Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail

Accepted Manuscript Title: Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail Authors: Moses Lee, Woo Jin Choi, Seung Hwan Han, Jinyoung Jang, Jin Woo Lee PII: DOI: Reference:

S1268-7731(17)30138-8 http://dx.doi.org/doi:10.1016/j.fas.2017.07.006 FAS 1080

To appear in:

Foot and Ankle Surgery

Received date: Revised date: Accepted date:

16-2-2017 4-6-2017 6-7-2017

Please cite this article as: Lee Moses, Choi Woo Jin, Han Seung Hwan, Jang Jinyoung, Lee Jin Woo.Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail.Foot and Ankle Surgery http://dx.doi.org/10.1016/j.fas.2017.07.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Uncontrolled Diabetes as a Potential Risk Factor in Tibiotalocalcaneal Fusion using a Retrograde Intramedullary Nail

Moses Lee, M.D.b; Woo Jin Choi, M.D., Ph.D.a; Seung Hwan Han, M.D.a; Jinyoung Jang, M.D.a; Jin Woo Lee, M.D., Ph.D.a a

Department of Orthopaedic Surgery, Yonsei University College of Medicine b

Department of Orthopaedic Surgery, Inje University College of Medicine

※ Corresponding author: Jin Woo Lee Address: Department of Orthopaedic surgery, Yonsei University 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 120-752, Korea TEL: +82-2-2228-2195 FAX: +82-2-363-1139 E-mail: [email protected]

HIGHLIGHTS 1. This study looks at the results of 34 patients treated with tibiotalocalcaneal fusion using a retrograde intramedullary nail for a variety of indications.

2. With improved clinical outcomes, 82% (28/34) achieved successful union within seven months as evaluated by standard radiography.

3. Patients with uncontrolled DM are at increased risk of failure after TTC fusion with an odds ratio of 10.

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ABSTRACT Background: Tibiotalocalcaneal (TTC) fusion using a retrograde intramedullary (IM) nail is an effective salvage option for terminal-stage hindfoot problems. However, as many patients who receive TTC fusion bear unfavorable medical comorbidities, the risk of nonunion, infection and other complications increases. This study was performed to identify the factors influencing outcomes after TTC fusion using a retrograde IM nail. Methods: Between September 2008 and February 2012, 34 consecutive patients received TTC fusion using a retrograde IM nail for limb salvage. All patients had a minimum followup of two years. Throughout follow-up, standard ankle radiography was performed along with clinical outcome assessment using a visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society Ankle-Hind Foot Scale and the Foot and Ankle Outcome Score (FAOS). For the retrospective analysis, demographic factors, preoperative medical status, laboratory markers, and etiology were comprehensively reviewed using medical records. The success of the index operation was determined using clinical and radiological outcomes. Finally, the effect of each factor on failure after the operation was analyzed using univariate logistic regression. Results: In a mean of seven months, 82% (28/34) achieved union, as evaluated by standard radiography. All clinical outcome parameters improved significantly after the operation, including VAS, the American Orthopaedic Foot and Ankle Society Ankle-Hind Foot Scale

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(AOFAS A/H scale), and FAOS (P <0.001). At the last follow-up, five cases of nonunion with less than AOFAS A/H scale of 80 and two cases of below knee amputation due to uncontrolled infection were determined to be failures. None of the factors (etiology, demographics, laboratory markers and medical status) significantly influenced failures. However, uncontrolled DM significantly increased the failure rate with an odds ratio of 10 (P = 0.029). Conclusion: TTC fusion with a retrograde intramedullary nail is a successful treatment for complicated hindfoot problems such as traumatic osteoarthritis, Charcot arthropathy and failed TAA. However, it should be used judiciously in patients with uncontrolled DM, as the risk of failure increases.

Design: retrospective cohort study Keywords: Tibiotalocalcaneal arthrodesis; Intramedullary nailing; Diabetes Mellitus; Uncontrolled diabetes

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1. INTRODUCTION Tibiotalocalcaneal (TTC) fusion is considered to be an effective salvage procedure for endstage concomitant ankle and hindfoot pathologies. Such pathologies include traumatic hindfoot arthritis involving the subtalar joint, hindfoot arthritis accompanying nonunion or malunion of the tibia shaft, failed ankle arthrodesis, Charcot arthropathy, failed total ankle arthroplasty (TAA), and avascular necrosis of the talus.[1-4] To construct a stable and plantigrade foot, many techniques for TTC fusion using different implants (e.g. pins, screws, staples, plates, external fixators, and intramedullary nails) have been developed and reported in the literature.[2, 5-7] Among the various implants, biomechanical and anatomic studies have demonstrated the superiority of an intramedullary nail (IM nail) over other implants in terms of bending stiffness, rotational stability, and dynamic compression capability.[8-11] Indeed, several clinical studies have reported successful clinical outcomes, which achieved up to 100% union, after using a retrograde IM nail for TTC fusion for various indications.[3, 12-14] After all, orthopedic surgeons may encounter patients needing TTC fusion more frequently as life span increases in patients with TAA and/or diabetes. However, as most of the patients receiving TTC fusion have comorbid conditions, the risk of nonunion, infection, and major amputation is of great concern.[14-16] Since retrospective studies report union rates as low as 52% and global complication rates of 50%, TTC fusion with a retrograde IM nail is still a demanding procedure for orthopedic surgeons.[13, 17] Therefore, a study regarding prognostic factors after TTC fusion with a retrograde IM nail is important, as candidates for such surgery frequently bear unfavorable surgical factors. Nevertheless, few studies have analyzed prognostic factors after TTC fusion with a retrograde IM nail, while many studies have focused on biomechanical and clinical outcomes after the surgery.[6, 8, 10, 12-14, 18-22] To the authors’ best knowledge, there were only two studies 4

which specifically evaluated prognostic factors for TTC fusion with a retrograde IM nail. These studies presented opposite results, one with increased failure with an odds ratio of 7 in patients with DM, and the other study not identifying any significant factors affecting the fusion rate and functional results after TTC fusion using a retrograde IM nail. [12, 16] In this study, we tried to identify the factors that influence surgical outcomes after TTC fusion using a retrograde IM nail. The Institutional Review Board approved this retrospective cohort study.

2. MATERIALS AND METHODS 2.1 Patients Prior to the index operation, all patients signed an informed consent, which allowed using necessary medical records for future study. From September 2008 to February 2012, 38 patients were identified from a single institute as receiving TTC fusion for various hindfoot pathologies. Among them, four patients were excluded due to a limited follow-up period and/or use of a fixation implant other than a retrograde IM nail. For the remaining 34 cases, a comprehensive review of medical records and radiography was performed regarding demographic data, etiology of surgical indications, operative technique, associated medical conditions, union status via radiography, and postoperative complications. In addition, preoperative laboratory results were gathered to represent additional information on patients’ medical status (i.e. hemoglobin, white blood cell count, fasting serum glucose, serum creatinine, and albumin). Hemoglobin A1c (glycosylated hemoglobin) level had been ordered only for the patients with history of diabetes mellitus (DM). Since more than half of the patients (55.9%) had DM as a concurrent medical condition, a concept of uncontrolled 5

diabetes was adopted for detailed analysis. Based on previous publications, the following criteria for uncontrolled diabetes were used: Patients with a mean post-operative blood glucose level more than 200 mg/dL, hemoglobin A1c level more than 7.0%, or diabetes with short-term complications (ketoacidosis, hyperosmolarity, or diabetic coma).[23-25]

2.2 Clinical and radiographic evaluation Clinical and radiographic evaluations were performed on a regular basis. All patients were examined preoperatively and 6 weeks, 3 months, 6 months, 12 months, and thereafter annually after operation. For the clinical outcome assessment, the Visual Analog Scale (VAS), the American Orthopaedic Foot and Ankle Society Ankle-Hind Foot Scale (AOFAS A/H scale),[26] and the Foot and Ankle Outcome Score[27] (FAOS) were adopted to determine functions and the associated level of pain throughout the follow-up period. The AOFAS A/H scale was chosen, since it is the most widely used assessment tool for patients who had undergone foot and ankle surgery. In fact, the majority of studies evaluating outcomes after TTC fusion with a retrograde IM nail have used AOFAS A/H scale solely or in conjunction with other assessment tools.[12, 13, 18, 28-30] However, its lack of validation has been pointed out by some authors, and development of supplementary or new assessment tools was recommended.[31] Therefore, the FAOS was adopted to strengthen our clinical assessment. The FAOS uses patient’s self-reporting to evaluate functional status and limitations after foot and ankle operative procedures. Notably, the subscale regarding sports and recreational activities was omitted in this study, since the condition of most patients did not allow them to engage in sports or recreational activities which involved squatting, running, jumping or twisting of the affected foot and ankle.

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Radiographic evaluation was also performed in the same manner. For the preoperative assessment, standard anteroposterior and lateral weightbearing radiographs were performed. All patients presented with radiographic evidence of severe arthritis or destruction of both the ankle and subtalar joints. Postoperative radiographs were evaluated for bony union, which was defined as observation of bridging trabeculae in both the anteroposterior and lateral radiographs. If bony union was not achieved within 9 months after initial fixation and no progress was observed during the last 3 months of follow-up, the patient was diagnosed as having nonunion. For the purpose of this study, the following criteria were used to determine the success of the surgery: stable hind foot without pain or motion on physical examination, bony union at final radiography, and an AOFAS A/H scale or equal or greater than 80 according to the criterion of Saxena and Eakin[32]. Converted final AOFAS A/H scale was used for this criterion. In the case of stable pseudoarthrosis, which was defined as clinical union with radiolucency on either side of the ankle or subtalar joint, the result was considered as a success if the patient maintained the ability to ambulate without pain. Patients who did not meet the criteria were determined to be failures, including all major amputations. To minimize investigator bias, every clinical and radiological assessment was performed by an independent orthopaedic fellow who was blinded to the purpose of the study.

2.3 Operative procedure All cases were performed by the senior author (J.W.L.) using the same TTC fusion nail (DLA nail; U & I Corporation, Seoul, Korea). The nail had a compression feature at both ankle and subtalar joint with straight design. After general or spinal anesthesia, the patient 7

was placed on the operating table in the supine or semi-lateral position. A pneumatic tourniquet was applied on the proximal thigh. Different approaches were adopted, based on the previous operation scar and the pathology. For eight cases of failed total ankle arthroplasties (four cases referred from other hospitals), an anterior approach through the previous incision was used. After removing the failed prosthesis, fibrous soft scar tissue and necrotic material were removed. Thorough joint preparation was then performed using osteotomes, curettes, and rasps (Figure 1). Viability of the remnant bone stock was confirmed via bleeding from multiple holes drilled using Kirschner’s wire. Due to extensive bone loss, six out of eight cases required a bulk allograft (e.g. allo-talus or allo-femoral head). After denuding cartilage from the allograft, additional trimming was performed to fit the allograft into the prepared space. Bone grafting into the void was finalized with autologous iliac bone graft augmentation. For those without a prior surgery, a longitudinal skin incision was made at the lateral border of the distal fibula. After soft tissue dissection, an osteotomy site was chosen at the level of the syndesmosis. Harvested fibula was morselized to use for bone grafting. Both ankle and subtalar joint preparation was performed in the same manner. In addition, to reproduce neutral dorsiflexion of ankle joint with the hindfoot in 5 of valgus and external rotation, two Kirschner’s wires were placed temporarily. The plantar incision was placed at the crossing point between a longitudinal 3rd toe line and the junction of anterior and middle third of heel pad. After confirming alignment with fluoroscopy, a guide wire was inserted through a plantar incision from the calcaneus for retrograde IM nailing. At this point, the trajectory of a guide wire was carefully evaluated in both anteroposterior and lateral views to prevent iatrogenic shaft fracture during IM nail insertion. Intramedullary reaming was then performed sequentially. Reaming was continued until a chattering sound was heard, which was usually 0.5 to 1 mm larger than the desired nail size. A properly sized IM nail was introduced carefully along the guide wire. Finally, two transverse locking screws were placed 8

in the proximal tibia, while one mediolateral talar screw and one posteroanterior calcaneal screw were inserted distally.

2.4 Postoperative care The immobilization and non-weight-bearing periods were selected based on the etiology and condition of the patient. Generally, a short leg splint was applied for immobilization for two weeks after the operation. After the stitches were removed, a short leg cast was applied for an additional six weeks. The short leg cast was changed to a firm walker for an additional four weeks if bone union was observed to progress on the radiograph. Partial weight bearing was permitted beginning eight weeks after the operation. For patients who were diagnosed with Charcot arthropathy, the immobilization period was doubled, with close observation.

2.5 Statistical analysis All continuous variables were presented as means ± standard deviations. After confirming the Kolmogorov-Smirnov normality test, paired t-tests were performed to identify differences in preoperative and postoperative clinical outcomes (i.e., VAS, AOFAS A/H scale, and FAOS). Pearson chi-square tests or Fisher exact tests were used to compare failure rates regarding demographic and etiologic factors. Finally, univariate logistic regression was used to identify factors that were associated with failure after the index operation. A P value of < 0.05 was considered significant. Statistical analyses were performed by an independent biomedical statistician using SPSS statistical software (version 20.0, IBM Corp, Armonk, New York).

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3. RESULTS 3.1 Patients’ characteristics Baseline characteristics of the patients are listed in Table 1.

3.2 Clinical / radiological outcomes and complications All clinical parameters showed improvement after TTC fusion using a retrograde IM nail. Preoperative VAS scores averaged 7.5 (range, 2-10), which improved to an average of 3.0 (range, 0-6) at the last follow-up visit (P <0.001). The preoperative AOFAS A/H scale was 36 (range, 14-57) improving to 69 (range, 0-84) at the last follow-up visit (P <0.001). The original scores were converted based on 86 points maximum, resulted in an average score of 81 (range, 0-98). At the last follow-up, the mean FAOS for all sub-scores had improved significantly compared with the preoperative score (P <0.001, Table 2). Evaluation of serial radiography showed an 82.4% (28/34) union rate at the final follow-up. The average time until union was seven months. No significant differences in union rate or time were observed regarding etiology (P = 0.224, P = 0.373, respectively). Among the nonunion cases, one was determined to have a stable pseudoarthrosis. The patient had a stable ankle during physical examination and was able to ambulate with an ankle boot. However, at the final follow-up, a radiolucent line remained on the lateral view of the radiograph. During follow up after the operation, eight patients experienced major complications related to the TTC fusion with an IM nail. Major complications, such as nonunion and below knee amputation due to uncontrolled infection, were observed in six and two cases, respectively.

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3.3 Failure and prognostic factor analysis Seven patients showed unsuccessful results from the procedure, including two cases of below knee amputation and five cases of nonunion. All failing cases had fair to poor outcomes according to the clinical criteria. One case of nonunion having a stable pseudoarthosis was regarded as a successful outcome. This patient also had good clinical outcome criteria. To identify factors negatively affecting surgical outcomes, univariate logistic regression was performed. No demographic or etiologic factors showed significant results. Interestingly, elderly patients showed a trend toward less frequent failure, though the difference was not significant [OR = 0.23, (95% CI, 0.04-1.29, P = .097)]. Against patients without diabetes as a reference, patients with uncontrolled diabetes had a 10 times higher risk of developing failure [OR = 10.00, (95% CI, 1.26-79.33, P = .029)]. However, no significant difference was found comparing patients with controlled diabetes to those without diabetes. Other medical factors, including history of prior infection, use of bulk allograft, smoking and laboratory results, did not show significant results. The results of the univariate analysis are presented in Table 3.

4. DISCUSSION The present study analyzed the experience of a single surgeon using a retrograde IM nail for TTC fusion in various hindfoot pathologies. The technique was successful, with an overall union rate of 82% (28 of 34) with a mean time to union of 7 months. However, after further analyzing the data of patients with clinical failure, the result of this study suggest that poor glycemic control may negatively affect the operative outcome after TTC fusion with a retrograde IM nail.

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The concept of TTC fusion was first described by Lexer in 1906.[33] Since then, the nail design, configuration and technique have evolved.[19, 28] Since an IM nail allows a more reliable fixation due to inherent biomechanical stability, its use is indicated for most cases of TTC fusion for patients with end-stage hindfoot pathologies. These indications include salvage procedures for failed arthrodesis, failed TAA, and destroyed hindfoot after Charcot arthropathy.[1, 2, 13] The demographics of patients in the present study cohort showed a similar distribution of etiologies, with more than half of the patients (64.7%) having Charcot arthropathy or failed TAA. Furthermore, half of the patients (52.9%) receiving TTC fusion had a failed prior surgery. Along with biomechanical studies, most clinical studies of TTC fusion show successful outcomes. More specifically, radiographic studies show a 70-100% union rate, even in patients with poor bone stock and quality.[13, 14, 18, 34] The data from the present study are consistent with previous data, with a union rate of 82% observable within a mean of 7 months after the procedure. Patient outcome measurements also were satisfactory after the surgery. Although direct comparisons between studies are not feasible due to different operative techniques, diverse outcome measurement tools and heterogeneous study cohorts, many studies have used the AOFAS A/H scale as an adjunct or main outcome measurement tool. The mean AOFAS A/H scale after TTC fusion using an IM nail in a recent systematic review ranged from 35 to 82 points.[35] The AOFAS A/H scale scores ranged from poor to good clinical outcomes. The present study also demonstrated improved clinical outcomes with the AOFAS A/H scale scores increasing from 36 to 69 (converted final score: 80). However, as the AOFAS A/H scale lacks validation and demands careful interpretation, some of authors have adopted different outcome measurement tools, such as FAOS, AAOS-FAO, Mazur score and Japanese Orthopaedic Association score. In this study, the FAOS also was used, with

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subscores of 74, 42, 64, and 62 for pain, symptoms, ADL and QOL, respectively. This score range is comparable with the previous study, which showed 85 and 60 for the FAOS pain and QOL subscores.[36] Not all studies have reported favorable outcomes after TTC fusion with an IM nail. In the presence of adverse conditions such as medical comorbidities, poor bone stock or quality, poor soft tissue condition, and severe deformity, surgeons are more likely to encounter failures. In a meta-analysis reported by Jehan et al,[14] nonunion was the most common complication, present in as many as 48% of cases.[17] Also, the risk of infection was higher than those in general orthopedic procedures. Many studies reported over a 10% infection rate after retrograde IM nailing of the hindfoot.[12, 16, 17, 28, 34, 37] A deeply situated implant renders it difficult to control infections, and these infections can eventually lead to amputations unless treated properly. In this study, we also experienced two (5.8%) uncontrolled infections which required below-the-knee amputations. Other possible minor complications include plantar neurovascular damage at the entry site of the nail and stress fracture or complete fracture at the nail tip.[13, 38] Considering all the underlying risks, a study concerning prognostic factors after TTC fusion with an IM nail should be performed addition to general outcome analysis (i.e. union rate, outcome score and complication rate). However, most previous studies have focused mainly on clinical outcomes, complications regarding specific techniques and implants, comparisons of mechanical stability of different implants, and anatomic matters regarding the entry point of the nail. There are only a few reports regarding factors influencing outcomes after TTC fusion with a retrograde IM nail. In 2013, DeVries et al.[16] and Gross et al.[12] published contradictory results. The former study specifically reported a sevenfold increased odds ratio for amputation in patients with DM after TTC fusion with a

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retrograde IM nail. Additionally, revision surgery and preoperative ulceration increased the odds of failure by six and three times, respectively. However, the latter study did not find any factors that influenced the fusion rate and functional results. Several other studies also indicated that diabetes increases the risk of postoperative complications after foot and ankle surgery.[25, 39, 40] Nevertheless, this finding could not explain patients who present with favorable outcomes despite a history of DM. Thus, we postulated that there is a more specific factor leading to morbid outcomes among patients with DM. According to the study by Wukich et al.[41] patients with complicated DM had a 7.25-fold increased risk of surgical site infection after foot and ankle surgery compared with nondiabetic patients. However, the frequency of surgical site infection was not significantly different when uncomplicated DM patients was compare to nondiabetic patients. More recent study which stratified level of HbA1c (the inflection point > 7.5 mg/dL) also suggested significantly increased rate of surgical site infection following elective forefoot surgery.[42] The present study is consistent with these previous reports. Compared with patients without DM, patients with uncontrolled DM showed 10-fold increased odds of failure (Table 3). No other factors were found to be related to surgical failure. The following reasons could explain the current findings. In addition to altered foot biomechanics due to thickening of the Achilles tendon and plantar fascia, long term alteration of blood glucose levels directly debilitates postural control during standing, regardless of neuropathy.[43, 44] Also, bone healing is more impaired when glycemic control is poor. In a diabetic rat model, inhibition of chondrocyte production and mineralization in immature endochondral bone was observed in the poor glycemic control group.[45] Also, angiogenesis and cytokine production were diminished at the callus.[46] However, the optimal glycemic control group had normal mechanical properties without

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significant findings. Impaired immune response to infection has been observed in both clinical and laboratory experiments.[47] This combination of systemic and local malfunctions leads to failure after surgery. Furthermore, as patients with uncontrolled DM have a greater chance of having chronic complications, the possibility of having adverse conditions increases compared with patients with controlled DM.[40] There are several limitations in the present study. Due to a relatively small number of patients, a direct comparison between matched groups of successful and failed procedures was not performed. We tried to overcome this problem by using proper statistical methods considering various risk factors which might affect surgical outcomes. However, a future prospective study with a larger sample size is warranted to determine the effect of uncontrolled DM. Like the present study, most of the previous reports included 10 to 40 patients. To gather a large study cohort, a multicenter study would be a feasible solution. A retrospective study design has the potential for several biases, especially selection and observer bias. By excluding the senior author from data collection and analysis, this bias was minimized. Also, CT evaluation was not performed for the evaluation of union status. This might lead to overestimation of union rate in the current study. Lastly, though the study used established criteria for identifying uncontrolled DM, uncertainty remains due to the diverse clinical presentations of diabetes. Our results suggest that surgery should be delayed for patients with uncontrolled DM. However, since HbA1c takes times to show improvement, there is a lack of guidance as to when surgery should be re-scheduled. A prospective study with a large sample could aid in developing more accurate criteria for selecting patients to receive TTC fusion with a retrograde IM nail. In spite of these limitations, the present study also supports previous studies regarding a specific subset of patients. The study suggests that patients with uncontrolled DM are at

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increased risk of failure after TTC fusion with a retrograde IM nail, even though TTC fusion with a retrograde IM nail generally offers an opportunity for successful salvage for complex hindfoot problems.

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nail. Foot Ankle Int. 1997;18:699-704. [38] Thordarson DB, Chang D. Stress fractures and tibial cortical hypertrophy after tibiotalocalcaneal arthrodesis with an intramedullary nail. Foot Ankle Int. 1999;20:497-500. [39] Wukich DK, Lowery NJ, McMillen RL, Frykberg RG. Postoperative infection rates in foot and ankle surgery: a comparison of patients with and without diabetes mellitus. J Bone Joint Surg Am. 2010;92:287-95. [40] Wukich DK. Diabetes and its negative impact on outcomes in orthopaedic surgery. World J Orthop. 2015;6:331-9. [41] Wukich DK, Crim BE, Frykberg RG, Rosario BL. Neuropathy and poorly controlled diabetes increase the rate of surgical site infection after foot and ankle surgery. J Bone Joint Surg Am. 2014;96:832-9. [42] Cancienne JM, Cooper MT, Laroche KA, Verheul DW, Werner BC. Hemoglobin A1c as a Predictor of Postoperative Infection Following Elective Forefoot Surgery. Foot Ankle Int. 2017:1071100717705140. [43] Deschamps K, Matricali GA, Roosen P, Nobels F, Tits J, Desloovere K, et al. Comparison of foot segmental mobility and coupling during gait between patients with diabetes mellitus with and without neuropathy and adults without diabetes. Clin Biomech (Bristol, Avon). 2013;28:813-9. [44] Centomo H, Termoz N, Savoie S, Beliveau L, Prince F. Postural control following a selfinitiated reaching task in type 2 diabetic patients and age-matched controls. Gait Posture. 2007;25:509-14. [45] Beam HA, Parsons JR, Lin SS. The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus. J Orthop Res. 2002;20:1210-6. [46] Coords M, Breitbart E, Paglia D, Kappy N, Gandhi A, Cottrell J, et al. The effects of low-intensity pulsed ultrasound upon diabetic fracture healing. J Orthop Res. 2011;29:181-8. [47] Marchant MH, Jr., Viens NA, Cook C, Vail TP, Bolognesi MP. The impact of glycemic control and diabetes mellitus on perioperative outcomes after total joint arthroplasty. J Bone Joint Surg Am. 2009;91:1621-9.

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Figure 1

21

TABLE 1. Baseline Characteristics: demographics, medical status, laboratory results and etiologyα

N = 34 Demographic factors Mean age (years)

65.32 ± 10.13

Gender (male / female)

16: 18

2

BMI (kg/m )

24.08 ± 2.98

Follow-up (months)

48.55 ± 23.49

Medical status at preoperative evaluation ASA class

2.00 ± 0.92

DM (%)

19 (55.9)

Duration of DM* (years)

7.62 ± 10.04

ESRD

10 (29.4)

CAOD

5 (14.7)

Previous surgery on hindfoot

18 (52.9)

Prior infection history

10 (29.4)

Current Smoker

4 (11.8)

Habitual Drinker

2 (5.9)

Laboratory results at preoperative evaluation Hb (g/dL)

11.95 ± 1.84 3

3

WBC (x10 /mm )

7.24 ± 2.03

Albumin (g/dL)

4.07 ± 0.57

Glucose (mg/dL)

165.70 ± 92.95

HbA1c* (%)

7.46 ± 1.61

Creatinine (mg/dL)

2.10 ± 2.26

Etiology Charcot arthropathy

14 (41.2)

Failed TAA

8 (23.5)

Secondary OA

12 (36)

[Traumatic OA : RA : AVN : PS : SA]

[3:3:2:2:2]

α

Values are presented as mean ± standard deviation for the continuous variables. The categorical variables are presented as the number (%) of patients. Abbreviations: BMI, body mass index; ASA, American Society of Anesthesiologists; DM, Diabetes Mellitus; ESRD, End Stage Renal Disease; CAOD, Coronary Artery Occlusive Disease; TAA, Total Ankle Arthroplasty; OA, Osteoarthritis; RA, Rheumatoid Arthritis; AVN, Avascular Necrosis; PS, Polio sequelae ; SA, Septic arthritis *Parameters were measured only for the patients with history of DM

22

TABLE 2. Summary of outcomes: clinical outcome, radiological outcome, and complicationsα Clinical outcomes VAS, mean ± SD AOFAS score, mean ± SD FAOS score, mean ± SD Pain Symptom ADL QOL

Preoperative score

Postoperative score

P

7.55 ± 2.31

3.05 ± 1.22

<.001

36.05 ± 12.06

69.41 ± 21.21

<.001

32.50 ± 17.18 14.41 ± 4.72 26.94 ± 4.61

74.23 ± 3.91 42.61 ± 6.89 64.38 ± 5.95

<.001

5.88 ± 6.45

62.94 ± 4.65

<.001

Clinical outcome criteria, N (%)

<.001 <.001 <.001

Excellent/good (≥80)

0 (0%)

27 (79.4)

Fair/poor (<80)

34 (100%)

7 (20.6)

Radiological outcomes Union Time to union (month) Nonunion site (TT and TC joint / TT joint / TC joint)

28 (82.4%) 7.23 ± 3.26 5/1/0

Complications Major

Nonunion 6 cases Below knee amputation 2 cases

Minor

Superficial infection 1 case Peripheral neurologic symptom 2 cases α Values are presented as mean ± standard deviation for the continuous variables. The categorical variables are presented as the number (%) of patients. Abbreviations: VAS, visual analog scale; SD, standard deviation; AOFAS, American Orthopaedic Foot and Ankle Society; FAOS, Foot and Ankle Outcome Score; ADL, Activity of Daily Living; QOL, Quality of Life; TT, Tibiotalar joint; TC, Talocalcaneal joint Boldface type indicates statistical significance (P < 0.05).

23

TABLE 3. Univariate logistic regression analysis for predictors of failure after TTC fusionα Demographic & Etiologic factors Age ≥ 60 years Female BMI > 25 kg/m2 Charcot arthropathy Failed TAA Secondary OA

Failure No. of Failure / No. of patients (%)

OR (95% CI)

P

3/25 (12.0)

0.23 (0.04-1.29)

.097

3/18 (16.6) 3/13 (23.0) 3/14 (21.4) 3/8 (37.5) 1/12 (8.3)

0.85 (0.17-4.18) 1.88 (0.38-9.39) 0.81 (0.16-4.17) 2.52 (0.44-14.24) 0.53 (0.09-3.17)

.849 .437 .809 .296 .490

2/15 (13.3) 0/12 (0.0) 5/7 (71.4)

1.00 N/A* 10.00 (1.26-79.33)

N/A .999 .029

2/15 (13.3) 1/7 (14.2) 4/12 (33.3) 4/10 (40.0)

1.00 0.67 (0.05-7.85) 2.00 (0.35-11.43) 3.33 (0.63-17.51)

N/A .747 .436 .155

CAOD

3/5 (60.0)

7.20 (0.94-54.93)

.057

ASA ≥ 3 Prior infection history

2/10 (20.0)

1.62 (0.30-8.67)

.568

4/10 (40.0)

3.33 (0.63-17.51)

.155

Use of bulk allograft

3/12 (25.0)

2.25 (0.44-11.33)

.326

Current Smoker

1/4 (25.0)

1.09 (0.09-12.26)

.941

Habitual Drinker

0/2 (0.0)

N/A

.999

Serum Glucose ≥ 140mg/dL

5/13 (38.4)

3.75 (0.71-19.64)

.118

Serum Glucose ≥ 200mg/dL

3/10 (30.0)

1.62 (0.30-8.67)

.568

0/2 (0.0)

N/A*

.999

Medical status Diabetic status without diabetes Controlled diabetes Uncontrolled diabetes Duration of DM None diabetic patients < 10 years  10 years ESRD

Laboratory results

Albumin < 3.5 g/dL

4/9 (44.4) 4.290 (0.77-22.86) .097 Creatinine ≥ 1.5 mg/dL Abbreviations: OR, Odds ratio; CI, Confidence interval; N/A, Not applicable; BMI, body mass index; TAA, Total Ankle Arthroplasty; OA, Osteoarthritis; DM, Diabetes Mellitus; ESRD, End Stage Renal Disease; CAOD, Coronary Artery Occlusive Disease; ASA, American Society of Anesthesiologists; *Unable to determine CI because no failure occurred in the index category

α

Boldface type indicates statistical significance (P < 0.05)

24