Small is beautiful: why profundaplasty should not be forgotten

BACKGROUND: Surgical profundaplasty (SP)is used mainly as an adjunct to endovascular management of peripheral vascular disease (PAD) today. Results from earlier series of profundaplasty alone have been controversial, especially regarding its hemodynamic effect. The question is: Can profundaplasty alone still be useful? Our aim was to evaluate its role in the modern management of vascular patients. METHODS: This was a retrospective outcome study. A consecutive series of 97 patients (106 legs) from January 2000 through December 2003 were included. In 55 (52%) legs, the superficial femoral artery was occluded. These patients were included in the current analysis. Of these patients 14 (25%) were female. Mean age was 71 ((11) years. Nineteen (35%) were diabetic. The indication for operation was claudication in 29 (53%), critical leg ischemia (CLI) in 26 (47%), either with rest pain in 17 (31%), or ulcer/gangrene in 9 (16%). Endarterectomy with patch angioplasty with bovine pericardium was performed in all cases. Mean follow-up was 33 ( 14 months. Mean preoperative ankle brachial index (ABI) was 0.6. Sustained clinical efficacy was defined as upward shift of 1 or greater on the Rutherford scale without repeat target limb revascularization (TLR) or amputation. Mortality, morbidity, need for TLR, or amputation were separate endpoints. RESULTS: Postoperatively, ABI was significantly improved (mean = 0.7), in 24 (44%) by more than 0.15. At three years, cumulative clinical success rate was 80%. Overall, patients with claudication had a better outcome than those with CLI (p = 0.04). Two (4%) major amputations and 2 (4%) minor ones were performed, all in patients with CLI. None of the 9 (16%) ulcers healed. CONCLUSION: Profundaplasty is still a valuable option for patients with femoral PAD and claudication without tissue loss. It is a straightforward procedure that combines good efficacy with low complication rates. Further endovascular treatment may be facilitated. It is not useful for patients with the combination of critical ischemia and tissue loss.

The "flap-shaft" prosthesis for insensate feet with Chopart or Lisfranc amputations

BACKGROUND: The inevitable detachment of tendons and the loss of the forefoot in Chopart and Lisfranc amputations result in equinus and varus of the residual foot. In an insensate foot these deformities can lead to keratotic lesions and ulcerations. The currently available prostheses cannot safely counteract the deforming forces and the resulting complications. METHODS: A new below-knee prosthesis was developed, combining a soft socket with a rigid shaft. The mold is taken with the foot in the corrected position. After manufacturing the shaft, the lateral third of the circumference of the shaft is cut away and reattached distally with a hinge, creating a lateral flap. By closing this flap the hindfoot is gently levered from the varus position into valgus. Ten patients (seven amputations at the Chopart-level, three amputations at the Lisfranc-level) with insensate feet were fitted with this prosthesis at an average of 3 (range 1.5 to 9) months after amputation. The handling, comfort, time of daily use, mobility, correction of malposition and complications were recorded to the latest followup (average 31 months, range 24 to 37 months after amputation). RESULTS: Eight patients evaluated the handling as easy, two as difficult. No patient felt discomfort in the prosthesis. The average time of daily use was 12 hours, and all patients were able to walk. All varus deformities were corrected in the prosthesis. Sagittal alignment was kept neutral. Complications were two minor skin lesions and one small ulcer, all of which responded to conservative treatment, and one ulcer healed after debridement and lengthening of the Achilles tendon. CONCLUSIONS: The "flap-shaft" prosthesis is a valuable option for primary or secondary prosthetic fitting of Chopart-level and Lisfranc-level amputees with insensate feet and flexible equinus and varus deformity at risk for recurrent ulceration. It provided safe and sufficient correction of malpositions and enabled the patients to walk as much as their general condition permitted.

Effect of risk factors on complicated and uncomplicated ulcers in the TARGET lumiracoxib outcomes study

BACKGROUND ; AIMS: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups. METHODS: Patients with osteoarthritis (age, >or=50 y) were randomized to receive lumiracoxib 400 mg once daily, naproxen 500 mg twice daily, or ibuprofen 800 mg 3 times daily for 12 months. Events were categorized by a blinded adjudication committee. The primary end point was all definite or probable ulcer complications. RESULTS: For patients taking NSAIDs, factors associated with an increased risk of ulcer complications were age 65 years or older (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.48-3.59), previous history of gastrointestinal bleed or ulcer (HR, 3.61; 95% CI, 1.86-7.00), non-Caucasian racial origin (HR, 2.10; 95% CI, 1.35-3.27), and male sex (HR, 1.70; 95% CI, 1.08-2.68). With lumiracoxib, significant risk factors were age 65 years or older (HR, 3.18; 95% CI, 1.40-7.20), male sex (HR, 2.60; 95% CI, 1.25-5.40), non-Caucasian racial origin (HR, 2.16; 95% CI, 1.02-4.59), and concomitant aspirin use (HR, 2.89; 95% CI, 1.40-5.97). Increased risks in patients age 65 years and older were increased further if other risk factors were present. Lumiracoxib maintained an advantage over NSAIDs across all subgroups except aspirin use. CONCLUSIONS: Lumiracoxib was associated with a reduced risk of ulcer complications compared with NSAIDs in all significant subgroups except aspirin users.

Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia

This study evaluated the efficacy and safety of intramuscular administration of NV1FGF, a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 (FGF-1), versus placebo, in patients with critical limb ischemia (CLI). In a double-blind, randomized, placebo-controlled, European, multinational study, 125 patients in whom revascularization was not considered to be a suitable option, presenting with nonhealing ulcer(s), were randomized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1, 15, 30, and 45 (total 16 mg: 4 x 4 mg). The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25. Secondary end points included ankle brachial index (ABI), amputation, and death. There were 107 patients eligible for evaluation. Improvements in ulcer healing were similar for use of NV1FGF (19.6%) and placebo (14.3%; P = 0.514). However, the use of NV1FGF significantly reduced (by twofold) the risk of all amputations [hazard ratio (HR) 0.498; P = 0.015] and major amputations (HR 0.371; P = 0.015). Furthermore, there was a trend for reduced risk of death with the use of NV1FGF (HR 0.460; P = 0.105). The adverse event incidence was high, and similar between the groups. In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo.

[Case report of osteo-odonto keratoprosthesis (Strampelli) and of Dacron keratoprosthesis (Pintucci)]

BACKGROUND: In severe forms of ocular surface disorders keratoprostheses provide the ultimate possibility to restore vision. They are made of an optical cylinder integrated with a supporting biocompatible or biological haptic. CASE REPORT: We report on two patients with different types of keratoprostheses. An 88-year-old woman with ocular pemphigoid received in 1970 a bilateral osteo-odonto-keratoprosthesis (Strampelli). A 59-year-old man with refractory corneal ulcer after corneal grafting received in 2003 a keratoprosthesis with supporting Dacron tissue (Pintucci). RESULTS: The course 35 years after implantation of the osteo-odonto-keratoprosthesis was uneventful. Histologically there were no signs of loosening, rejection or infection. The autologous dentin, which was used for the fixation, was still present. The eye with the Dacron fixated prosthesis (Pintucci) had to be enucleated due to a loosening with endophthalmitis one and a half year after implantation. CONCLUSIONS: Keratoprostheses with autologous fixation often show good long-term results. On the other hand, prostheses with synthetic material are more often complicated by dislocation and inflammation.

In search of optimal compression therapy for venous leg ulcers: a meta-analysis of studies comparing diverse [corrected] bandages with specifically designed stockings

OBJECTIVE: In search of an optimal compression therapy for venous leg ulcers, a systematic review and meta-analysis was performed of randomized controlled trials (RCT) comparing compression systems based on stockings (MCS) with divers bandages. METHODS: RCT were retrieved from six sources and reviewed independently. The primary endpoint, completion of healing within a defined time frame, and the secondary endpoints, time to healing, and pain were entered into a meta-analysis using the tools of the Cochrane Collaboration. Additional subjective endpoints were summarized. RESULTS: Eight RCT (published 1985-2008) fulfilled the predefined criteria. Data presentation was adequate and showed moderate heterogeneity. The studies included 692 patients (21-178/study, mean age 61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9 years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks. Patient and ulcer characteristics were evenly distributed in three studies, favored the stocking groups in four, and the bandage group in one. Data on the pressure exerted by stockings and bandages were reported in seven and two studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P < .00001). The average time to healing (seven studies, 535 patients) was 3 weeks shorter with stockings (P = .0002). In no study performed bandages better than MCS. Pain was assessed in three studies (219 patients) revealing an important advantage of stockings (P < .0001). Other subjective parameters and issues of nursing revealed an advantage of MCS as well. CONCLUSIONS: Leg compression with stockings is clearly better than compression with bandages, has a positive impact on pain, and is easier to use.

[HPV type 16-associated anal intraepithelial neoplasia (AIN)]

A 25-year-old woman had suffered from a perianal ulcer for approximately 1 year. Topical and systemic treatments had been unsuccessful. Employing virologic and histologic techniques, we confirmed the diagnosis of an intraepithelial neoplasia. Anal intraepithelial neoplasia (AIN) is induced by carcinogenic human papillomaviruses. It can occur anywhere in the anogenital area. Because of its frequency, AIN is a crucial differential diagnosis for lesions of the anogenital area region failing to respond to standard therapies.

Results of herd health management in veal calf production

The aim of this study was to document experience gained with herd health management in veal calf production and to describe the calves' most frequent health problems. Fifteen farms with an 'all-in-all-out' animal flow system and 20 farms with a continuous animal flow system were investigated and data on animal movements, housing, feeding, medical treatments, and management were collected. Cadavers underwent pathological examination, and data were recorded from the carcasses of slaughtered calves. On the 15 'all-in-all-out'-farms, 2'747 calves were clinically examined by the contract-veterinarian upon arrival at the farm, and 71,1 % of the calves showed at least one sign of illness. The main causes of death were with 54,9 % digestive disorders (a perforating abomasal ulcer being the most frequent diagnosis), followed by respiratory diseases (29,6 %, mainly pneumonia). The meat color of 25 % of the carcasses was red. Calves from farms with the continuous animal flow system, which recruit mainly animals originating from the same farm, showed significantly better results regarding antibiotic use, performance and carcass quality than those calves from farms with the 'all-in-all-out'-system.

Lameness and foot lesions in Swiss dairy cows: II. Risk factors.

The objective of this study was to evaluate risk factors associated with foot lesions and lameness in Swiss dairy cows. Potential risk factors were recorded by means of examination of 1'449 Swiss cows and the management systems of 78 farms during routine claw-trimming, and during personal interviews with the associated farmers. Statistical analysis of animal-based and herd level risk factors were performed using multivariate logistic regression models. The risk of being lame was increased in cows affected by digital dermatitis complex, heel-horn erosion, interdigital hyperplasia, Rusterholz' sole ulcer, deep laceration, double sole and severe hemorrhages. Cleanliness, BCS, affection with other foot lesions, breed, importance of claw health to the farmer, frequency of routine claw-trimming, producing according to the guidelines of the welfare label program RAUS, and silage feeding were shown to be associated with the occurrence of some of the evaluated foot lesions and lameness. The identified risk factors may help to improve management and the situation of lameness and claw health in dairy cows in Switzerland and other alpine areas with similar housing and pasturing systems.

Lesions of the gastric mucosa in adult horses of different disciplines: a review

The prevalence of gastric mucosal lesions in the thoroughbred race horse has been the subject of numerous studies. The frequency of gastric ulcer diseases in the adult horse of other sport disciplines are less well investigated. Recent data show that gastric mucosal lesions in non thoroughbred racehorses occur considerably more frequently than previously thought. Prevalences of up to 93 % in endurance horses, of up to 87 % in standardbreds, of 40 % in western horses, of 63 % in show-jumping horses, of 71 % in broodmares and of 53 % in leisure horses are reported. Since the introduction of gastroscopy in equine medicine in the 1990s, numerous scoring-systems to describe the number, the severity and the localisation of the lesions have been used. Unfortunately, no standardized scoring system is generally accepted to date. A direct comparison of results from different studies is therefore difficult. Comparison and interpretation of data is further hampered by the heterogenicity of the study populations which consist of horses of different age-groups, breeds and exercise intensity.

The development and characterization of two types of chronic responses in irradiated mouse colon

The hypothesis to be tested is that there are two distinct types of chronic responses in irradiated normal tissues, each resulting from damage to different cell populations in the tissue. The first is a sequala of chronic epithelial depletion in which the tissue's integrity cannot be maintained, i.e. a "consequential" chronic response. The other response is due to cell loss in the connective tissue and/or vascular stroma, i.e. a "primary" chronic response. The purpose of this study was to test the hypothesis in the murine colon by first, establishing a model of each chronic response and then, by determining whether the responses differed in timing of expression, histology, and expression of specific collagen types. The model of late damage used was colonic obstructions/strictures induced by a single dose of 27 Gy ("consequential" response) and two equal doses of 14.75 Gy (t = 10 days) ("primary" response). "Consequential" lesions appeared as early as 5 weeks after 27 Gy and were characterized by a deep mucosal ulceration and a thickened fibrotic serosa containing excessive accumulations of collagen types I and III. Both types were commingled in the scar at the base of the ulcer. Fibroblasts were synthesizing pro-collagen types I and III mRNA 10 weeks prior to measurable increases in collagen. A significant decrease in the ratio of collagen types I:III was associated with the "consequential" response at 4-5 months post-irradiation. The "primary" response, on the other hand, did not appear until 40 weeks after the split dose even though the total dose delivered was approximately the same as that for the "consequential" response. The "primary" response was characterized with an intact mucosa and a thickened fibrotic submucosa which contained excessive amounts of only collagen type I. An increased number of fibroblasts were synthesizing pro-collagen type I mRNA nearly 25 weeks before collagen type I levels were increased. The "primary" response lesion had a significantly elevated collagen type I:III ratio at 10-13 months post-irradiation. These data show a clear difference between the two chronic response and suggest that not all chronic responses share a common pathogenesis, but depend on the cell population in the tissue that is damaged. ^

Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm(®) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622).

BACKGROUND Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. OBJECTIVE We conducted the first clinical trial with the novel PlasmaDerm(®) VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. METHODS From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak(®) , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). RESULTS The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm(®) VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.

Factors influencing the attitudes of cattle veterinarians, farmers, and claw trimmers towards the pain associated with the treatment of sole ulcers and the sensitivity to pain of dairy cows

This study assessed the attitudes of personnel involved in therapeutic claw trimming of dairy cattle in Switzerland towards pain associated with sole ulcers and their treatment. Data from 77 farmers, 32 claw trimmers, and 137 cattle veterinarians were used. A large range of factors were associated with whether the respondents thought that anaesthesia during the treatment of sole ulcers was beneficial; these included year of graduation, work experience, attitude to costs of analgesia, perception of competition between veterinarians and claw trimmers, estimation of pain level associated with treatment, estimated sensitivity of dairy cows to pain, knowledge of the obligation to provide analgesia, and whether the respondent thought lesion size and occurrence of defensive behaviour by the cow were important. Respondents' estimation of the pain level associated with sole ulcer treatment was linked to frequency of therapeutic claw trimming, age, farmers' income, estimated knowledge of the benefits of analgesia, and estimated sensitivity of dairy cows to pain. The latter factor was associated with profession, frequency of therapeutic claw trimming, capability of pain recognition, opinion on the benefits of analgesia, knowledge of the obligation to provide analgesia, and self-estimation of the ability to recognise pain. Improving the knowledge of personnel involved in therapeutic claw trimming with regard to pain in dairy cows and how to alleviate it is crucial if management of pain associated with treatment of sole ulcer and the welfare of lame cows are to be optimised.

Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease.

Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a necrotizing disease of the skin and subcutaneous tissue, which is most prevalent in rural regions of West African countries. The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of antibiotic therapy. Nevertheless, scarring and permanent disabilities occur frequently and Buruli ulcer still causes high morbidity. A vaccine against the disease is so far not available but would be of great benefit if used for prophylaxis as well as therapy. In the present study, vesicular stomatitis virus-based RNA replicon particles encoding the M. ulcerans proteins MUL2232 and MUL3720 were generated and the expression of the recombinant antigens characterized in vitro. Immunisation of mice with the recombinant replicon particles elicited antibodies that reacted with the endogenous antigens of M. ulcerans cells. A prime-boost immunization regimen with MUL2232-recombinant replicon particles and recombinant MUL2232 protein induced a strong immune response but only slightly reduced bacterial multiplication in a mouse model of M. ulcerans infection. We conclude that a monovalent vaccine based on the MUL2232 antigen will probably not sufficiently control M. ulcerans infection in humans.

Aortic morphometry at endograft position as assessed by 3D image analysis affects risk of type I endoleak formation after TEVAR

PURPOSE The purpose of this study was to identify morphologic factors affecting type I endoleak formation and bird-beak configuration after thoracic endovascular aortic repair (TEVAR). METHODS Computed tomography (CT) data of 57 patients (40 males; median age, 66 years) undergoing TEVAR for thoracic aortic aneurysm (34 TAA, 19 TAAA) or penetrating aortic ulcer (n = 4) between 2001 and 2010 were retrospectively reviewed. In 28 patients, the Gore TAG® stent-graft was used, followed by the Medtronic Valiant® in 16 cases, the Medtronic Talent® in 8, and the Cook Zenith® in 5 cases. Proximal landing zone (PLZ) was in zone 1 in 13, zone 2 in 13, zone 3 in 23, and zone 4 in 8 patients. In 14 patients (25%), the procedure was urgent or emergent. In each case, pre- and postoperative CT angiography was analyzed using a dedicated image processing workstation and complimentary in-house developed software based on a 3D cylindrical intensity model to calculate aortic arch angulation and conicity of the landing zones (LZ). RESULTS Primary type Ia endoleak rate was 12% (7/57) and subsequent re-intervention rate was 86% (6/7). Left subclavian artery (LSA) coverage (p = 0.036) and conicity of the PLZ (5.9 vs. 2.6 mm; p = 0.016) were significantly associated with an increased type Ia endoleak rate. Bird-beak configuration was observed in 16 patients (28%) and was associated with a smaller radius of the aortic arch curvature (42 vs. 65 mm; p = 0.049). Type Ia endoleak was not associated with a bird-beak configuration (p = 0.388). Primary type Ib endoleak rate was 7% (4/57) and subsequent re-intervention rate was 100%. Conicity of the distal LZ was associated with an increased type Ib endoleak rate (8.3 vs. 2.6 mm; p = 0.038). CONCLUSIONS CT-based 3D aortic morphometry helps to identify risk factors of type I endoleak formation and bird-beak configuration during TEVAR. These factors were LSA coverage and conicity within the landing zones for type I endoleak formation and steep aortic angulation for bird-beak configuration.