A placebo-controlled, double-blind study of mesoglycan in the treatment of chronic venous ulcers.

OBJECTIVES: to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. METHODS: non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24+/-1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan-Meier method. RESULTS: One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm(2)in the mesoglycan group and 3.9 cm(2)in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p < 0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. CONCLUSIONS: treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns.     

Ranitidine in the treatment of gastric ulceration

Seventy-two patients with endoscopically proven gastric ulcers were entered into a prospective controlled trial to assess the efficacy of ranitidine and cimetidine in ulcer healing. All patients were biopsied on entry and at subsequent endoscopies. After exclusion of 7 patients during the first month of treatment, the remaining 65 patients, 47 males and 18 females, mean age 48.2 +/-1.5 years, at 1 month had a healing rate of 47% and 52% respectively. The non-healers continued their treatment for a further 4 weeks. This increased the healing rate to 77% and 76% respectively. If the defaulters and poor compliers are withdrawn the healing rate rises to 58% and 57% at 4 weeks and to 91% and 79% at 8 weeks respectively. There was no significant difference between the two groups as regarded initial ulcer size and severity of dyspepsia. Antacid tablet consumption during the study was comparable. The initial size of the ulcers which failed to heal after 4 weeks of treatment tended to be larger than those which healed (P less than 0.05), but smoking did not appear to influence ulcer healing. No obvious side-effects or evidence of dysplasia were found. The study shows that ranitidine is at least as effective as cimetidine in gastric ulcer healing.     

Hyaluronic acid dressing (Healoderm) in the treatment of diabetic foot ulcer: A prospective,randomized, placebo‐controlled,single‐center study

Fast and complete healing of a diabetic foot ulcer (DFU) is challenging due to the hostile wound healing environment of the diabetic patients. As a part of a multimodal treatment approach, advanced dressing material using hyaluronic acid (HA) has been found to be effective. However, previous studies have used HA with additional biologics, which interferes in determining the true clinical effect of HA in DFU. To examine the sole effectiveness of HA in DFU treatment, a prospective, randomized, placebo‐controlled, single‐center study was conducted using an HA dressing without additional substances. Thus, 34 patients who met the inclusion criteria were randomized into two groups (the study group: HA dressing material; the control group: conventional dressing material). During the 12‐week study period, complete ulcer healing rate was evaluated as a primary endpoint. Additionally, healing velocity and the mean duration for achieving a 50% ulcer size reduction was compared between the two groups as a secondary endpoint. At the end of the study, the study group presented a significantly higher complete healing rate as compared to that in the control group [84.6% (11/13), 41.6% (5/12), respectively, P = 0.041]. Additionally, faster ulcer healing velocity and shorter mean duration for achieving a 50% ulcer size reduction were observed in the study group (P = 0.022 and 0.004, respectively). The Kaplan‐Meier survival analysis for the median time for 50% ulcer healing rate also showed a significantly shorter duration in the study group (21 days vs. 39 days, P = 0.0127). Finally, there were no adverse events related to the dressing materials used in the study. As a major component of the extracellular matrix, this study supports the safety and efficacy of a pure HA dressing without additional substances in treating DFU.     

Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies

The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus becaplermin gel-30 microg/g, or good ulcer care plus becaplermin gel-100 microg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (相似文献   

Comparison of famotidine 40 mg with ranitidine 300 mg at night in short-term duodenal ulcer healing. A South African multicentre study

One hundred and thirty-two patients with endoscopically confirmed duodenal ulcers were entered into a 4-6-week double-blind trial of famotidine (Fm) and ranitidine (Rn). Seventy patients were randomised to Fm 40 mg at night and Rn placebo and 62 to Rn 300 mg at night and Fm placebo. Gelusil tablets were allowed for ulcer pain, and diary cards were issued. Clinical evaluations were carried out on entry and at 2 and 4 weeks, and endoscopy was repeated at 4 weeks. Patients with an unhealed ulcer at 4 weeks were continued on the same treatment for another 2 weeks and further endoscopy was carried out at 6 weeks. The groups were comparable with respect to age, sex, duration of the most recent attack, initial ulcer size and smoking, but the duration of disease tended to be longer in the Rn-treated group (P less than 0.05). Of the patients available for analysis, 75% of the Fm-treated and 78% of the Rn-treated patients were healed at 4 weeks and 91% of patients in both treatment groups were healed at 6 weeks. Gelusil consumption and symptomatic responses were comparable in the two groups, and no side-effects were noted apart from mild dizziness in 1 patient after a single Fm tablet. The mean initial size of ulcers healed at 4 weeks was significantly less than that of ulcers which were unhealed at 4 weeks (P less than 0.01), and the healing rate among smokers was significantly lower than that among non-smokers--48 of 72 patients (67%) and 41 of 45 (91%) respectively (P less than 0.01). The study shows that Fm 40 mg at night is as effective as Rn 300 mg in duodenal ulcer healing.     

The treatment of venous leg ulcers: a new therapeutic use of iloprost

BACKGROUND: We conducted a study using an intravenous (i.v.) infusion of iloprost in the treatment of venous ulcers to verify whether the association of i.v. iloprost + local therapy + elastic compression has a favorable effect when compared with traditional treatment with local therapy and elastic compression. STUDY DESIGN: We evaluated the effects of iloprost in 98 consecutive patients with noncomplicated venous ulcers of lower limbs subdivided into 2 groups: the first group (48 patients) received iloprost in saline solution for 3 weeks and the second group (50 patients) received a venous infusion of a saline solution. The patients were examined at baseline time 0 (first visit) and then after 15, 30, 45, 60, 75, 90, 105, 120, 135, and 150 days. RESULTS: In the first group, after 90 days, all the ulcers had healed, whereas in the second group only 50% of ulcers had healed after 105 days. At the end of the study, in the second group only 84.09% of ulcers had healed. The statistical analysis showed a significant difference between the first (iloprost group) and the second group (placebo group). Besides, in the first group the cicatrization of the ulcer happened in a shorter period (27.90% after 60 days; 41.86% after 75 days; and 100% after 100 days) whereas in the second group, at the end of the study, in 15.91% of patients the ulcers had not recovered. CONCLUSION: Iloprost can significantly reduce healing time for venous leg ulcers through several actions.     

Allogeneic keratinocyte for intractable chronic diabetic foot ulcers: A prospective observational study

Chronic diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are often difficult to treat. The application of newly developed dressing material in patients with chronic DFUs has been reported to be effective. The purpose of this study was to evaluate the usefulness of allogeneic keratinocyte treatment for chronic DFUs. We performed weekly allogeneic keratinocyte treatment for up to 12 weeks in 71 patients with intractable DFUs. We investigated healing rate, wound‐healing velocity, and time to 50% wound size reduction and analysed factors affecting ulcer healing. Fifty‐six patients (78.8%) had complete wound healing. Forty‐six patients (64.7%) showed complete healing within an average of 6.1 weeks, and 10 patients (14.1%) showed partial healing with an average 35.5% reduction vs initial size at the end of follow up. The 10 patients who showed partial healing continued to receive treatment after the 12‐week study period. The mean time to complete wound healing was 7.8 weeks. Fifteen patients (21.1%) experienced treatment failure because of infection, local necrosis, no change in ulcer size, or osteomyelitis during the follow‐up period. No adverse events were observed. Allogeneic keratinocyte treatment is effective for chronic, difficult‐to‐treat DFUs.     

Ulcer‐free survival days and ulcer healing in patients with diabetic foot ulcers: A prospective cohort study

Healing rates may not give a complete indication of the effectiveness and management of diabetic foot ulcers because of high recurrence rates. The most important outcome for patients is remaining ulcer‐free; however, this has hardly been investigated. The aim of our study was to prospectively investigate ulcer‐free survival days and ulcer healing in patients with diabetic foot ulcers. This was a prospective cohort study of all referrals to our diabetic foot expertise centre from December 2014 to April 2017. Outcomes were determined after a minimum follow‐up period of 12 months. Primary outcomes were ulcer‐free survival days and 12‐month healing percentages. Predictors for ulcer‐free survival days and healing were investigated in multivariate analyses. A total of 158 patients were included. Median ulcer‐free survival days in the healed group were 233 days (interquartile range [IQR] 121‐312) and 131 days (IQR 0–298) in the overall population. The healing rate at 12‐month follow up was 67% (106/158), and the recurrence rate was 31% (33/106). Independent predictors of ulcer‐free survival days were duration of diabetes, peripheral artery disease (PAD), cardiovascular disease, end‐stage renal disease (ESRD), and infection. Ulcer‐free survival days are related to PAD and cardiovascular disease, and ulcer‐free survival days should be the main outcome when comparing the effectiveness of management and prevention of the diabetic foot ulcers.     

腔内激光闭合术联合硬化剂在高原地区下肢静脉曲张患者中的治疗体会

目的 探讨腔内激光闭合术联合硬化剂在高原地区下肢静脉曲张患者中的治疗情况。方法 收集2019年4月至2021年10月在西藏自治区人民医院治疗的99例原发性下肢静脉曲张患者临床资料,所有患者均行单侧大隐静脉闭合术+泡沫硬化剂注射微创治疗,观察患者的围手术期指标、切口情况、大隐静脉闭合情况、复发情况及并发症发生情况。结果 术前合并溃疡者20例,比例为20.2%;术中出血量为10(10,20)ml;17例患者术中做了切口,切口比例为17.2%,切口长度为1(1,2)cm;平均住院时间（3.28±0.57）d;术后第7天、第1个月、第3个月、第6个月,均未出现伤口延迟愈合,其中术后第6个月随访时复发2例（2.02%）。结论 腔内激光闭合术联合硬化剂是治疗高原地区下肢静脉曲张患者的安全、彻底、有效的微创方式。     

A randomized trial of the Tubulcus multilayer bandaging system in the treatment of extensive venous ulcers

BACKGROUND: Venous ulcers are a major health problem because of their high prevalence and associated high cost of care. Compression therapy is the most widely used treatment for this condition. The vast majority of published articles on compression therapy present the results in the treatment of venous ulcers usually up to 15 to 20 cm(2). However, there are no published data in English medical literature on the efficacy of compression therapy in the treatment of extensive venous ulcers (ulcers >20 cm(2) of more than 6 months' duration) with regard to healing rate, time to healing, and recurrence rate at 12 months after healing. METHODS: A total of 138 patients with extensive venous ulceration (ulceration surface, 20-210 cm(2); duration, 7 months to 28 years) were randomized into 2 groups: (1) a treatment group (72 patients who were treated by using a multilayer bandaging system with the Tubulcus (a heelless open-toed elastic compression device knitted in tubular form) and elastic bandages and (2) a control group (66 patients treated with a multilayer bandaging system with elastic bandages only). The patients were treated on an ambulatory basis; the primary end point of the study was complete ulcer healing at 500 days. The secondary end point was to assess the ulcer recurrence rate during continuation of below-knee compression of different degrees of compression. In the treatment group, patients were instructed to continue to wear the Tubulcus (35 mm Hg), and patients in the control group were instructed to wear compression stockings with compression of 20 to 25 mm Hg. The exclusion criteria from the study were heart insufficiency with an ejection fraction <35, an ankle-brachial pressure index less than 0.8, and pregnancy. RESULTS: The cumulative healing rate was 93% in the treatment group and was 51% in the control group (P < .001). The median healing time in the treatment group was 133 days (range, 28 to 464 days), and in the control group it was 211 days (range, 61 to 438 days). The recurrence rate at 12 months in the treatment group was 24% (16/67) and was 53% (18/34) in the control group (P < .05). After additional compression treatment with the same treatment protocol, all 16 recurrent ulcers in the treatment group healed. In the control group, the healing rate of recurrent ulcers was 89% (16/18). CONCLUSIONS: This study suggests that for extensive venous ulceration, multilayer compression therapy with the Tubulcus provides an extremely high healing rate. Compression of more than 30 mm Hg results in decreased ulcer recurrence. However, recurrence cannot be completely avoided.     

Perforated peptic ulcer at the J.G. Strijdom Hospital. A retrospective study of 99 patients

This is a retrospective analysis of 99 patients with perforated peptic ulcer treated in the Department of Surgery at the J. G. Strijdom Hospital over a 6-year period. The incidence of this condition is increasing in our population. The mortality rate for perforated peptic ulcer remains high (12.1%). Forty-three per cent of our patients were suffering from a major medical illness at the time of perforation, with a mortality rate of 25.6%. The mortality rate for relatively fit patients was 1.8%. While more conservative surgery is indicated for high-risk patients, a definitive ulcer operation can be performed safely in patients who are not suffering from a major medical illness. Our selective operative policy is discussed.     

Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy

Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57. 5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers.     

Low-power HeNe laser treatment of venous leg ulcers.

Clinical observations have suggested that low-energy lasers, mainly helium-neon (HeNe) lasers, might stimulate wound healing. A controlled study of the effects of low-power HeNe laser was performed in conjunction with a standard treatment for healing chronic venous leg ulcers on 46 patients divided randomly into two groups. All patients received standard treatment (paste-impregnated bandage and a self-adhesive elastic bandage) plus either HeNe laser (wave-length, 632.8 nm; beam power, 6 mW; continuous emission, energy density, 4 J/cm2) or placebo HeNe laser twice weekly for 12 weeks. The areas of healing were examined and compared percentage-wise after 2, 4, 6, 8, and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the HeNe group compared with the placebo group.     

Measurement of the healing of venous ulcers.

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.     

Risk factors for delayed healing and recurrence of chronic venous leg ulcers--an analysis of 1324 legs.

OBJECTIVE: Despite similar disease patterns and treatment, there is great variation in clinical outcome between venous ulcer patients. The aim of this study was to identify independent risk factors for venous ulcer healing and recurrence. METHODS: Consecutive patients assessed by a specialist nurse-led leg ulcer service between January 1998 and July 2003 with an ABPI>0.85 were included in this study. Independent risk factors for healing and recurrence were identified from routinely assessed variables using a Cox regression proportional hazards model. RESULTS: A total of 1324 legs in 1186 patients were studied. The 24-week healing rate was 76% and 1 year recurrence rate was 17% (Kaplan-Meier life table analysis). Patient age (p <0.001, HR per year 0.989, 95% CI 0.984-0.995) and ulcer chronicity (p =0.019, HR per month 0.996, 95% CI 0.993-0.999) were independent risk factors for delayed ulcer healing. Ulcer healing time (p <0.001, HR per week 1.016, 95% CI 1.007-1.026) and superficial venous reflux not treated with surgery (p =0.015, HR 2.218, 95% CI 1.166-4.218) were independent risk factors for ulcer recurrence. CONCLUSIONS: Elderly patients with longstanding ulcers should be targeted for further research and may benefit from adjunctive treatments to improve clinical outcomes. Patients not treated with superficial venous surgery were at increased risk of leg ulcer recurrence.     

Venous leg ulcer: a meta-analysis of adjunctive therapy with micronized purified flavonoid fraction.

OBJECTIVE: To assess the effect of oral treatment with micronized purified flavonoid fraction (MPFF) on leg ulcer healing. DESIGN: Meta-analysis of randomised prospective studies using MPFF in addition to conventional treatment. MATERIALS AND METHODS: Five prospective, randomised, controlled studies in which 723 patients with venous ulcers were treated between 1996 and 2001 were identified. Conventional treatment (compression and local care) in addition to MPFF was compared to conventional treatment plus placebo in two studies (N = 309), or with conventional treatment alone in three studies (N = 414). The primary end point was complete ulcer healing at 6 months. RESULTS: At 6 months, the chance of healing ulcer was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone (RRR: 32%; CI, 3-70%). This difference was present from month 2 (RRR: 44%; CI, 7-94%), and was associated with a shorter time to healing (16 versus 21 weeks; P = 0.0034). The main benefit of MPFF was present in the subgroup of ulcers between 5 and 10 cm2 in area (RRR: 40%; CI, 6-87%), and those present for 6-12 months duration (RRR: 44%; CI, 6-97%). CONCLUSION: These results confirm that venous ulcer healing is accelerated by MPFF treatment. MPFF might be a useful adjunct to conventional therapy in large and long standing ulcers.     

Hyperbaric oxygen for the treatment of nonhealing arterial insufficiency ulcers

There is limited data regarding hyperbaric oxygen's effectiveness in the treatment of nonhealing arterial insufficiency ulcers. This study was designed to analyze healing rates and amputation rates in patients who underwent adjunctive hyperbaric oxygen for a nonhealing arterial insufficiency ulcer. A retrospective chart review was completed on patients who underwent hyperbaric oxygen for arterial insufficiency ulcers that failed to heal despite standard treatment. Information collected included complete ulcer healing, amputation, and patient characteristics. There were 82 patients identified. A majority did not have diabetes (84.1%). The overall rate of healing was 43.9%. The overall major amputation rate was 17.1%. The amputation rate among those who healed was 0% compared to 42.4% among those not healed (p < 0.0001). Dialysis was predictive of major amputation (p = 0.03). Our findings suggest hyperbaric oxygen can play a role in management of arterial insufficiency ulcers that have failed standard treatment. The overwhelming majority of these patients did not have diabetes, which allows this study to be translated to patients with a primary arterial insufficiency ulcer. These results support the use of hyperbaric oxygen for select nonhealing arterial insufficiency ulcers that have failed standard therapy and the need for a prospective pilot study.     

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming “skin islands”. The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.     

The use of a portable, wearable form of pulsed radio frequency electromagnetic energy device for the healing of recalcitrant ulcers: a case report

Pulsed radio frequency energy (PRFE) has successfully been used to treat diabetic and venous stasis ulcers. In this case report, a lightweight wearable form of a PFRE device was evaluated and used to treat three diabetic foot ulcers and one venous stasis ulcer. The ulcers were present on the four patients for more than 3 months and had failed to heal after conventional treatment. A lightweight battery-powered, wearable form of PRFE device was introduced as a treatment and used 6-8 hours per day for a period of 6 weeks. All patients after 1 week of therapy showed improvement and wound size was seen to decrease. Patient 1 had a venous stasis ulcer, and reported significant pain relief after 2 weeks treatment. Patients 2 and 3 achieved complete healing after 3 weeks treatment, and patients 1 and 4 had a 95% and 88% reduction in wound size, respectively, after the 6-week study period. Both these patients continued to complete healing using the PRFE device after the 6-week study period. PRFE treatment delivered in the form of a wearable lightweight patch appears to offer promise in the treatment of recalcitrant chronic wounds.