Improve Ulcer Healing Research Articles

Superficial venous surgery as a management for chronic venous leg ulcers

Background Venous leg ulcer (VLU) is a chronic problem affecting thousands of patients annually. The aims of this study were to evaluate the effectiveness of saphenous vein surgery as a management for chronic VLUs and to determine which group of patients will gain more benefit from surgery.Patients and methods A prospective study was conducted over a period of 4 years on 40 patients (32 males and eight females) with chronic VLUs CEAP 6 (indicating skin changes with active ulceration) and isolated superficial venous system insufficiency. Patients were divided into two groups: group A included 20 patients who underwent compression alone and group B included 20 patients for whom surgery on the superficial saphenous system was performed followed by compression. The patients were followed up for ulcer healing rate, healing time, and incidence of recurrence for at least 12 months.Results The rate of ulcer healing was 65% in group A within 14–24 weeks and 100% in group B within 8–16 weeks. The recurrence rates were 30% in group A and 10% after surgical correction in group B within 12 months of follow-up.Conclusion Surgical correction of incompetent superficial saphenous veins improves ulcer healing rate, healing time, and reduces recurrence in patients with isolated superficial venous system incompetence.

Evidence-based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans.

Evidence-based ulcer care guidelines detail optimal components of care for treatment of ulcers of different etiologies. We investigated the impact of providing specific evidence-based ulcer treatment components on healing outcomes for lower limb ulcers (LLU) among veterans in the Pacific Northwest. Components of evidence-based ulcer care for venous, arterial, diabetic foot ulcers/neuropathic ulcers were abstracted from medical records. The outcome was ulcer healing. Our analysis assessed the relationship between evidence-based ulcer care by etiology, components of care provided, and healing, while accounting for veteran characteristics. A minority of veterans in all three ulcer-etiology groups received the recommended components of evidence-based care in at least 80% of visits. The likelihood of healing improved when assessment for edema and infection were performed on at least 80% of visits (hazard ratio [HR] = 3.20, p = 0.009 and HR = 3.54, p = 0.006, respectively) in patients with venous ulcers. There was no significant association between frequency of care components provided and healing among patients with arterial ulcers. Among patients with diabetic/neuropathic ulcers, the chance of healing increased 2.5-fold when debridement was performed at 80% of visits (p = 0.03), and doubled when ischemia was assessed at the first visit (p = 0.045). Veterans in the Pacific Northwest did not uniformly receive evidence-based ulcer care. Not all evidence-based ulcer care components were significantly associated with healing. At a minimum, clinicians need to address components of ulcer care associated with improved ulcer healing.

Autologous bone marrow mononuclear cell implantation therapy is an effective limb salvage strategy for patients with severe peripheral arterial disease

This study was conducted to determine if intramuscular and intra-arterial stem cell injections delay or prevent major limb amputations, improve ankle-brachial index measurements, relieve rest pain, and improve ulcer healing. A prospective case series with interventions occurring between December 2007 and September 2012 and a 3-month minimum follow-up was conducted at an urban tertiary care referral hospital. Patients with severe limb-threatening peripheral arterial disease, without other options for revascularization, were eligible for enrollment. Dual intramuscular and intra-arterial injection of bone marrow mononuclear cells harvested from the iliac crest was performed. Major limb amputation at 3 months was the primary outcome measure. Secondary outcome measures included ankle-brachial index measurements, rest pain, and ulceration healing. Kaplan-Meier survivorship was performed to ascertain overall survivorship of the procedure. No complications related to the procedure were reported. Of 49 patients (56 limbs) enrolled, two patients (two limbs) died, but had not undergone major amputation, and five limbs (8.9%) underwent major amputation within the first 3 months. Three-month follow-up evaluations were conducted on the remaining 49 limbs (42 patients). Median postprocedure revised Rutherford and Fontaine classifications were significantly lower compared with median baseline classifications. After 3 months, seven patients (nine limbs) died but had not undergone major amputation, and seven limbs (14.3%) underwent major amputation. At a mean follow-up of 18.2 months, the remaining 33 limbs (29 patients) had not undergone a major amputation. Freedom from major adverse limb events (MALE) was 91.1% (95% confidence interval, 79.9-96.2) at 3 months and 75.6% (95% confidence interval, 59.4-86.1) at 12 months. This procedure was designed to improve limb perfusion in an effort to salvage limbs in patients for whom amputation was the only viable treatment option. The results of this analysis indicate that it is an effective strategy for limb salvage for patients with severe peripheral arterial disease.

Cell Therapy for Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials.

Early-phase trials showed the feasibility and potential efficacy of cell therapy in patients with critical limb ischemia (CLI). For systematic review, randomized controlled trials (RCTs) of cell therapy versus no cell therapy in CLI were searched from PubMed and the Cochrane library databases. Outcome measures included major amputation, complete ulcer healing, ankle-brachial index (ABI), and all-cause mortality. Data were pooled using 16 RCTs, involving 774 patients. Compared with no cell therapy, cell therapy significantly reduced major amputation (odds ratio [OR]: 0.54; 95% CI: 0.34-0.87:P= .01) and improved ulcer healing (OR: 2.90; 95% confidence interval [CI]: 1.44-5.82;P< .01) and ABI (OR: 5.91; 95% CI: 1.85-18.86:P< .01). Peripheral blood-derived mononuclear cells (PB-MNCs; OR: 0.29; 95% CI: 0.12-0.72;P< .01) and bone marrow concentrate (OR: 0.44; 95% CI: 0.21-0.93;P= .03) significantly lowered the risk of major amputation. The PB-MNCs also significantly increased ulcer healing (OR: 5.77; 95% CI: 1.77-18.87;P< .01). All-cause mortality was similar in both groups (OR: 0.78; 95% CI: 0.44-1.40;P= .41). However, all estimates were nonsignificant following reanalysis using placebo-controlled RCTs only. Cell therapy remains a potential therapeutic option in CLI, but further larger placebo-controlled RCTs are needed.

Lipid-lowering Therapy in the Diabetic Foot: Seeing the Whole Iceberg and not Just the Tip

Diabetic foot ulcers arise from neuropathy and/or ischaemia. The diabetic foot is associated with cardiovascular disease (CVD) and excess mortality. Lipid-lowering therapy reduces CVD morbidity and mortality in diabetic patients with foot ulcers. In particular, statins decrease CVD mortality and improve survival in diabetic foot patients, while fibrates benefit patients with a specific lipid profile. Statins reduce progression of the local disease, improving symptoms and reducing amputations, mainly due to their impact on peripheral arterial disease. Fibrates appear to reduce amputations by improving neuropathy. They also improve ulcer healing and reduce recurrence. This review assesses the role of hypolipidaemic treatment in diabetic foot patients.

Diabetic foot disease and oedema

Diabetic foot ulcers (DFUs) are common and disabling, giving rise to significant morbidity and mortality as well as worldwide socioeconomic problems. Despite treatment, DFUs readily become chronic wounds and may lead to major lower limb amputations. The pathogenesis of DFUs is complex and the main aetiologies are peripheral neuropathy, ischaemia from peripheral arterial disease and biomechanical abnormalities. Microvascular disease is also a significant problem for people with diabetes and contributes to foot ulceration. Successful management of DFUs consists of debridement, infection control, the use of offloading appliances and revascularisation where necessary. Foot ulcers are usually associated with infection and inflammation which lead to surrounding oedema of the foot. Standard offloading devices such as total contact casts and removable cast walkers do not actively reduce foot oedema. There is promising evidence that active oedema reduction by intermittent pneumatic compression in the diabetic foot improves ulcer healing. The objective of this article is to review the association of foot oedema and DFUs, including the role of appliances which reduce oedema. The information presented is vital to those involved in the management of DFUs.

Venous Ulcer: Review Article

Venous ulceration is the most severe and debilitating outcome of chronic venous insufficiency in the lower limbs and accounts for 80 percent of lower extremity ulcerations. The morbidity caused by them has a serious impact on the quality of life. Sustained venous hypertension, caused by venous insufficiency leads to venous ulceration. The diagnosis is mainly clinical but needs to be differentiated from other causes of lower limb ulcers. Doppler ultrasound is the diagnostic investigation. Treatment options for venous ulcers include conservative management, mechanical treatment, medications, and surgical options. The goals of treatment are to reduce edema, improve ulcer healing, and prevent recurrence. The achievement of good long term results depends on continuous care, ulcer care clinics, home health nursing and regular evaluation by the doctor. They have a crucial role to play for the amelioration of this common and morbid condition.

Antibacterial Effect of Autologous Platelet-Rich Gel Derived from Subjects with Diabetic Dermal Ulcers In Vitro

Background. Autologous platelet-rich gel (APG) is an effective method to improve ulcer healing. However, the mechanisms are not clear. This study aimed to investigate the antibacterial effect of APG in vitro. Methods. Platelet-rich plasma (PRP), platelet-poor plasma (PPP) and APG were prepared from whole blood of sixteen diabetic patients with dermal ulcers. Antibacterial effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were evaluated by bacteriostasis assay of APG, PRP, and APG-APO (APG combined with apocynin), with phosphate-buffered saline (PBS) and PPP as the control group. Results. (1) Compared to the PBS and PPP, the APG and APG-APO groups showed strong antibacterial activity against Staphylococcus aureus. There was no significant difference (P > 0.05) between APG and APG-APO. (2) Compared to PBS, APG, APG-APO, and PRP showed obvious antibacterial effects against Escherichia coli and Pseudomonas aeruginosa. No significant difference (P > 0.05) was revealed among the three groups. Compared to the PPP group, they did not show antibacterial effect against Escherichia coli and Pseudomonas aeruginosa (P > 0.05). Conclusions. APG has antibacterial effect against Staphylococcus aureus mediated by platelet activation in the diabetic patients with dermal ulcer, and does not present obvious antibacterial effect against Escherichia coli or Pseudomonas aeruginosa. Combination of APG and antibiotics may have synergistic antibacterial effect.

Subcutaneous fasciotomy and eradication of superficial venous reflux for chronic and recurrent venous ulcers: mid-term results

Increased intramuscular and subcutaneous tissue pressures are often found in patients with severe chronic venous insufficiency venous ulcer disease. Additional subcutaneous para-tibial fasciotomy promotes early ulcer healing. This study evaluates the mid-term effect of eradication of superficial reflux with additional fasciotomy in patients with increased tissue pressures. Between January 2006 and June 2009, 58 patients underwent fasciotomy. Tissue pressures (intramuscular and subcutaneous) were measured. Sixty-nine limbs with 91 venous ulcers were treated. Mean duration of the venous ulcer was 3.4 years. Underlying disease was post-thrombotic syndrome (PT) in 19 patients (33%, 24 limbs, 27 ulcers) and non-post-thrombotic (non-PT) severe chronic venous insufficiency in 39 (67%, 45 limbs, 64 ulcers). All patients were C6 at the time of surgery. Preoperative tissue pressures were 23.5 ± 6.1 mmHg (intramuscularly) and 9.8 ± 3.2 mmHg (subcutaneously). Ninety ulcers (99%) healed postoperatively (42 with and 48 without skin grafting). Tissue pressures significantly decreased following surgery and remained low at three months postoperatively. Ten ulcers in six patients recurred six to 20 months postoperatively (11%), resulting in 86.4 actuarial freedom from venous ulcer recurrence at three years following surgery. Four patients (1 non-PT and 3 PT) had re-fasciotomy; all healed initially but two ulcers (2 patients, PT) recurred at 11 and 12 months. Those patients underwent re-fasciotomy, one healed and one recurred six months later. Eradication of superficial reflux with additional subcutaneous fasciotomy for chronic and recurrent venous ulcer improves ulcer healing or success of skin grafting. Mid-term results are excellent particularly in patients with non-PT disease. Recurrence is more frequently seen in patients with PT syndrome. In patients with ulcer recurrence and high tissue pressures, re-fasciotomy can be helpful to promote healing, particularly in patients with primary venous disease.

Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb Ischemia

Background— Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Methods and Results— Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm 2 to 1.89±3.5 cm 2 [ P =0.014] versus placebo, 2.92±3.5 cm 2 to 2.89±4.1 cm 2 [ P =0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [ P =0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [ P =0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups. Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage ( r =0.8; P &lt;0.001). Conclusions— Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00282646.

Hyperbaric oxygen therapy improves health‐related quality of life in patients with diabetes and chronic foot ulcer

Adjunctive treatment with hyperbaric oxygen therapy has recently been shown to improve ulcer healing in patients with chronic diabetic foot ulcer. The aim of the present study is to evaluate whether hyperbaric oxygen therapy improves the health related quality of life in these patients. Prospective randomized placebo-controlled double-blinded study setting using SF-36. A total of 75 patients were included in the study; 38 were randomized to hyperbaric oxygen therapy and 37 to placebo (hyperbaric air). The overall mean physical and mental summary scores for the entire study population at baseline were 29.6 ± 8.8 and 47.5 ± 12.4, respectively. There was a significant difference between baseline and 1 year follow-up responses to the mental summary score and two of the eight (SF-36) (?) domains in the -hyperbaric oxygen group, whereas no significant improvement of health related quality of life was seen in the placebo group. Comparing quality of life in patients who healed their ulcer (healers) with those who did not (non-healers), post-treatment levels of the mental health summary score, social functioning and role limitations due to physical and emotional health were significantly improved in healers. No differences were seen in any SF-36 (?) domain in non-healers. Hyperbaric oxygen therapy improves long-term health related quality of life in patients with chronic diabetic foot ulcers, possibly attributable to better ulcer healing.

Transcutaneous oxygen tension: a useful predictor of ulcer healing in critical limb ischaemia

To investigate the threshold of transcutaneous oxygen tension (TcPO(2)) values in predicting ulcer healing in patients with critical limb ischaemia in a prospective study. 50 patients suffering from critical limb ischaemia with chronic ischemic ulcers or gangrenous toes were enrolled in this study between January and December 2008. Their demographic data and ankle brachial pressure index (ABPI) were collected. Baseline ulcers were measured with a wound measurement system (Visitrak, Smith & Nephew). TcPO(2) was measured at rest in the supine position and with 30 degrees leg elevation. The patients with infective and ischemic ulcers underwent debridement and gangrenous toes were amputated. Ulcer outcome was classified as either: (1) A healing ulcer, showing good epithelialisation or granulation at both base and edges, or a decrease in ulcer area during the study; or (2) A non-healing ulcer, showing poor granulation tissue formation or a pale base and necrotic edges, or deterioration in an ischaemic ulcer. The mean age of the patients was 67.6 + or - 10.8 years. The most common risk factor was hypertension (90%). Mean ABPI was 0.75 + or - 0.39. 13 patients (26%) had a TcPO(2) of less than 20 mmHg, of which none showed any improvement in ulcer healing (p<0.001). 15 patients (30%) had a TcPO(2) of more than 40 mmHg, of which all progressed to complete ulcer healing (p<0.001). In the borderline group (20-40 mmHg, 22 patients, 44%), 10 patients (45%) had a TcPO2 drop of <10 mmHg with 30 degrees leg elevation, of which 8 achieved complete ulcer healing (p<0.001). 12 patients (55%) had a TcPO(2) drop of >10 mmHg with 30 degrees leg elevation, of which 11 showed no ulcer healing (p<0.001). TcPO(2) measurement is an accurate, non-invasive, and good predictor of ischemic ulcer healing, for cut-off TcPO(2) values of less than 20 mmHg and more than 40 mmHg. In addition, the leg elevation method for TcPO(2) might provide an important adjunct in the assessment of patients with borderline values.

Pro‐ulcer effects of resveratrol in mice with indomethacin‐induced gastric ulcers are reversed by l‐arginine

Although resveratrol is currently being evaluated in pre-clinical studies as a potential cancer chemopreventive agent and cardiovascular stress-releasing compound, treatment with resveratrol severely delays healing of pre-existing gastric ulcers. Resveratrol treatment can also induce endothelial NOS (eNOS) expression. Here, we have attempted to modulate NO production via eNOS in order to alleviate the pro-ulcer effects of resveratrol. Gastric ulcers were induced in mice with a single dose of indomethacin. The effects of pretreatment with l-arginine on the pro-ulcer effects of resveratrol in these mice were then assessed. We measured ulcer damage scores (DS), myeloperoxidase (MPO) activity, generation of prostaglandin E(2) (PGE(2)) and NO, along with a gene expression study. Resveratrol significantly aggravated damage from indomethacin-induced gastric ulcers, and delayed healing, as shown by increased DS and MPO activity. The mRNA for cyclooxygenase (COX)-1, but not that for COX-2, was inhibited by resveratrol treatment, with reduced synthesis of PGE(2) by gastric tissue. However, resveratrol treatment induced eNOS gene expression and shifted the eNOS/iNOS balance. l-Arginine given before resveratrol in mice with indomethacin-induced ulcers significantly increased tissue NO synthesis and improved ulcer healing. Exogenous l-arginine increased NO formation via raised levels of eNOS induced by resveratrol and protected against the pro-ulcer effects of resveratrol. Therefore, l-arginine might be useful for alleviation of the pro-ulcer side effects of resveratrol in patients.

Improvement in Healing and Reduction in HIV Shedding with Episodic Acyclovir Therapy as Part of Syndromic Management among Men: A Randomized, Controlled Trial

It is uncertain whether episodic acyclovir will enhance ulcer healing if delivered at primary health care settings, because there is often a delay in treatment initiation. A double-blind, randomized, placebo-controlled trial of 5-day acyclovir (400 mg 3 times daily) was conducted among men with genital ulcers in South Africa. Participants received syndromic management; were tested for ulcer etiology, human immunodeficiency virus (HIV), syphilis, and herpes simplex virus type 2 (HSV-2); and were seen over the course of a month to evaluate ulcer healing and HIV-1 RNA shedding. Outcomes were ulcer duration and HIV-1 RNA shedding, assessed on day 7 among HIV-1-seropositive participants with a herpetic ulcer. A total of 309 men received acyclovir, and 306 received placebo; 63% were HIV-1 positive. There were 295 HIV-1-positive participants with a herpetic ulcer. Acyclovir improved ulcer healing--61% of those receiving acyclovir healed by day 7, compared with 42% of those receiving placebo (adjusted relative risk, 1.4 [95% confidence interval, 1.1-1.8]; P= .003). Acyclovir also improved healing by a median of 3 days (P= .002) and reduced HIV-1 ulcer shedding on day 7 (24% for acyclovir vs 37% for placebo; P= .05). Addition of acyclovir to syndromic management will improve healing of genital ulcers and may potentially reduce HIV transmission in combination with other interventions.

Impact of Acyclovir on Genital and Plasma HIV‐1 RNA, Genital Herpes Simplex Virus Type 2 DNA, and Ulcer Healing among HIV‐1–Infected African Women with Herpes Ulcers: A Randomized Placebo‐Controlled Trial

Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 (HIV-1). Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a randomized, double-blind, placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days. Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction (PCR). Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 (HSV-2) DNA and plasma HIV-1 RNA were quantitated by real-time PCR. Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers (54 of whom were given acyclovir and 64 of whom were given placebo). Acyclovir had little impact on (1) detection of cervicovaginal HIV-1 RNA (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.8-1.2) at day 7 of treatment, (2) the mean cervicovaginal HIV-1 RNA load (-0.06 log(10) copies/mL; 95% CI, -0.4 to 0.3 log(10) copies/mL) at day 7 of treatment, or (3) the plasma HIV-1 RNA load (+0.09 log(10) copies/mL; 95% CI, -0.1 to 0.3 log(10) copies/mL) at day 14 of treatment. At day 7, women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA (RR, 0.70; 95% CI, 0.4-1.2) or cervicovaginal HSV-2 DNA (RR, 0.69; 95% CI, 0.4-1.3), had a lower quantity of HSV-2 DNA (-0.99 log(10) copies/mL; 95% CI, -1.8 to -0.2 log(10) copies/mL), and were more likely to have a healed ulcer (RR, 1.26; 95% CI, 0.9-1.9). Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing, but it did not decrease genital and plasma HIV-1 RNA loads. ClinicalTrials.gov identifier NCT00158483 .

The Influence of Helicobacter pylori Eradication on Leptin, Soluble CD40 Ligand, Oxidative Stress and Body Composition in Patients with Peptic Ulcer Disease

To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of soluble CD40 ligand, leptin, oxidative stress and body composition in patients with dyspepsia infected with H. pylori. The infection of H. pylori was based on the presence of both (14)C urea breath test (UBT) and histology. Patients were given triple eradication therapy for 14 days and at 3 months after the treatment, (14)C UBT was reinstituted. Fasting glucose, leptin, body composition, soluble CD40 ligand, total oxidant status (TOS) were studied before and at 3 months after the treatment. In 33 subjects, H. pylori infection was successfully eradicated. sCD40L, and TOS levels were significantly decreased after H. pylori eradication. The percentage of body fat and body fat mass significantly decreased whereas the fat free mass (FFM) increased after eradication. However, eradication of the organism yielded no differences in leptin levels. These findings suggest that H. pylori eradication reduces the sCD40L and oxidative stress, fat mass with a significant increase in fat free mass. Thus, eradication of H. pylori infection not only improves ulcer healing, but may also reduce the presumed atherosclerosis risk.

Abstract 6054: Immersing Feet in CO 2 -Rich Water-Bath Improves Ulcer Healing on Ischemic Limb after Infrainguinal Bypass Surgery

Background : We have shown that immersion of feet in warmed water enriched with carbon dioxide (CO 2 immersion) improves subcutaneous microcirculation in critical limb ischemia (CLI) with ischemic ulcer/gangrene. Using an animal model, other group has reported that the CO 2 immersion enhances collateral blood flow in ischemic limb via mobilization of endothelial progenitor cells and activation of NO-cGMP system. For CLI patients with ulcer/gangrene, infrainguinal bypass surgery is the standard therapy. However, ulcer healing and prevention of amputation still remain suboptimal. In order to know whether the CO 2 immersion improves the clinical efficacy, here we performed the CO 2 immersion after infrainguinal bypass surgery. Methods : This study was designed as a prospective controlled trial. Fifty-five patients with ischemic ulcer/gangrene underwent the standard care including successful infrainguinal bypass surgery were enrolled and were randomly divided into the two groups; patients underwent standard care added CO 2 immersion (CO 2 group, 27 patients with 30 limbs) and patients received standard care alone (control group, 28 patients with 30 limbs). The patients in the CO 2 group immersed their feet in CO 2 enriched water (depth of 20 –30 cm, 37–38°C, duration for 10 minutes) twice a day. Primary endpoint was defined as complete healing of ischemic ulcers. Results : Baseline demographical data, traditional risk factors, surgical procedure, ankle pressure and transcutaneous oxygen pressure (tcPO 2 ) were comparable between the two groups. Rate of the complete ulcer healing after 1-year was much higher in the CO 2 group than in the control group (43.3% vs. 20.0%, HR 2.72, 95%CI 1.03–7.17, p=0.043). Cox multivariate analysis revealed that CO 2 immersion (HR 4.13, 95%CI 1.09 –15.75, p=0.038), diabetes (HR 0.020, 95%CI 0.01–.303, p=0.005) and tcPO 2 (HR 1.04, 95%CI 1.00 –1.09, p=0.050) were independent predictors for complete ulcer healing. In contrast, rates of 1-year mortality, graft patency and limbs salvage showed no significant differences between 2 groups (p=0.55, p=0.47 and p=0.16, respectively). Conclusion : The CO 2 immersion after infrainguinal bypass surgery provided additional benefit for the ulcer healing in CLI patients with ulcer/gangrene.

Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L‐tryptophan in rats

Following induction of gastric ulcer in rats by serosal application of acetic acid, local mucosal necrosis ensues accompanied by a reduction in mucosal microcirculation and by almost immediate expression of inducible nitric oxide (NO) synthase (iNOS) and proinflammatory cytokines. Daily application of melatonin (20 mg/kg) or l-tryptophan (100 mg/kg) accelerates ulcer healing by affecting the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system with excessive production of protective PG, especially in later period of ulcer healing. Furthermore, expression of hypoxia inducible factor, vascular-endothelial growth factor, an activation of cNOS-NO system and the stimulation of sensory nerves with the expression and release of calcitonin gene related peptide (CGRP) appear to aid the restoration of mucosal repair and microcirculation in the ulcer bed. The enhanced expression of the melatonin MT(2) receptors (MT(2)-R) combined with overexpression of key enzymes involved in biosynthesis of melatonin such as N-acetyltransferase and hydroxyindole-O-methyltransferase contribute to the acceleration of ulcer healing by this indole. Melatonin-induced acceleration of ulcer healing is also mediated by release of gastrin and ghrelin, the most potent stimulants of gastric mucosal cell proliferation and mucosal repair. These sequential steps in ulcer healing accelerated by melatonin can be interfered with by the blockade of MT(2)R, COX-2/PG and cNOS/NO systems, and by reduction in the inflammatory iNOS/NO system. Thus, melatonin and its precursor l-tryptophan, trigger the cascade of molecular events leading to the functional improvement in ulcer healing.

Secondary chronic venous disorders

Secondary chronic venous disorders (CVD) usually follow an episode of acute deep venous thrombosis (DVT). Most occluded venous segments recanalize over the first 6 to 12 months after an episode of acute DVT, leading to chronic luminal changes and a combination of partial obstruction and reflux. Such morphological changes produce venous hypertension with the highest levels of ambulatory venous pressure occurring in patients with combined outflow obstruction and distal reflux. The clinical manifestations of secondary CVD, including pain, venous claudication, edema, skin changes, and ulceration are commonly referred to as the post-thrombotic syndrome. Such sequelae are best avoided by early and aggressive treatment of proximal DVT. The diagnostic evaluation of secondary CVD is similar to primary CVD and is based upon duplex ultrasound. However, the definition of hemodynamically significant venous stenosis remains obscure and there are no reliable tests to confirm the presence of such lesions. Diagnosis depends more on anatomic rather than hemodynamic criteria, and IVUS is superior to venography in estimating the morphological degree and extent of iliac vein stenosis. The fundamental role of compression in the treatment of CVD is well recognized. Compliance with compression is essential to heal ulcers and minimize recurrence. The efficacy of various adjuncts to ulcer treatment, including complex wound dressings and medications have been variable. Although superficial venous surgery has not been demonstrated to improve ulcer healing rates, it does decrease ulcer recurrence. Deep venous valve reconstruction is performed in only a few specialized centers, and the results are better for primary than for secondary CVD. Treatment of incompetent perforating veins remains controversial. Although artificial venous valves are promising, most early experimental models have failed. With respect to venous obstruction, iliocaval angioplasty and stenting has emerged as the primary treatment for proximal iliofemoral venous obstruction with surgical bypass assuming a secondary role.

Revisión sistemática del soporte nutricional en las úlceras por presión

Pressure ulcer is an area of localised damage to the skin and underlying tissue caused by pressure, shear, friction and/or combination of these things. Prevalence of this entity is between 3 and 66%, depending of the patients and the pathology. Pressure ulcer is associated with an increased risk of morbidity and mortality. One of the most important risk factors to develop a pressure ulcer is nutritional status. We can use different interventional strategies, first of all (primary intervention) before the patient has developed a ulcer and secondly, the treatment of established ulcer (secondary prevention). In the most important primary prevention study with 662 patients, two oral nutritional supplements per day were given to the patients. The incidence of pressure ulcer was 40% (118/295) in the interventional group and 48% (181/377) in control group. A relative risk to develop a pressure ulcer with supplementation of 0.83 (CI95%: 0.70 a 0.99). In the studies with secondary prevention, when we analyze in an individual way the different nutrients, zinc has not demonstrated the utility in an independent way. Vitamin C shows contradictory data in two randomized clinical trial with the same dose (500 mg each 12 hours). Recently, some randomized clinical trials have demonstrated an improvement in healing rates with enhanced enteral formulas (zinc, arginine, vitamin C). Oral supplementation without taking account micronutrients decreases risk of pressure ulcer. However, studies of secondary prevention due to heterogeneity have not let clear conclusions. However, enteral enhanced formula could improve ulcer healing.