\u003c/sup\u003eTc radionuclide obtained by daily milking from the Mo-Tc generator.\u003c/p\u003e \u003cp\u003eAfter the patients were placed in the appropriate position, the detectors using the low-energy high-resolution collimator were positioned at 180\u0026deg;, and the foot area was focused in the anterior\u0026ndash;posterior positions. After the parenteral administration of 20 mCi \u003csup\u003e99m\u003c/sup\u003eTc-MIBI, dynamic imaging was started. Data were collected from the anterior and posterior projections in a 15-s 30-frame, 128 \u0026times; 128 matrix, without using a zoom factor. After dynamic imaging, 300 s of static imaging was performed in anterior\u0026ndash;posterior positions. Subsequently, SPECT/CT images were acquired without changing the patient\u0026rsquo;s position (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe obtained images were analyzed using the Interview 2.0 program on the workstation connected to the Mediso AnyScan\u0026reg;SC gamma camera. An intact extremity was taken as a reference for evaluation. Relevant areas of the extremity with DFU and the contralateral healthy extremity were taken and proportioned. The peak activity values at the 10th and 30th seconds were taken as a basis. This process was performed separately for anterior and posterior imaging, and the arithmetic mean of the values was calculated. Time\u0026ndash;activity curves were obtained for all analyses.\u003c/p\u003e \u003cp\u003eWith \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scintigraphy, the \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of the foot of the diabetic ulcerated extremity side/foot of healthy extremity side, distal ankle of diabetic ulcerated extremity side/proximal ankle of diabetic ulcerated extremity side, and extremity of the diabetic ulcerated side/extremity of healthy side were measured at 10 and 30 s, respectively. Two nuclear medicine consultants unaware of the data evaluated the scintigraphic studies and reached the final impression by consensus.\u003c/p\u003e \u003cp\u003eThe uptake rates of \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scintigraphy at the 10th and 30th seconds will be compared between Group 1 and Group 2. The relationship between these rates and the need for upper-level amputation will be demonstrated with \u003csup\u003e99m\u003c/sup\u003eTc-MIBI.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEthical issues\u003c/h2\u003e \u003cp\u003e The study protocol was approved by the Erciyes University Faculty of Medicine, Clinical Research Ethics Committee (Approval date/no. January 16, 2020/30) and conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analyses were conducted with IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, USA). Percentages and standard deviations were determined for categorical data and continuous variables, and the Shapiro\u0026ndash;Wilk test, and histograms were used to evaluate data distribution. Pearson\u0026rsquo;s chi-square test compared categorical data between the groups. After the difference between repeated measurements was analyzed with the Friedman test, pairwise comparisons were made with the Dunn test. The Mann\u0026ndash;Whitney U test was used to examine the difference between nondependent groups. The relationship between laboratory results and \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake results was evaluated by the Spearman correlation analysis. A value of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean hospital stay was 14.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 (range, 3\u0026ndash;45) days. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the baseline characteristics of the patients. Before the patients' clinical admissions, the average wound duration was calculated to be 3.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03 months. Moreover, 6 (25%) patients required a repeat surgical procedure. Of the 3 patients who underwent toe amputation, 2 underwent transmetatarsal amputation and one patient underwent below-knee amputation. One patient who underwent transmetatarsal amputation underwent below-knee amputation. Two patients who underwent below-knee amputation underwent below-knee amputation.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; demographic characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n\u003c/p\u003e \u003cp\u003eWomen\u003c/p\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.634\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003cp\u003ePresent\u003c/p\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.649\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of DM (yr), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.494\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of comorbidities, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.353\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide of involvement, n\u003c/p\u003e \u003cp\u003eRight\u003c/p\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD, standard deviation; DM, diabetes mellitus; HbA1c, glycated hemoglobin; \u003csup\u003ea\u003c/sup\u003e Mann-Whitney U test; \u003csup\u003eb\u003c/sup\u003e Chi-square test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhile the patients\u0026rsquo; baseline WBC, ESR, and CRP levels decreased over time, the ALB level increased. Laboratory values at the end of the follow-up were significantly different from the initial values (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory results of the patients during follow-up.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAT Month 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAT Month 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAT Month 6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC [10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L] median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.6 (4.3\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7 (3.9\u0026ndash;18.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5 (4\u0026ndash;17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.5 (4.1\u0026ndash;22) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR [mm/hr] median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58.5 (4\u0026ndash;140)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (4\u0026ndash;138)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (2\u0026ndash;198)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15 (2.8\u0026ndash;140)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP [mg/L] median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79.35 (2\u0026ndash;322)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.4 (0.7\u0026ndash;170)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.85 (1.1\u0026ndash;154)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.95 (0.9\u0026ndash;267)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB [g/L] median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34.2 (27\u0026ndash;44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (25\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (23\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e38.5 (18\u0026ndash;47)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eBT, before treatment; AT, after treatment; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; \u003cb\u003eALB\u003c/b\u003e, albumin; \u003csup\u003e\u0026dagger;\u003c/sup\u003e Friedman test; \u003csup\u003e*\u003c/sup\u003e The difference compared to BT was statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen the mean CRP and ALB levels of the groups were compared before the treatment, the CRP level in the reoperated group was significantly higher and the ALB level was low (ALB, 35.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32 (range, 28\u0026ndash;44) vs. 32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53 (range, 27\u0026ndash;37), respectively, p\u0026thinsp;=\u0026thinsp;0.224; CRP, 86.04\u0026thinsp;\u0026plusmn;\u0026thinsp;21.87 (range, 2\u0026ndash;232) vs. 144.43\u0026thinsp;\u0026plusmn;\u0026thinsp;27.54 (range, 107\u0026ndash;281), respectively, p\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003ePatients' average eGFR values during clinical admissions were calculated as 53.12\u0026thinsp;\u0026plusmn;\u0026thinsp;13.53 ml/min. The mean creatinine level was 1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35 mg/dL. The average hemoglobin level was measured at 11.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73 g/dL.\u003c/p\u003e \u003cp\u003eIn the deep tissue cultures of the patients, Gram-negative bacteria \u003cem\u003e(Escherichia coli, Ps\u0026ouml;domonas aeruginosa\u003c/em\u003e etc.) were detected in 7 (29.1%) patients and Gram-positive bacteria (\u003cem\u003eStaphylococcus aureus, Staphylococcus epidermidis\u003c/em\u003e etc.) in 8 (33.3%). While yeast growth was observed in one patient, no growth in the culture was found in 8 (33.3%) patients .\u003c/p\u003e \u003cp\u003eIn Doppler ultrasound results; for the Femoral artery, 1 patient was evaluated as monophasic, one patient as biphasic, and 22 patients as triphasic. For the Popliteal artery, 4 patients were assessed as monophasic, 20 patients as triphasic. For the Tibialis anterior artery, 4 patients were monophasic, 2 patients were biphasic, 15 patients were triphasic, and 3 patients had no flow. For the Tibialis posterior artery, 5 patients were monophasic, 2 patients were biphasic, 14 patients were triphasic, and 3 patients had no flow. For the Dorsalis pedis artery, 5 patients were monophasic, one patient was biphasic, 14 patients were triphasic, and 4 patients had no flow.\u003c/p\u003e \u003cp\u003eThe patients' ABI values were found to have a mean of 0.67 with a standard deviation of 0.08. ABI values ranging from 0.40 to 0.59 were observed in 3 patients, and according to the WIfi classification, ischemia was evaluated as grade 2 for these patients.\u003c/p\u003e \u003cp\u003eAccording to the WIfi classification, all patients were evaluated as high-risk stage-4. The wound status was classified as grade 3 in 1 patient and grade 2 in 23 patients.\u003c/p\u003e \u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of the feet (Figrure 2), distal ankle/proximal ankle (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), and all extremity parts of the DFU and healthy extremities (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)of the patients were measured separately at the 10th and 30th s. The \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of the patients included in the study compared with the healthy extremity over time are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake images are shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e and \u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. In this study, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of patients with poor prognosis were higher at all times than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of patients' extremities by time.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnatomical area\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003cp\u003e(second)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFoot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.80 (1.06\u0026ndash;12.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFoot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.00 (1.08\u0026ndash;7.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS/HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDistal ankle / Proximal ankle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.97 (0.25\u0026ndash;2.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS/HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDistal ankle / Proximal ankle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.91 (0.39\u0026ndash;2.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.41 (0.51\u0026ndash;7.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.33 (0.54\u0026ndash;4.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDFUS, diabetic foot ulcereted side; HFS, healthy foot side; SD, \u003cb\u003estandard deviation\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates between patient groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnatomical area\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime (second)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFoot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.56\u003c/p\u003e \u003cp\u003e(1.06\u0026ndash;3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e4.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.06\u003c/p\u003e \u003cp\u003e(1.80\u0026ndash;12.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFoot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.74\u003c/p\u003e \u003cp\u003e(1.08\u0026ndash;7.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e4.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.54\u003c/p\u003e \u003cp\u003e(1.52\u0026ndash;7.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDistal ankle / Proximal ankle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003cp\u003e(0.40\u0026ndash;2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003cp\u003e(0.25\u0026ndash;2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDistal ankle / Proximal ankle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003cp\u003e(0.49\u0026ndash;2.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003cp\u003e(0.39\u0026ndash;2.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.454\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.41\u003c/p\u003e \u003cp\u003e(0.51\u0026ndash;7.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e2.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.61\u003c/p\u003e \u003cp\u003e(1.11\u0026ndash;5.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.378\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDFUS / HFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtremity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003cp\u003e(0.54\u0026ndash;4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.92\u003c/p\u003e \u003cp\u003e(0.82\u0026ndash;4.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.310\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eDFUS, diabetic foot ulcereted side; HFS, healthy foot side; SD, \u003cb\u003estandard deviation;\u003c/b\u003e \u003csup\u003e\u0026dagger;\u003c/sup\u003e Mann-Whitney U test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA moderate positive relationship was found between the foot section in the 30th s \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates and pretreatment CRP levels of the patients who were reoperated. Also, a weak negative relationship was observed between the extremity section in the 10th - and 30th-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates and ALB (CRP: foot section, 10th, r\u0026thinsp;=\u0026thinsp;0.354, p\u0026thinsp;=\u0026thinsp;0.089; 30th, r\u0026thinsp;=\u0026thinsp;0.552, p\u0026thinsp;=\u0026thinsp;0.005; extremity section, 10th, r\u0026thinsp;=\u0026thinsp;0.349, p\u0026thinsp;=\u0026thinsp;0.094; 30th, r\u0026thinsp;=\u0026thinsp;0.461, p\u0026thinsp;=\u0026thinsp;0.023; ALB: foot section, 10th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.182, p\u0026thinsp;=\u0026thinsp;0.395; 30th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.241, p\u0026thinsp;=\u0026thinsp;0.256; extremity section, 10th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.407, p\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.048; 30th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.497, p\u0026thinsp;=\u0026thinsp;0.013). On the contrary, no significant relationship was found between pretreatment sedimentation, WBC count, and \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates (WBC: foot section, 10th, r\u0026thinsp;=\u0026thinsp;0.086, p\u0026thinsp;=\u0026thinsp;0.690; 30th, r\u0026thinsp;=\u0026thinsp;0.399, p\u0026thinsp;=\u0026thinsp;0.054; extremity section, 10th, r\u0026thinsp;=\u0026thinsp;0.239, p\u0026thinsp;=\u0026thinsp;0.261; 30th, r\u0026thinsp;=\u0026thinsp;0.343, p\u0026thinsp;=\u0026thinsp;0.101; sedimentation: foot section, 10th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.340, p\u0026thinsp;=\u0026thinsp;0.104; 30th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.382, p\u0026thinsp;=\u0026thinsp;0.066; extremity section, 10th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.251, p\u0026thinsp;=\u0026thinsp;0.237; 30th, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.310, p\u0026thinsp;=\u0026thinsp;0.140).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake in cells depends on perfusion, viability, and mitochondrial activity [7,8,12,15]. Because of these properties, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is a radiopharmaceutical agent used in studies of tissue perfusion, viability, and evaluation of peripheral vascular diseases [7,8,14\u0026ndash;17,19]. In the literature, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI has been used for perfusion imaging, particularly in LE peripheral vascular diseases [7,8,12,15\u0026ndash;17,19]. Although no study has evaluated the level of amputation using \u003csup\u003e99m\u003c/sup\u003eTc-MIBI, particularly in patients with DFU, studies evaluating the perfusion and viability of the musculoskeletal system in patients with DM are also quite limited [7,8,12,15\u0026ndash;17] In this study, we tried to determine the amputation level by evaluating the perfusion and vitality of the extremities of patients with DFU using the \u003csup\u003e99m\u003c/sup\u003eTc-MIBI technique, a nuclear imaging method. In this study, the \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of patients with poor prognosis were higher at all time points than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates. A moderate positive relationship was found between foot section in the 30th-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rate and pretreatment CRP levels of the reoperation group. A weak negative relationship was observed between the extremity section in the 10th- and 30th-second \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates and ALB.\u003c/p\u003e \u003cp\u003eDiabetic foot lesions are a very important health problem because of their high morbidity and mortality rates [1\u0026ndash;6]. The mean annual incidence and prevalence of foot ulcers in patients with DM vary between 1\u0026ndash;4% and 5\u0026ndash;10%, respectively [5]. DM has major microvascular complications including nephropathy, retinopathy, neuropathy, and angiopathy [2,4]. Given the microvascular changes, it can disrupt tissue nutrition and cause organ damage through disorders in coagulation, contractility, permeability, and regeneration mechanisms [8].\u003c/p\u003e \u003cp\u003eAmputation surgery is an important treatment method to remove necrotic tissues from the body, reduce metabolic load, and enable early mobilization of the patients [2,3,7]. The surgical procedure aims to obtain a painless, functional, and long limb stump [1\u0026ndash;6]. At this stage, the most appropriate level of amputation must be determined [2\u0026ndash;4]. Failure to determine the appropriate level of primary amputation is one of the main causes of reamputation, and reamputation rates of 15\u0026ndash;40% have been reported [3,5,6,20].\u003c/p\u003e \u003cp\u003eAccurately determining the amputation level in patients scheduled for amputation because of DFU is a clinical challenge [2\u0026ndash;7,9]. No consistent criteria can definitively determine the amputation level before surgery [7,9]. Clinical evaluation, when used alone, is not a reliable indicator of successful recovery of the amputation level [7,9]. The actual amputation level is usually determined by the surgeon during surgery [7]. The level is determined according to intraoperative observations of tissue bleeding and viability of soft tissues and bones [7]. In our study, it was observed that amputations performed at levels with high \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake led to higher-level amputations. As \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is directly associated with muscle dysfunction and decreased vitality, we believe it can be used as an imaging modality to determine the level of amputation.\u003c/p\u003e \u003cp\u003eVarious clinical risk factors for amputation have been identified, and different radiological methods are needed depending on the amputation level [2,5\u0026ndash;9,20\u0026ndash;22]. Although each method has advantages and disadvantages, determining the exact amputation level is very difficult [5,7,9,20\u0026ndash;22]. On the contrary, imaging methods are not consistent enough in routine use in choosing the amputation level [5,7,9,20\u0026ndash;22].\u003c/p\u003e \u003cp\u003eConversely, scintigraphy can be helpful in the diagnosis of inflammation and infection because it is both sensitive and specific [5]. Studies using various radionuclide techniques have provided valuable data for the selection of the optimum amputation level [5,7,9\u0026ndash;11,23,24]. Scintigraphy is more likely to determine the most distal amputation level with healthy circulation [7,9,23].\u003c/p\u003e \u003cp\u003eIn the absence of radiological findings in diabetic foot wounds, three-phase bone scintigraphy (TPBS) and leukocyte-marked bone scintigraphy are used to determine tissue perfusion and diagnosis of osteomyelitis [5]. In a study conducted to determine the amputation level of diabetic foot, the TPBS method was deemed as a useful method in determining the level [5]. Similarly, [18F] fluoro-2-deoxyglucose PET has been used to distinguish nonviable from salvaged tissues in patients with peripheral vascular disease [9,24]. Although PET uniquely evaluates viability non-invasively, it is expensive and has only limited availability [9].\u003c/p\u003e \u003cp\u003eHowever, not every scintigraphic technique fully reflects deep tissue perfusion and does not show the lesion extent or distribution [5,7,8,10]. The results of blood flow measurements of the radionuclide may not always be reproducible or reliable [7,8,12,13]. Determination of the viability at the cellular level by these methods is questionable [5,7,8,10,13]. Most accumulate in the extracellular fluid and provide only indirect evidence of tissue viability [7,8,12,13,23]. In addition, these tests are time-consuming [5,7,8,12,13].\u003c/p\u003e \u003cp\u003eHowever, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is advantageous with short half-life and allows intravenous injection at higher doses [7,8,12\u0026ndash;16]. Given its high energy, its image quality and resolution are superior to other radionuclides [12\u0026ndash;16]. \u003csup\u003e99m\u003c/sup\u003eTc-MIBI, a lipophilic cation, enters cells through the negative electric potential difference in the cell membranes and accumulates in the cytoplasm and mitochondria [7,12,13,25]. Cellular uptake and capture of \u003csup\u003e99m\u003c/sup\u003eTc-MIBI are associated not only with regional blood flow but also with mitochondrial metabolic conditions and viability [7,12,13,23]. With \u003csup\u003e99m\u003c/sup\u003eTc-MIBI, infarcted and ischemic tissues in a risky extremity can be detected [7,8,12,13,19,26].\u003c/p\u003e \u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is an advantageous agent because of its long-term tissue retention, slow removal from tissues, blood flow-dependent involvement, and better quality imaging [7,8,12,13]. The effective half-life of \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is approximately 5 h, and its physical half-life is approximately 6 h [7,8,12,13]. The fundamental photon energy of gamma emission is 140 keV [7,13]. \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is also superior in terms of toxicity profile because of its low radiation dose [12]. This very low risk of toxicity makes it a suitable tracer for perfusion imaging [12].\u003c/p\u003e \u003cp\u003eBecause of these advantages and its high-quality image, many researchers prefer \u003csup\u003e99m\u003c/sup\u003eTc-MIBI in the investigation of peripheral ischemia and perfusion abnormalities in the lower extremities [7,8,12\u0026ndash;17,19]. In an experimental study, a clear dividing line between necrotic and normal tissues was demonstrated using \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scan, and these findings were confirmed pathologically [26]. Another study used \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scan to predict surgical outcomes of amputation [7] and reported that \u003csup\u003e99m\u003c/sup\u003eTc-MIBI screening supports its use in selecting the optimal amputation level consistent with subsequent stump healing [7].\u003c/p\u003e \u003cp\u003eStudies using \u003csup\u003e99m\u003c/sup\u003eTc-MIBI in the lower extremities of patients with DM aimed to show a decrease in perfusion reserve in the early period before the development of symptoms and clinical findings in patients with DM [7,8,14\u0026ndash;17]. \u0026Ccedil;elen et al. reported that the mean perfusion reserve of the calf muscles in the DM group was significantly lower than in the control group [8]. Arteriolar dilatation, capillary permeability, and neuropathy are important factors in perfusion reserve [7,8,14\u0026ndash;17]. To determine the amputation level in our study, while evaluating the extremity perfusion of patients with DFU, the healthy contralateral LEs of the patients were examined under the same conditions and simultaneously and used as the control group.\u003c/p\u003e \u003cp\u003eThe most important side effect of \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is post-injection allergic reactions; however, they are rarely seen [27]. Overall, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is less radiotoxic than other radiopharmaceuticals because of its lower degree of nuclear localization and unrepaired double-stranded DNA breakage [28]. Most side effects are very temporary and rarely require intervention [12]. In our study, no complications were observed during the follow-up period.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, the relatively small number of patients was evaluated. Since this study was conducted during the COVID-19 pandemic, some patients were lost during follow-up and were excluded from the study. Second, we had problems with the supply of radionuclides, which affected the number of our patients. Finally, the follow-up period was relatively short. Further prospective studies may be planned to evaluate this technique in larger patient populations with longer follow-up.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eRadionuclide angiography has not yet been accepted as a routine method for determining the appropriate amputation level. Given its costs, its routine use is limited. However, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI technique may contribute to determining the amputation level and reducing the number of additional amputation attempts, considering the condition of the patients. With \u003csup\u003e99m\u003c/sup\u003eTc-MIBI, physicians\u0026rsquo; awareness about the amputation level in patients with DFU must be improved. Information gathered from \u003csup\u003e99m\u003c/sup\u003eTc-MIBI is likely to guide the method, course, and duration of treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe article has not been published anywhere before.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This study was not funded\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e: There is no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eLocal ethic committee approve was taken from the Kayseri City Education and Research Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate and Consent for publication:\u003c/strong\u003e The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eME designed the study. ME, HG and SK carried out the imaging and data collection part of the study in nuclear medicine and clinical areas. ME, AEG and FO performed the writing and statistical part.All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHoogeveen RC, Dorresteijn JAN, Kriegsman DMW, Valk GD. Complex interventions for preventing diabetic foot ulceration. Cochrane Database Syst Rev. 2015;2015:CD007610.\u003c/li\u003e\n \u003cli\u003eLee DW, Kwak SH, Kim JH, Choi HJ. Prediction of diabetic foot amputation using newly revised DIRECT coding system: Comparison of accuracy with that of five existing classification systems. Int Wound J. 2023;20:359\u0026ndash;71.\u003c/li\u003e\n \u003cli\u003eGazzaruso C, Gallotti P, Pujia A, Montalcini T, Giustina A, Coppola A. Predictors of healing, ulcer recurrence and persistence, amputation and mortality in type 2 diabetic patients with diabetic foot: a 10-year retrospective cohort study. Endocrine. 2021;71:59\u0026ndash;68.\u003c/li\u003e\n \u003cli\u003eJeon B-J, Choi HJ, Kang JS, Tak MS, Park ES. Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation. Int Wound J. 2017;14:537\u0026ndash;45.\u003c/li\u003e\n \u003cli\u003eBaykal YB, Yaman E, Burc H, Yorgancigil H, Atay T, Yildiz M. Is scintigraphy a guideline method in determining amputation levels in diabetic foot? J Am Podiatr Med Assoc. 2014;104:227\u0026ndash;32.\u003c/li\u003e\n \u003cli\u003eOzan F, G\u0026uuml;rb\u0026uuml;z K, \u0026Ccedil;elik I, Bestepe Dursun Z, Uzun E. Evaluation of major and minor lower extremity amputation in diabetic foot patients. Turk J Med Sci. 2017;47:1109\u0026ndash;16.\u003c/li\u003e\n \u003cli\u003eSarikaya A, Top H, Aygit AC, Benlier E, Unal Y. Predictive value of 99mTc-sestamibi scintigraphy for healing of extremity amputation. Eur J Nucl Med Mol Imaging. 2006;33:1500\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eCelen YZ, Zincirkeser S, Akdemir I, Yilmaz M. Investigation of perfusion reserve using 99Tc(m)-MIBI in the lower limbs of diabetic patients. Nucl Med Commun. 2000;21:817\u0026ndash;22.\u003c/li\u003e\n \u003cli\u003eLauri C, Leone A, Cavallini M, Signore A, Giurato L, Uccioli L. Diabetic Foot Infections: The Diagnostic Challenges. J Clin Med. 2020;9:1779.\u003c/li\u003e\n \u003cli\u003eAsli IN, Javadi H, Seddigh H, Mogharrabi M, Hooman A, Ansari M, et al. The diagnostic value of (99m)Tc-IgG scintigraphy in the diabetic foot and comparison with (99m)Tc-MDP scintigraphy. J Nucl Med Technol. 2011;39:226\u0026ndash;30.\u003c/li\u003e\n \u003cli\u003eMalone JM, Leal JM, Moore WS, Henry RE, Daly MJ, Patton DD, et al. The \u0026ldquo;gold standard\u0026rdquo; for amputation level selection\u0026quot; xenon-133 clearance. J Surg Res. 1981;30:449\u0026ndash;55.\u003c/li\u003e\n \u003cli\u003eRizk TH, Nagalli S. Technetium 99m Sestamibi. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Feb 3]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/books/NBK553148/\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003eTop H, Sarikaya A, Aygit AC, Benlier E, Kiyak M. Review of monitoring free muscle flap transfers in reconstructive surgery: role of 99mTc sestamibi scintigraphy. Nucl Med Commun. 2006;27:91\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eManevska N, Stojanoski S, Pop Gjorceva D, Todorovska L, Vavlukis M, Majstorov V. Tissue-muscle perfusion assessed by one day 99mTc-MIBI rest-dipyridamol scintigraphy in non-diabetic and diabetic patients. Rev Esp Med Nucl Imagen Mol (Engl Ed). 2018;37:141\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eNemcova A, Jirkovska A, Dubsky M, Bem R, Fejfarova V, Woskova V, et al. Perfusion scintigraphy in the assessment of autologous cell therapy in diabetic patients with critical limb ischemia. Physiol Res. 2018;67:583\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eLi Y, Li Q, Liang S, Liang X, Zhou W, He H, et al. A novel use of hill function and utility of 99mTc-MIBI scintigraphy to detect earlier lower extremity microvascular perfusion in patients with type 2 diabetes. Medicine (Baltimore). 2017;96:e8038.\u003c/li\u003e\n \u003cli\u003eZhang Q, Liu X, Li Q, Liu Y, He H, Wang K, et al. Quantitative model for assessment of lower-extremity perfusion in patients with diabetes. Med Phys. 2023;50:3019\u0026ndash;26.\u003c/li\u003e\n \u003cli\u003eCerqueira L de O, Duarte EG, Barros AL de S, Cerqueira JR, de Ara\u0026uacute;jo WJB. WIfI classification: the Society for Vascular Surgery lower extremity threatened limb classification system, a literature review. J Vasc Bras. 19:e20190070.\u003c/li\u003e\n \u003cli\u003eAygit AC, Sarikaya A. Imaging of frostbite injury by technetium-99m-sestamibi scintigraphy: a case report. Foot Ankle Int. 2002;23:56\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eAdiyeke L, Karagoz B. Analysis of Doppler ultrasonography and computer tomography angiography for predicting amputation level and re-amputation rate. North Clin Istanb. 2022;9:401\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eJbara M, Gokli A, Beshai S, Lesser ML, Hanna S, Lin C, et al. Does obtaining an initial magnetic resonance imaging decrease the reamputation rates in the diabetic foot? Diabet Foot Ankle. 2016;7:31240.\u003c/li\u003e\n \u003cli\u003eChou Y-Y, Hou C-C, Wu C-W, Huang D-W, Tsai S-L, Liu T-H, et al. Risk factors that predict major amputations and amputation time intervals for hospitalised diabetic patients with foot complications. Int Wound J. 2022;19:1329\u0026ndash;38.\u003c/li\u003e\n \u003cli\u003eBhatnagar A, Sarker BB, Sawroop K, Chopra MK, Sinha N, Kashyap R. Diagnosis, characterisation and evaluation of treatment response of frostbite using pertechnetate scintigraphy: a prospective study. Eur J Nucl Med Mol Imaging. 2002;29:170\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eSmith GT, Wilson TS, Hunter K, Besozzi MC, Hubner KF, Reath DB, et al. Assessment of skeletal muscle viability by PET. J Nucl Med. 1995;36:1408\u0026ndash;14.\u003c/li\u003e\n \u003cli\u003ePiwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. Circulation. 1990;82:1826\u0026ndash;38.\u003c/li\u003e\n \u003cli\u003eSarikaya I, Aygit AC, Candan L, Sarikaya A, T\u0026uuml;rkyilmaz M, Berkarda S. Assessment of tissue viability after frostbite injury by technetium-99m-sestamibi scintigraphy in an experimental rabbit model. Eur J Nucl Med. 2000;27:41\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eHesse B, Vinberg N, Mosbech H. Exanthema after a stress Tc-99m sestamibi study: continue with a rest sestamibi study? Clin Physiol Funct Imaging. 2011;31:246\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eMaucksch U, Runge R, Wunderlich G, Freudenberg R, Naumann A, Kotzerke J. Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI. Int J Radiat Biol. 2016;92:698\u0026ndash;706.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"amputation, diabetic foot ulcer, MIBI, 99mTc-MIBI, scintigraphy","lastPublishedDoi":"10.21203/rs.3.rs-4165516/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4165516/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThere is a positive relationship between mitochondrial damage in the cell and uptake in \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers. \u003csup\u003e99m\u003c/sup\u003eTc-MIBI scintigraphy should be considered in order to decide on the level of amputation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eProspectively twenty-four patients with diabetic foot ulcers (DFUs) were included in the study. As a result of treatment that started with the hospitalization, patients whose DFUs healed and did not need surgical intervention were determined as group 1, and patients whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention were determined as Group 2. 99mTc-MIBI scintigraphy was obtained before surgery. The \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of the injured foot relative to the healthy foot were recorded. Deep tissue culture was taken at surgery. ESR, WBC, CRP and albumin values of the patients were measured.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn this study, \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake rates of patients with poor prognosis were higher at all times than in patients who did not require revision surgery. A significant difference was found between these values in the 10th- and 30th-second rates. While the CRP level was 86.04\u0026thinsp;\u0026plusmn;\u0026thinsp;21.87 mg / dL in Group 1, it was measured as 144.43\u0026thinsp;\u0026plusmn;\u0026thinsp;27.54 mg / dL in Group 2 (p\u0026thinsp;=\u0026thinsp;0,040). There is a positive correlation between ulcerated foot / healthy foot 99mTc-MIBI involvement rates at 10 and 30 seconds and CRP values, and a negative correlation between albumin values.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThere is a significant relationship between \u003csup\u003e99m\u003c/sup\u003eTc-MIBI involvement rates and poor prognosis and reamputation. The correlation between CRP and albumin levels which are among the predictive values, and \u003csup\u003e99m\u003c/sup\u003eTc-MIBI uptake confirms this relationship. In diabetic foot ulcers, which are difficult to management and treatment.\u003c/p\u003e","manuscriptTitle":"Clinical value of Tc-99m MIBI scintigraphy for the level of lower limb amputation in patients with diabetic foot ulcers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-02 17:09:21","doi":"10.21203/rs.3.rs-4165516/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15cbee71-5a20-4d99-af75-b43dc4f8afa4","owner":[],"postedDate":"April 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-14T06:00:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-02 17:09:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4165516","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4165516","identity":"rs-4165516","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}