Materials and methods

This is a prospective, observational and longitudinal study. Consecutive non-randomized non-probabilistic sampling was carried out in a 3-month time period in 15 diabetic foot care centers in Argentina of different levels of complexity. They were chosen given that the members of the Diabetic Foot Committee of the Argentine Diabetes Society work in the diabetic foot teams of that institu tions, which facilitated data collection. The characteris tics of the participating centers are shown in Table 1 and the levels of each center referring to the complexity of diabetic foot care are shown in Table 2 ^7,8.. Responsibility in data collection and in the veracity of the information cor responds to the researchers of each center. Patients with diabetes over 18 years of age who consulted for a new foot lesion between 04/01/22 and 06/30/22 were included. Pregnant patients or those who did not sign informed consent were excluded. Different characterization vari ables were recorded, such as age, sex, years of diabetes evolution, type of diabetes (1, 2 or others), history of car diovascular disease (stroke, acute myocardial infarction), arterial hypertension, history of major amputation, his tory of minor amputation, chronic renal failure on dialy sis, cause of injury (trauma, shoe rubbing, nail clipping, neuropathic ulcer, burn, mycosis), smoking, history of heart failure. The infection was assessed according to the IDSA9 classification in mild infection: cellulitis < 2cm without osteomyelitis or systemic symptoms; moderate infection: cellulitis >2cm, gangrene, abscess, gas, deep tissue involvement, osteomyelitis and severe infection: presence of systemic inflammatory symptoms and signs (fever, leukocytosis, leukopenia, tachycardia, tachypnea. Ischemia was assessed using the ankle-brachial index (ABI). It was performed with portable Doppler equipment with an 8 MHz probe and consists of the highest pressure of the limb (posterior tibial or pedal artery) on the highest of the two arms. Patients with mild ischemia were de fined as those with an ABI 0.7 to 0.89 or slightly decreased pulses, moderate ischemia as those with an ABI 0.50 to 0.69 or barely palpable pulses, and severe ischemia as those with an ABI <0.5 or absent pulses. No ischemia was defined as a value of 0.9 to 1.4 or palpable pulses. A higher value was interpreted as arterial calcification and in this situation the pulses were taken into account as in those in whom the ABI could not be performed for some rea son. The patients were classified according to their risk using the application of the Argentine Diabetes Society “Classifications in diabetic foot/ Risk score” for Android. The Saint Elian (SEWSS), IDSA, Texas, SINBAD, WIfI clas sifications were used.^9-13 WIfI consists of classifying pa tients with diabetic foot and assigning a higher amputa tion risk and revascularization benefit according to the characteristics of the wound. This risk ranges from 1 (very low) to 4 (high). Saint Elian is a score in which the sum of points can give a score from 6 to 30, with higher values being more serious and with a worse prognosis. SINBAD is a score, with dichotomous variables that add up to one point when present and can add up to a maximum of 6 points. Assess the site of the lesion, presence of ischemia, neuropathy, infection, area, and depth. IDSA is a classi fication that divides infections into 4 categories (no in fection, mild, moderate, and severe) previously described. Texas is a table with 16 boxes, where 4 degrees and 4 stages are combined, relating the depth of the lesion with the presence of ischemia, infection or both. Neuropathy was assessed by clinical methods (monofilament, tuning fork). Charcot Neuroarthropathy was assessed based on clinical presentation and radiographs. A 6-month follow-up was carried out, where the date of admission to the operating room, revascularization, percentage of minor amputation, primary result (if it was amputated, died or healed before 6 months) and the result in the 6-month follow-up were recorded (major amputation, death, lost to follow-up, healing or persistence of the lesion). Ma jor amputation above the infrapatellar or supracondylar level, minor amputation below that level (transmetatar sal, toe amputation) and healing of fully epithelialized le sions were defined.

Table 1 Participating centers and researchers’ data 

Table 2 Characteristics of levels referring to the complexity of diabetic foot care 

Results

A total of 312 patients belonging to 15 cen ters in Argentina were analyzed, of which 76.6% (n = 239) were male, with a mean age of 58.1 (12.1). Ninety five percent (n = 295) had type 2 diabetes. 43% (n = 133) required hospitalization at the time of the first visit. Their background and characteristics are summarized in Table 3.

Table 3 Antecedents and comorbidities of the patients 

Peripheral arterial disease and infection

In relation to vascular compromise, ischemia was assessed with ABI in 253 patients and by palpation of pulses in the rest. The median ABI was 0.90 (0.64-1.10), excluding from the analy sis patients with arterial calcification, that is, ABI>1.4 (n = 32).

Patients without ischemia constituted 52.9% of the total (n = 165), those with mild ischemia 18.3% (n = 57), moderate 16.3% (n = 51) and se vere 12.5% (n = 39). Angiography was performed in 50 patients (16%). Median days to angiography was 12 (3-34). In 32 (64% of those in whom an giography was performed) some type of revas cularization was performed (endovascular 68.8% (n = 22), surgical 25% (n = 8) or both 6.3% (n = 2)). The median number of days to revascularization was 14 (6-39). The reasons for which the rest of the patients were not revascularized were re nal failure, non-revascularizable ischemia, poor condition of the patient, extensive loss of tissue, delay in the provision of supplies (stent, bal loon). With regard to infectious involvement, 234 patients (75%) had some degree of infection at the time of consultation. The distribution of pa tients according to its severity (IDSA) is shown in Figure 1.

Figure 1 Distribution of patients according to the severity of the infections Mild infection: cellulitis < 2cm. No osteomyelitis or systemic symptoms Moderate infection: cellulitis > 2 cm, gangrene, abscess, gas, deep tissue involvement, osteomyelitis. Serious infection: presence of systemic inflammatory symptoms and signs (fever, leukocytosis, leukopenia, tachycardia, tachypneaThe values correspond to binary logistic regression with bivariate analysis. Categorized variables 

Follow-up results

During the study, the percentage of total ma jor amputation was 8.33% (CI95; 5.5-11.9) (n = 26) and that of minor amputation was 29.17% (CI95%; 24.2-34.6) (n = 91). At the 6-month follow-up, the percentage of death was 4.49% (95%CI; 2.5-7.4) (n = 14), 58.0% (95%CI; 52.9-64.2) (n = 181) healed, 24.3% (95%CI;19.6-29.5) had the wound still open (n = 76) and 7.37% were lost to follow-up (n = 23). During follow-up, 25 patients (8%) (95%CI; 5.2- 11.6) developed a new lesion. Of the patients who underwent a major amputation before 6 months (n = 24), 5 died (20.8%) in contrast to 3% of those who did not have an amputation (p = 0.001). The results of the 6-month follow-up for each center are described in Table 4. Patient factors and se verity of lesion in relation to major amputation and mortality in Table 5. In Table 6, a logistic re gression was performed with analysis of each variable of the Saint Elian scale separately in a categorized manner in relation to death, healing and major amputation. The condition of more than two aspects, moderate or severe ischemia, unilateral or bilateral edema, moderate or severe infection, depth of the lesion, area greater than 10 cm² and the healing phase (granulation or in flammation), were factors that were related in in versely with healing. The characteristics associ ated with major amputation were tarsal location, topographic appearance, multiple locations, se vere ischemia, bilateral edema, and severe infec tion. Finally, those related to death were severe ischemia and location in multiple areas. Table 7 shows the evolution of the patients at 6 months in relation to the degree of ischemia and revas cularization procedure.

Table 4 Results at 6-month follow-up 

Table 5 Patient factors and lesion severity associated with major amputation and death 

Table 6 Characteristics of the lesions included in the Saint Elian score related to major amputation, healing and mortality OR 95% CI 

Table 7 Evolution of the patients at 6 months in relation to the degree of ischemia and revascularization procedure 

Discussion

The evolution of patients with DF in Argenti na in a multicenter longitudinal analysis has not been previously published to our knowledge. In recent years, some studies have been carried out in our region in order to provide local data on the prevalence of DF in hospitalization, local mi crobiology in diabetic foot infections, and the use of classifications^3,10,14-16 although the ampu tation and mortality rates in these patients had not been studied up to now. In this study, it was possible to collect information that was previ ously unknown in the country, regarding the percentage of major amputation, death, minor amputation, and healing in patients who con sulted for diabetic foot in a 6-month follow-up. Although the major amputation rate at 6 months was 8.33%, this number varies according to each center, as shown in Table 4, with values ranging from 3.3% to 27.3%. This high variability could be explained by the heterogeneity in the care teams, the resources available for treatment, the seriousness with which patients arrive, and the lack of networks for timely referral. Many pa tients consult after several weeks and even months from the development of the lesion, having been incorrectly treated, causing delays in the establishment of adequate treatment. In fact, in our work, the median number of days since the lesion developed was 20, 61% had pre viously consulted another doctor and 43% of the patients required hospitalization at the first consultation given the severity of the lesion. It is also important to mention the diversity of crite ria for the surgical approach that is often at the mercy of the availability of operating rooms and the will of the surgeon on duty who is generally not a specialist in DF. In general, DF teams lack a surgeon or traumatologist with knowledge and commitment on the subject and, even if they do, many decisions in the emergency depend on who is attending in the emergency department. Despite having national and international guidelines that mention the treatment algo rithms for these patients, the heterogeneity of the lesions, the scarce symptomatology and the lack of interest of doctors in this pathology often leads to make decisions without experience or knowledge of it. Some studies mention that the personal beliefs of physicians result in subopti mal treatments when there are no clear guide lines for care (surgical, infectious, and revascu larization treatments)^17,18. Table 8 describes the results of other similar studies in other coun tries, showing great variability in the results of the different regions in terms of major and mi nor amputation, healing, and death. This fact may be related to a number of reasons (besides the ones listed above) and this is why knowl edge of local data is important. An example of this is the percentage of patients with ischemia in the different studies that can condition the results, since it has been a factor constantly as sociated with poor evolution (amputation and death). Ford et al. published in 2020 a retrospec tive study on the follow-up of 98 patients with DF¹⁹. A 5-year follow-up was performed, report ing an amputation rate of 28.6% and a death rate of 13.3%. This amputation rate is higher than in other studies and could be related to the high percentage of patients with ischemia (72% of the patients had diabetes, all ischemic), which may influence the results. Also, a sample with a high percentage of patients with serious infections such as diabetic foot attack can increase mortal ity, as in the study by Vas et al²⁰. In this study, 106 patients with diabetic foot attack were followed up for 18 months. This research group reported a mortality of 40% at the end of follow-up, higher than in other studies. Other factors that may be related to amputation and mortality rates are the resources available for prevention, diagno sis, and treatment of patients. In a review car ried out on studies in African countries²¹ on 56173 patients with diabetes, an amputation rate greater than 15.5% and death rate of 14.2% (95% C.I. 9.9-19.0) were reported in contrast to the Eurodiale study¹⁸, where different countries in Europe and the major amputation rate was 5% and mortality 6%. Certain characteristics of the patients and injuries are related to major amputation in most studies (Table 8), such as age, presence of ischemia, CRF on dialysis, gangrene, neuropathy, and certain scales and clas sifications. In our study, age, WIfI classification, the Saint Elian and SINBAD scales, and the ABI were associated with major amputation and death. A history of cardiovascular disease was also related to the latter. Among the characteris tics of the lesions, we found that tarsal location, multiple involvement, severe ischemia, bilateral edema, and severe infection were related to ma jor amputation. The presence of neuropathy was not related to major amputation, unlike the original study of the Saint Elian scale (SEWSS)¹². It should be noted that parameters of glycemic control, autonomic neuropathy, microalbumin uria, or CRP (C-reactive protein) were not ana lyzed in our study. Regarding PAD, our study did not show a statistically significant improvement in the results of patients with ischemia who un derwent revascularization, as shown in Table 7, probably because the sample was insufficient to perform this analysis. We consider it necessary to conduct research on patients with ischemia by increasing the sample size in order to assess the implication of revascularization on the re sults. The lack of early diagnosis of NC and its consequences make this a very fearsome dis ease with serious consequences. Forty-eight percent of the patients in our work consulted previously and their disease was never recognized nor was an appropriate discharge indicat ed. The consequences of the lack of discharge can be irreducible foot deformations that lead to recurrent ulcers (in these cases the therapeutic solution is amputation or very complex surgeries). Twenty-four patients in our series with Charcot presented with an ulcer, perhaps as a consequence of the aforementioned. The educa tion of primary care physicians in the recogni tion of this disease in its early stages is essential to avoid its serious consequences. Finally, we believe it is necessary to mention that the mor tality of patients who underwent a major ampu tation is around 35% to 50% at five years^6,22, com pared to 9% mortality from breast cancer, 30% mortality from any cancer and only less than that caused by lung cancer (80%)²². In our study, of the patients who underwent a major amputa tion before the 6 months follow up (n = 24), 20.8% died within that period. But also, although the death of these patients is generally of a car diovascular cause^6,20 DF and major amputation are not only disease markers but are also independent factors of premature death²³. For this reason, we consider as a priority the need to avoid major amputations, which also constitute an increase in health costs, loss of income, fi nancial aid allocations, deterioration of the quality of life of the patient and family mem bers. For this, it is necessary to know the charac teristics of the patients who consult in our envi ronment in order to prioritize the care of those most prevalent factors and assign and optimize the means for their prevention and treatment based on this information. It is necessary to de termine what would be the best distribution of resources, optimizing hemodynamic studies for care of ischemia (more than half of the patients had some degree of ischemia), improving the provision of antibiotics for the treatment of infection (75% had infection), assigning the pay ment of trauma modules to suitable and interested professionals to reduce hospitalization rates and times (43% required hospitalization and 29% required a minor amputation), or allo cating more resources to primary care to im prove prevention and training of primary care physicians and residents in a combined approach on prevention, routine screening, and ag gressive intervention protocols for cardiovascular risk factors (more than 60% of patients had consulted another professional previously)²³. Actions are needed at the governmental level that indicate clear guidelines in the treatment of patients and arbitrate the means to support interdisciplinary teams that work to reduce hospi talizations, major amputations and death. Knowledge of local data about the amputation rate, mortality, hospitalization rate, and patient characteristics will improve decision-making in terms of health policies based on solid data, access to diagnostic resources by different institutions. and treatment, optimization of referral and counter-referral, and training of the differ ent levels in the timely diagnosis and treatment of these patients in order to avoid major amputations.

Table 8 Published studies with longitudinal follow-up of patients with diabetic foot and factors related to major amputation