Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing.

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1ß, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

HydroTac-a hydro-responsive wound dressing: a review of the in vitro evidence.

AIM: The aim of this review is to identify and summarise the key in vitro evidence available to support the use of HydroTac (HRWD-2) to address specific aspects associated with the treatment of both acute and hard-to-heal wounds. BACKGROUND: The provision of a moist wound healing environment to support optimal wound healing has been a basic tenet in wound care since the pioneering work on the benefits of occlusion to support wound healing. Modern wound dressings have adopted the benefits of moist healing through their innovative development. HRWD-2 has been shown in clinical studies to enable and support good healing outcomes and the in vitro evidence in support of this dressing is presented in this article. METHOD: An online literature search (supplemented with a manual search of resources not available online) was conducted to identify articles and studies describing in vitro evidence in support of HRWD-2 in aspects important for promoting a healing response in the clinical environment. RESULTS: In vitro studies showed that HRWD-2 contributes to balancing moisture levels and enhances the availability of growth factors known to be important for re-epithelialisation. Pre-clinical studies indicate that HRWD-2 enhances wound re-epithelialisation. Together these results suggest that HRWD-2 promotes a moist healing environment leading to the dressing supporting re-epithelialisation. In vitro data indicating an intrinsic lower in vitro adherence of HRWD-2 likely translate clinically to the benefits of an atraumatic wound dressing, including reduced pain (specifically at dressing change). CONCLUSION: The in vitro evidence presented in this review supports the successful clinical results reported for HRWD-2 in terms of fluid management, wound healing and pain reduction at dressing change.

Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm2 . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.

Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes.

OBJECTIVE: This study assesses a novel dressing concept in venous leg ulcer (VLU) patients. It is based on boosting endogenous growth factor activities synthesised by functional granulation tissue. METHODS: Patients received treatment for eight weeks with a hydrated polyurethane-containing foam dressing plus concomitant compression therapy. Wound area reduction (WAR), percentage of wounds achieving a relative WAR of ≥40% and ≥60%, wound pain ratings for the last 24 hours and at dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and safety parameters were recorded. RESULTS: There were 128 patients who received treatment and data for 123 wound treatment courses were documented. Wound area size decreased from 13.3±9.8cm2 to 10.5±12.2cm2 at week eight and median relative WAR was 48.8%. At week eight, a relative WAR ≥40% was reached by 54.5% of the wounds, 41.5% reached a relative WAR of ≥60% and complete healing was observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before dressing change) declined significantly from 30 to 15.5 (100 visual analogue scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p≤0.0001). The EQ-5D VAS rating increased from 58.4±19.2mm to 63.1±19.1mm (p=0.0059). CONCLUSION: This clinical assessment shows that the concept of boosting endogenous growth factors through hydrated polyurethanes has the potential to accelerate WAR in VLU patients while decreasing pain levels and improving quality of life parameters.

Safety and performance evaluation of a next-generation antimicrobial dressing in patients with chronic venous leg ulcers.

The objective of this study was to investigate the safety and performance of AQUACEL™ Ag+ dressing, a wound dressing containing a combination of anti-biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL™ Ag+ dressing, followed by management with AQUACEL™ wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL™ Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non-treatment-related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL™ Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.

Isolated retroperitoneal mixed germ cell tumor presenting as acute abdomen - case report.

Extragonadal germ cell tumors are an uncommon clinical entity. Their prevalence varies between 1 and 5% of all germ cell tumors. Approximately 85-90% of cases have metastatic changes at the time of diagnosis. In our article we would like to present a case of an 18-year-old patient who was admitted to the hospital due to acute abdominal symptoms. A day earlier, the patient suffered blunt abdominal trauma during workout. Post-traumatic changes, which were described after admission in computed tomography, intraoperatively proved to be masses of extraperitoneal tumor.

Conclusions from an Observational Study of Patients with Vascular Diseases Using the FMSF Technique.

Purpose: There is great demand for a diagnostic tool for non-invasive assessment of vascular circulation and metabolic regulation. Assessing both these functions is crucial, as each can have a distinct response to hypoxia. Patients and Methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for analysis of vascular circulation and metabolic regulation. In this observational study, the FMSF technique was used to diagnose patients with various vascular diseases. The study group consisted of 482 patients (264 females and 218 males) between the ages of 40-94 years with various vascular problems (arterial hypertension, cardiovascular disease, diabetes, hypercholesterolemia, and chronic venous disease). Results: Three major FMSF parameters were used: Ischemic Response (IRmax), Hyperemic Response (HRmax), and Reactive Hyperemia Response (RHR). All three parameters were found to decrease with age with a distinguishable kinetics. The IRmax parameter was used for characterization of metabolic reaction to transient hypoxia and HRmax was used for characterization of macrocirculatory function. Both were sex-dependent. Conclusion: Females were metabolically less adaptive to transient hypoxia than males. However, macrocirculatory function was better in females than among males. Microcirculatory function decreases gradually with age, while macrocirculatory function decreases much more slowly with age, with a tendency to stabilize after 70 years of age.

A prospective, multi-centre, randomised, open label, parallel, comparative study to evaluate effects of AQUACEL® Ag and Urgotul® Silver dressing on healing of chronic venous leg ulcers.

This study compared wound healing efficacy of two silver dressings, AQUACEL(®) Ag and Urgotul(®) Silver, against venous ulcers at risk of infection, over 8 weeks of treatment. The primary objective was to show non inferiority of AQUACEL(®) Ag to Urgotul(®) Silver. Patients (281) were randomised into two groups. The AQUACEL(®) Ag group had 145 patients treated with AQUACEL(®) Ag for 4 weeks followed by AQUACEL for another 4 weeks. TheUrgotul(®) Silver group had 136 patients treated with Urgotul(®) Silver for 4 weeks followed by Urgotul(®) for another 4 weeks. In both groups, ulcer size and depth, safety events and ulcer healing were compared. After 8 weeks of treatment, the AQUACEL(®) Ag group had a relative wound size reduction (49·65% ± 52·53%) compared with the Urgotul(®) Silver group (42·81% ± 60·0%). The non inferiority of the AQUACEL(®) Ag group to the Urgotul(®) Silver group was established based on the difference between them (6·84% ± 56·3%, 95% confidence interval -6·56 to 20·2) and the pre-defined non inferiority margin (-15%). Composite wound healing analysis showed that the AQUACEL(®) Ag group had statistically higher percentage of subjects with better wound progression (66·9% versus 51·9%, P = 0·0108). In general, both dressings were effective at promoting healing of venous ulcers.

Efficacy and Safety of a Hyaluronic Acid-Containing Gauze Pad in the Treatment of Chronic Venous or Mixed-Origin Leg Ulcers: A Prospective, Multicenter, Randomized Controlled Trial.

INTRODUCTION: Hyaluronic acid (HA)-containing formulations routinely are utilized along with standard therapy to promote faster healing of chronic wounds; evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. OBJECTIVE: This study compared the efficacy and safety of an HA-impregnated gauze pad with an identical gauze pad without HA in the treatment of chronic leg ulcers of vascular origin. MATERIALS AND METHODS: A prospective, multicenter, multinational, parallel-group, randomized, double-blind, clinical study was conducted between June 13, 2017, and December 31, 2018. Adults with 1 or more chronic leg ulcers of venous or mixed origin between 2 months and 4 years' duration were eligible to participate. Participants were randomized to treatment consisting of standard care (ie, ulcer cleansing, debridement/anesthesia as necessary, and optimized compression) and either application of a gauze pad containing 0.05% HA or a neutral comparator once daily for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed by 1 independent and experienced assessor blinded with respect to the treatment applied, as shown on digital photographs taken under standardized conditions at or before 20 weeks and confirmed 3 weeks later). Secondary efficacy endpoints included the percentage of completely healed target ulcers, residual area of target ulcer relative to baseline, the condition of the periulcerous skin, the total amount of analgesics used, the incidence of infection at the ulcer site of the target ulcer, patient adherence to treatment, time to achieve complete healing as centrally assessed, and pain intensity as measured by a visual analog scale. RESULTS: Among the 168 participants (82 in the HA gauze pad group and 86 in the neutral gauze pad group), 33 (39.8%) in the HA group experienced complete healing of the target ulcer, which was significantly higher than the neutral comparator group (15, 18.5%; P = .002). Results in the full analysis and per-protocol sets were consistent with the primary results; no significant difference was noted in outcomes when participants' wounds were stratified according to baseline ulcer size. CONCLUSIONS: HA delivered in a gauze pad formulation could be a beneficial treatment for chronic leg ulcers of venous or mixed origin.

Efficacy and Safety of a Hyaluronic Acid-Containing Cream in the Treatment of Chronic, Venous, or Mixed-Origin Leg Ulcers: A Prospective, Multicenter Randomized Controlled Trial.

INTRODUCTION: Topical applications of hyaluronic acid (HA)-containing formulations, based on the complex and vital role of HA in all stages of the wound-healing process, are routinely used with standard therapy to promote faster healing of chronic wounds. However, evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. OBJECTIVE: This study compared the efficacy and safety of topical application of a hyaluronic acid cream vs a neutral comparator (identical cream without HA) in treating subjects with chronic leg ulcers of vascular origin. MATERIALS AND METHODS: This was a prospective, multicenter double-blind randomized controlled trial. One hundred sixty-eight subjects with chronic leg ulcers of venous or mixed (venous and arterial) origin were randomized to receive either topical applications of 0.2% HA cream or neutral comparator cream for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed at 20 weeks or before and confirmed 3 weeks later). In both groups, topical treatment was associated with standard therapy (ulcer cleansing and optimized compression). RESULTS: The proportion of subjects with centrally assessed complete healing of the target ulcer that was confirmed 3 weeks later (primary efficacy endpoint) was substantially higher in the HA cream group (31.3%) than in the neutral cream group (14.8%; P =.009). Results in the full analysis, per protocol, and as assessed by the investigator were consistent with primary results. No significant difference in treatment effect was observed when subjects were stratified according to baseline ulcer size (≤20 cm2 or >20 cm2) regardless of topical treatment. Safety and tolerability were comparable between treatments. CONCLUSIONS: Treatment of subjects with chronic leg ulcers of venous or mixed origin with HA cream is safe, well tolerated, and results in a higher rate of healing than a neutral comparator cream.

Patients' satisfaction with therapy methods of advanced chronic venous disease.

BACKGROUND: To assess patients' satisfaction from the therapy of advanced chronic venous disorders (CVD) in everyday clinical practice in Poland, and to compare the efficacy of various venoactive drugs (VADs) in venous ulcers healing process. METHODS: Seven hundred and eighty unselected adult patients with active (N.=441) or healed (N.=339) venous ulcers participated in the non-interventional observational 6-week study. RESULTS: Compression therapy and VADs were utilized by 81.5% and 89.2% of patients respectively: 31.2% of all patients underwent surgical procedures for vein incompetence, 61.3% were satisfied with surgical methods, 43% with compression therapy, and 32.6% with VADs ­ with highest rate of satisfied patients in the group taking Ruscus aculeatus and HMC and ascorbic acid (51.4%). Of 377 patients with active venous ulcers smaller than 200 cm2, adherent to VADs, 18.0% have been cured, and 66.6% have improved during 6-week period of observation. Multiple logistic regression analysis revealed that the compression therapy (OR=2.74), the size of ulcer ≤10 cm2 (OR=2.70) were increasing the change of ulcer healing. No VADs was better than another in the healing process. CONCLUSION: 1) Compression therapy and VADs are highly utilized by patients with advanced CVD. 2) Patients are more satisfied with surgical than conservative treatment of advanced CVD. 3) More than half of the patients with the advanced stage CVD taking Ruscus aculeatus and HMC and ascorbic acid is satisfied with the obtained improvement. 4) Ruscus aculeatus and HMC and ascorbic acid is similarly effective as other frequently used VADs in venous ulcer healing. 5) Ruscus aculeatus and HMC and ascorbic acid exerting effects on veins, capillaries and lymphatic vessels may explain the positive results observed in this study.

Scintigraphic and ultrasonographic assessment of the effect of lumbar sympathectomy upon chronic arteriosclerotic ischaemia of lower extremities.

The aim of the study was an evaluation of the effect of onesided lumbar sympathectomy in patients with peripheral vascular disease of lower extremity(ies), using perfusion scintigraphy with (99)mTc-MIBI and ultrasound Doppler blood flow-rate measurements. A secondary aim was a comparison of the diagnostic efficacy of the two techniques applied. The study was performed on 30 patients, studied prior to and early after one-sided lumbar sympathectomy. The scintigraphy yielded results indicating a statistically significant increase in perfusion of femoral and calf muscles (p < 0.001). Ultrasound investigation demonstrated significant (p < 0.001) increase of the maximal blood flow rate in the popliteal artery. Scintigraphic perfusion study yielded better agreement with the clinical evaluation than the ultrasound Doppler technique (83 v. 47 per cent, p < 0.01) and higher sensitivity in demonstration of improved blood supply (88 v. 36 per cent, p < 0.001).

The own method and program of isotope quantitatively assessment of perfusion in muscles of upper limbs (initial report).

BACKGROUND: The issue of blood flow in muscles has been dealt with for many years. However, most often it was assessed qualitatively with standard vascular examinations. The quantitatively perfusion assessment is indispensable in the normal and pathological conditions. Some diseases impair the perfusion mainly in the area of upper limbs. It can be observed in Raynaud's disease, vascular occlusive diseases, neurological disturbances, and thermal injuries. Hyperhidrosis of upper limbs after sympathectomy of thoracic part of sympathetic trunk may bring closer the diagnosis statement. Nuclear medicine has the markers and methods that allow for the assessment of the volume of perfusion in muscles. The aim for creating this method and program was the development of radioisotope method allowing for quantitative assessment of perfusion in muscles of upper limbs. This should lead to calculating the perfusion index and its range of normal values in a greater group of patients and to using this method both in the healthy and pathological conditions. MATERIAL AND METHODS: 20 patients, age 30.4 ± 7.1 years, who underwent following examinations: qualification to the group, medical history, subject examinations, USG of upper limb vessels, anthropometric examinations, biochemical and hormonal blood tests, the assessment of upper limbs with USG Doppler and FMD (flow mediated dilatation), radioisotope examinations with gamma camera BrightView XCT by own program RAPUL (Radioisotope Assessment Perfusion of Upper Limb). Acquisitions were started five minutes after intravenous injection of 99mTc-MIBI (metoxyisobutylnitrite). The whole body scintigram and scintigrams of arm and forearm muscles in A-P projections were taken. RESULTS: In the examined patients, the results of anthropometric, biochemical and hormonal test were within the range of normal values. In radioisotope quantitative assessment of perfusion, perfusion indexes of left arm were 20 < PI(_left) < 11.90 and of the right arm 7.00 < PI(_right) <12.30. The dependency correlation PI(_left) vs. PI(_right) was strong r = 0.92036.The values of perfusion symmetry index (IPS) had a normal distribution and were within the following range: 0.9231 < IPS < 1.1019. CONCLUSIONS: The RAPUL method and program allow for quantitative assessment of perfusion in muscles of upper limbs. Developed program has a high repeatability of results. The results in the bigger group will allow for defining the range of normal values of perfusion index in muscles of upper limbs at rest. These will be diagnostically used both in healthy (sports medicine, military services) and pathological conditions.