Kliničke i histomorfološke promene hronične ulceracije dijabetičnog stopala nakon otklanjanja mehaničkog stresa na stopalo

UVOD: Hronične rane se definišu kao rane koje nisu blagovremeno i adekvatnim redosledom dovršile reparativne procese u cilju uspostavljanja anatomskog i funkcionalnog integriteta u toku 6 nedelja. Procenjuje se da 1-2% populacije u razvijenim zemljama boluje od hronične rane. Najveći procenat hroničnih rana se javlja kod dijabetičara. Sve hronične rane karakteriše prolongirana i pojačana proinflamatorna kaskada što ne dozvoljava započinjanje proliferativne faze zarastanja rane. Poremećena glikoregulacija kod dijabetičara dovodi do razvoja endoteliopatije i neuropatije. Kao posledica ovih promena se javlja stopalna ulceracija. Osnovni postulati lečenja stopalne ulceracije podrazumevaju zaustavljanje ponavljanog oštećenja tkiva uzrokovanog posturalnim mehaničkim pritiskom, debridman rane, kontrolu infekcije i inflamacije, adekvatno previjanje i adekvatnu regulaciju glikemije. Sve mere imaju za cilj smanjenje stimulacije imunskih ćelija i produkcije proinflamatornih citokina, proteaza i reaktivnih kiseoničnih radikala. Željeni rezultat su morfološke i biohemijske promene koje će omogućiti hroničnoj rani da progredira iz inflamatorne u proliferativnu fazu i time dovrši proces zarastanja. CILJ: Utvrditi kliničke i histomorfološke promene u hroničnoj ulceraciji dijabetesnog stopala kod pacijenata kod kojih je primenjena terapija rasterećenja od mehaničkog pritiska, modifikovanom totalnom kontaktnom imobilizacijom, kao i ispitati korelaciju između brzine i obima zarastanja hronične ulceracije dijabetesnog stopala i promene histomorfoloških parametara u odnosu na primenu modifikovane totalne kontaktne imobilizacije. MATERIJAL I METODE: Prospektivnim istraživanjem je uključeno 80 ispitanika, starijih od 18 godina, koji boluju od dijabetesa sa dobrom glikoregulacijom (HbA1C ≤ 8%), a koji imaju neuropatsku ulceraciju na plantarnoj strani stopala, bez znakova infekcije i išemije (ankle-bračial index, ABI ≥ 0,7) u prethodnih 8 nedelja (SINBAD skor ≤ 3). Ispitanici su nasumično podeljeni u dve grupe, od po 40 ispitanika. Prvoj grupi (TKI grupa) je nakon inicijalnog pregleda postavljena totalna kontaktna imobilizacija, koju su nosili tokom tri nedelje, nakon čega je ulkusna promena bioptirana. Ovoj grupi ispitanika je, nakon skidanja totalne kontraktne imobilizacije, rana previjana tokom naredne 4 nedelje. Drugoj, kontrolnoj grupi (K grupa), ispitanika je biopsija ulkusne promene uzeta nakon incijalnog pregleda. Ovi ispitanici su praćeni i previjani, na isti način kao i prva grupa, tokom 4 nedelje. Pored patohistološke analize uzete biopsije ulkusne promene, vršeno je merenje površine rane, pre, tokom i nakon završenog tretmana. REZULTATI: U istraživanju je učestvovalo 59 (73,7%) muškaraca i 21 (26,3%) žena, prosečne starosti 65,4 godine. Većina ispitanika nije imala štetne navike (pušenje, konzumiranje alkohola). Većina ispitanika je imala tip 2 dijabetes melitus (72; 92,5%), bez statistički značajne razlike između TKI i K grupe (Fisher’s exact test = 0,72; p = 0,68). Prosečna vrednost ABI za TKI grupu je iznosila 0,90 ± 0,19, dok je za K grupu iznosila 0,91 ± 0,14, bez statistički značajne razlike između grupa ((U=755,50; p = 0,66). Klasifikacija ulkusnih promena vršena je prema SINBAD klasifikacionom sistemu. Kod svih ispitanika je gradus 1 imalo 33 (41,2%), gradus 2 15 (18,8%) a gradus 3 je imalo 32 (40%) ispitanika. Nije utvrđena statistički značajna razlika između ispitanika sa totalnom kontaktnom imobilizacijom i ispitanika iz kontrolne grupe sa različitim SINBAD gradusima (χ2 test = 1,95; p = 0,38). Prosečno trajanje ulceracije pre početka tretmana je u TKI grupi iznosilo 5 meseci (najkraće 1 mesec, najduže 24 meseca), dok je u K grupi bilo 3 meseca (najkraće 1 mesec, najduže 19 meseci), bez statistički značajne razlike između grupa (U=637,00; p = 0,11). Prosečna površina ulceracije pre početka tretmana je kod TKI grupe iznosila 2,46 ± 1,22 cm2, a kod K grupe 2,52 ± 1,14 cm2 , bez statistički značajne razlike među grupama (U = 752,50; p = 0,65). Otkrivena je jaka pozitivna korelacija između dužine trajanja i površine ulceracije pre početka tretmana (r = 0,74; p < 0,001). Kod najvećeg broja ispitanika TKI grupe (23; 57,5%) je ulceracija trajala kraće od 5 meseci sa prosečnom površinom 0,56±0,14 cm2, dok je kod 17 (42,5%) ispitanika iste grupe trajala duže od 5 meseci sa prosečnom površinom 1,87±0,33 cm2. Utvrđena je statistički značajno manja površina ulceracije kod pacijenata koji su imali trajanje ulkusa kraće od 5 meseci (U = 73,00; p = 0,001). Kod TKI grupe je došlo do smanjenja površine ulceracije već nakon 3 nedelje nošenja imobilizacije za prosečno 28,23%, prosečna vrednost površine iznosila je 1,81 ± 1,13 cm2, a na kraju tretmana se površina ulceracije smanjila za 61,87% u odnosu na inicijalnu površinu, prosečne vrednosti površine 1,12 ± 1,20 cm2. U kontrolnoj grupi je na kraju tretmana došlo do povećanja prosečne površine rane za 13,05 ± 19,86% u odnosu na prosečnu inicijalnu površinu hronične ulceracije. Kod TKI grupe je, kod 38 (95%) ispitanika, patohistološkom analizom verifikovana distribucija granulacionog tkiva i neovaskularizacije na više od 66% površine pregledanog uzorka biopsije. Kod kontrolne grupe je kod najvećeg broja ispitanika, patohistološkom analizom dobijen rezultat najveće distribucije inflamatornih ćelija, ćelijskog debrisa, hiperkeratoze i fibroze. Utvrđena je statistički značajna povezanost između vrste tretmana i konačnog išoda nakon tretmana (Fisher’s exact test = 61,59; p < 0,001). Korelacioni koeficijent (Cramer’s V = 0,88; p < 0,001) ukazuje na jaku pozitivnu korelaciju između ove dve varijable. Od ukupnog broja ispitanika sa poboljšanim stanjem hronične ulceracije, čak 36 (97,3%) ispitanika pripada grupi koja je nosila totalnu kontaktnu imobilizaciju, dok je samo 1 (2,7%) ispitanik iz kontrolne grupe imao poboljšano stanje hronične ulceracije. Bez poboljšanog stanja hronične ulceracije, bilo je samo 4 (9,3%) ispitanika koji su nosili totalnu kontaktnu imobilizaciju, dok je 39 (90,7%) ispitanika bilo iz kontrolne grupe. ZAKLJUČAK: Lečenje hronične ulceracije dijabetesnog stopala primenom totalne kontaktne imobilizacije, dovodi do mehaničkog rasterećenja od posturalnog pritiska na gaznu površinu, čime se pokreću reparativni procesi u hroničnoj ulceraciji sa konsekutivnim bržim smanjenjem površine i dubine rane. Histomorfološke promene ove terapije se odlikuju redukcijom inflamatornih ćelija, ćelijskog i bakterijskog debrisa, fibroze i hiperkeratoze u ulkusu kao i povećanjem neoangiogeneze i stvaranjem granulacionog tkiva. Raniji početak terapije mehaničkog rasterećenja i kraće trajanje ulkusa povoljno utiču na brzinu zarastanja rane. Mehanički debridman i redovno previjanje antiseptičnim rastvorom dovode do većeg obima i bržeg zarastanja hronične ulceracije kod pacijenata kod kojih je pre tretmana primenjena totalna kontaktna imobilizacija, u odnosu na grupu pacijenata kod kojih nije primenjeno rasterećenje od mehaničkog pritiska na ulkus.
INTRODUCTION: Chronic wounds are defined as wounds that have not completed the reparative processes in a timely and adequate order in order to establish anatomical and functional integrity within 6 weeks. It is estimated that 1-2% of the population in developed countries suffers from a chronic wound. The highest percentage of chronic wounds occurs in diabetics. All chronic wounds are characterized by a prolonged and intensified pro-inflammatory cascade that does not allow the initiation of the proliferative phase of wound healing. Disturbed glycoregulation in diabetics leads to the development of endotheliopathy and neuropathy. As a consequence of these changes, foot ulceration occurs. The basic postulates of treating foot ulceration include stopping repeated tissue damage caused by postural mechanical pressure, debridement of the wound, control of infection and inflammation, adequate dressing and adequate regulation of glycemia. All measures are aimed at reducing the stimulation of immune cells and the production of pro-inflammatory cytokines, proteases and reactive oxygen radicals. The desired result is morphological and biochemical changes that will allow the chronic wound to progress from the inflammatory to the proliferative phase and thereby complete the healing process. OBJECTIVE: To determine the clinical and histomorphological changes in chronic diabetic foot ulceration after mechanical pressure relief therapy (off-loading therapy), with modified total contact cast, as well as to examine the correlation between the speed and extent of healing of chronic diabetic foot ulceration and changes in histomorphological parameters in relation to the use of modified total contact cast. MATERIALS AND METHODS: A prospective study included 80 patients, over 18 years of age, who suffer from diabetes with good glycoregulation (HbA1C ≤ 8%), and who have plantar neuropathic ulcer, without signs of infection and ischemia (ankle-brachial index , ABI ≥ 0.7) in the previous 8 weeks (SINBAD score ≤ 3). Patients were randomly divided into two groups (40 patients each). After the initial examination, the first group (TCC group) underwent off-loading treatment using total contact cast, which they wore for three weeks, after which the ulcer was biopsied. For this group of patients, after removing the total contact cast, the wound was bandaged twice a week, during the next 4 weeks. The second, control group (C group), had a biopsy of the ulcer taken after the initial examination. These subjects were bandaged twice a week, in the same way as the first group, for 4 weeks. In addition to the pathohistological analysis of the biopsy of the ulcer, the wound surface was measured before, during and after the treatment. RESULTS: 59 (73.7%) men and 21 (26.3%) women participated in the research, with an average age of 65.4 years. Most of the patients had no harmful habits (smoking, alcohol consumption). Most patients had type 2 diabetes mellitus (72; 92.5%), with no statistically significant difference between the TCC and C groups (Fisher's exact test = 0.72; p = 0.68). The average ABI value for the TCC group was 0.90 ± 0.19, while for the C group it was 0.91 ± 0.14, with no statistically significant difference between the groups (U=755.50; p = 0.66) The classification of ulcer changes was performed according to the SINBAD classification system 33 (41.2%) of all subjects had grade 1, 15 (18.8%) grade 2 and 32 (40%) grade 3 subjects. It was not determined statistically significant difference between patients with total contact cast and patients from the control group with different SINBAD grades (χ2 test = 1.95; p = 0.38). The average duration of ulceration before the start of treatment was 5 months in the TCC group (the shortest was 1 month, the longest was 24 months), while in the C group it was 3 months (the shortest was 1 month, the longest was 19 months), with no statistically significant difference between the groups (U=637.00; p = 0.11). The average area of ulceration before the start of treatment in the TCC group was 2.46 ± 1.22 cm2, and in the C group 2.52 ± 1.14 cm2, with no statistically significant difference between the groups (U = 752.50; p = 0.6 5). A strong positive correlation was found between the duration and the area of ulceration before the start of treatment (r = 0.74; p < 0.001). Majority of the patients in the TCC group (23; 57.5%), had the ulceration less than 5 months with an average surface area of 0.56±0.14 cm2, while in 17 (42.5%) patients, in the same group, it lasted longer than 5 months with an average surface area of 1.87±0.33 cm2. A statistically significantly smaller surface area of ulceration was found in patients who had an ulcer lasting less than 5 months (U = 73.00; p = 0.001). In the TCC group, there was a decrease in the ulcer surface area, already after 3 weeks of wearing cast by an average of 28.23%, the average value of the surface area was 1.81 ± 1.13 cm2, and at the end of the treatment, the surface area of ulceration decreased by 61.87% in relation to the initial surface area, average values 1.12 ± 1.20 cm2. In the control group, at the end of the treatment, there was an increase in the average surface area of the wound by 13.05 ± 19.86% compared to the average initial surface area of chronic ulceration. In the TCC group, in 38 (95%) patients, pathohistological analysis verified the distribution of granulation tissue and neovascularization on more than 66% of the surface area of the examined biopsy sample. In the control group, the pathohistological analysis showed the highest distribution of inflammatory cells, cellular debris, hyperkeratosis and fibrosis in the majority of patients. A statistically significant association was found between the type of treatment and the final outcome after treatment (Fisher's exact test = 61.59; p < 0.001). The correlation coefficient (Cramer's V = 0.88; p < 0.001) indicates a strong positive correlation between these two variables. Of the total number of subjects with an improved chronic ulceration condition, as many as 36 (97.3%) patients belong to the group that wore total contact cast, while only 1 (2.7%) subject from the control group had an improved chronic ulceration condition. Without improved chronic ulceration, there were only 4 (9.3%) patients who wore total contact cast, while 39 (90.7%) subjects were from the control group. CONCLUSION: Treatment of chronic ulceration of the diabetic foot using total contact cast leads to mechanical relief from postural pressure on the tread surface, which triggers reparative processes in chronic ulceration with a consecutive faster reduction of the surface area and depth of the wound. The histomorphological changes of this therapy are characterized by a reduction of inflammatory cells, cellular and bacterial debris, fibrosis and hyperkeratosis in the ulcer, as well as an increase in neoangiogenesis and the formation of granulation tissue. An earlier start of off-loading therapy and a shorter duration of the ulcer have a favorable effect on the speed of wound healing. Mechanical debridement and regular dressing with an antiseptic solution lead to a more extensive and faster tissue repair of chronic ulceration in patients who underwent off-loading treatment, compared to the group of patients who were not relieved of mechanical pressure on the ulcer.