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Histologic Outcomes With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From An Efficacy and Safety Study of Vedolizumab Intravenous Compared to Adalimumab Subcutaneous in Participants With Ulcerative Colitis (VARSITY).
Peyrin-Biroulet, L, Loftus, EV, Colombel, JF, Danese, S, Rogers, R, Bornstein, JD, Chen, J, Schreiber, S, Sands, BE, Lirio, RA
Gastroenterology. 2021;(4):1156-1167.e3
Abstract
BACKGROUND AND AIMS VARSITY (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis) showed superior clinical remission and endoscopic improvement in ulcerative colitis with vedolizumab vs adalimumab. This analysis compared histologic outcomes. METHODS Patients in VARSITY were randomized 1:1 to maintenance with vedolizumab IV 300 mg every 8 weeks or adalimumab SC 40 mg every 2 weeks (both following standard induction). Geboes Index and Robarts Histopathology Index (RHI) scores were used to assess prespecified histologic exploratory end points of histologic remission (Geboes <2 or RHI ≤2) and minimal histologic disease activity (Geboes ≤3.1 or RHI ≤4) at weeks 14 and 52. RESULTS In total, 769 patients received vedolizumab (n = 383) or adalimumab (n = 386). Mean baseline histologic disease activity was similar between vedolizumab and adalimumab groups. Vedolizumab induced greater histologic remission than adalimumab at week 14 (Geboes: 16.7% vs 7.3%, Δ9.4% [95% confidence interval {CI}, 4.9%-13.9%], P < .0001; RHI: 25.6% vs 16.1%, Δ9.5% [95% CI, 3.8%-15.2%], P = .0011) and week 52 (Geboes: 29.2% vs 8.3%, Δ20.9% [95% CI, 15.6%-26.2%], P < .0001; RHI: 37.6% vs 19.9%, Δ17.6% [95% CI, 11.3%-23.8%], P < .0001) overall and in both anti-tumor necrosis factor (TNF)-naïve and -failure subgroups. Results were similar for minimal histologic disease activity. Histologic outcomes were generally better in anti-TNF-naïve vs -failure patients. At week 52, rates of mucosal healing (composite end point of histologic plus endoscopic improvement) were also higher with vedolizumab than adalimumab (Geboes: 25.6% vs 6.7%; RHI: 30.5% vs 14.5%). CONCLUSIONS Higher rates of histologic remission, minimal histologic disease activity, and combined histologic plus endoscopic outcomes were observed with vedolizumab than with adalimumab in ulcerative colitis in both anti-TNF-naïve and -failure subgroups. REGISTRATION ClinicalTrials.gov NCT02497469; EudraCT 2015-000939-33.
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Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis.
Brandenburg, VM, Sinha, S, Torregrosa, JV, Garg, R, Miller, S, Canals, AZ, Bahr, D, Joubert, PH, Salcedo, C, Carroll, KJ, et al
Journal of nephrology. 2019;(5):811-821
Abstract
BACKGROUND Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification. METHODS In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations. RESULTS Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related. CONCLUSIONS SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.
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Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes.
Mikosiński, J, Kotala, M, Stücker, M, Twardowska-Saucha, K, Bonnekoh, B, Pańczak, K, Aleksiejew-Kleszczyński, T, Dissemond, J, Eming, SA, Kaspar, D, et al
Journal of wound care. 2018;(9):608-618
Abstract
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.
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Maltodextrin/ascorbic acid stimulates wound closure by increasing collagen turnover and TGF-β1 expression in vitro and changing the stage of inflammation from chronic to acute in vivo.
Salgado, RM, Cruz-Castañeda, O, Elizondo-Vázquez, F, Pat, L, De la Garza, A, Cano-Colín, S, Baena-Ocampo, L, Krötzsch, E
Journal of tissue viability. 2017;(2):131-137
Abstract
It has been reported that carbohydrates confer physicochemical properties to the wound environment that improves tissue repair. We evaluated in vitro and in vivo wound healing during maltodextrin/ascorbic acid treatment. In a fibroblast monolayer scratch assay, we demonstrated that maltodextrin/ascorbic acid stimulated monolayer repair by increasing collagen turnover coordinately with TGF-β1 expression (rising TGF-β1 and MMP-1 expression, as well as gelatinase activity, while TIMP-1 was diminished), similar to in vivo trends. On the other hand, we observed that venous leg ulcers treated with maltodextrin/ascorbic acid diminished microorganism population and improved wound repair during a 12 week period. When maltodextrin/ascorbic acid treatment was compared with zinc oxide, almost four fold wound closure was evidenced. Tissue architecture and granulation were improved after the carbohydrate treatment also, since patients that received maltodextrin/ascorbic acid showed lower type I collagen fiber levels and increased extracellular alkaline phosphatase activity and blood vessels than those treated with zinc oxide. We hypothesize that maltodextrin/ascorbic acid treatment stimulated tissue repair of chronic wounds by changing the stage of inflammation and modifying collagen turnover directly through fibroblast response.
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Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?
Wiegand, C, Bittenger, K, Galiano, RD, Driver, VR, Gibbons, GW
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2017;(5):871-882
Abstract
Noncontact low-frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 as well as PF4, TGF-beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL-8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E5 was found compared to < 10E5 , levels of IL-1beta, IL-8, and TNF-alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro-inflammatory cytokines as well as by reducing the overall bacterial burden.
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Control of post-hemorrhoidectomy symptoms and wound healing by Triclosan: a randomized, double-blind, controlled trial.
Giannini, I, Pecorella, G, Pennisi, D, Santangelo, G, Digennaro, R, Latorre, F, Giuliani, G, Altomare, DF
Minerva chirurgica. 2014;(2):75-82
Abstract
AIM: Milligan-Morgan hemorrhoidectomy (MM) is still the most common treatment for grades III and IV hemorrhoids despite prolonged post-operative anal pain and wound healing. This multicenter, double blind, randomized, controlled trial was designed to assess the safety and the efficacy of anal wound cleansing with Triclosan (Proctocid®) in the control of symptoms and healing time after MM. METHODS A total of 113 patients with grades III and IV hemorrhoids, undergoing open hemorroidectomy by diathermy or Ligasure vessel sealing device, were randomly assigned to Triclosan or sodium hypochlorite solution. All patients received analgesics and a fiber-rich diet after hemorrhoidectomy. Postoperative anal pain, bleeding and/or secretion and itch were assessed 7, 14 and 21 days after hemorrhoidectomy by a Visual Analogue Scale (VAS) and the day of complete re-epithelialization of anal wounds was recorded. RESULTS Fifty-five patients were randomized for Triclosan treatment and 58 for the control drug. The two groups were comparable for demographics, severity of hemorrhoids and technique used for the hemorrhoidectomy. The comparison of days to get complete anal wound healing shows a trend of significance (P=0.05) for the Triclosan group. Bleeding and/or secretion, anal pain and itch were significantly better (P=0.003; P<0.0001 and P=0.01, respectively). CONCLUSION Triclosan solution for the treatment of post-hemorrhoidectomy wounds is safe and improves the control of post-operative symptoms and wound healing time compared to sodium hypochlorite.
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[Effects of nutrition intervention for pressure ulcer patients--healing rate and speed of wound size and nutrition--].
Ohura, T, Nakajo, T, Okada, S, Omura, K, Adachi, K, Oishi, S
Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics. 2013;(3):377-83
Abstract
UNLABELLED The objective of this multicenter open-label randomized study was for evaluating nutrition intervention on pressure ulcer healing. Tube-fed patients with Stages III to IV pressure ulcers were enrolled. Target energy levels to be given were the same value as at the time of enrollment or BEE×1.1 (activity factor)×1.1-1.3 (stress factor) in the control group, and BEE×1.1×1.3-1.5 in the intervention group. Both groups received the feeding formula Racol(®) for 12 weeks, and were prescribed to have pressure relief mattresses, and to unify the repositioning method, treatment drugs, and wound dressing materials. Ulcer sizes (length×width), nutritional state, and adverse events were evaluated. RESULTS OF THE STUDY Energy levels administered to the control (n=29) and intervention (n=21) groups were 29.1±4.9 (mean±SD) and 37.9±6.5 kcal/kg/day, respectively. Regarding pressure ulcer size, the interaction between the nutrition intervention and the courses during observational weeks was significant (P<0.001). Similarly, significant differences were observed with weight, waist circumference, Cu (P<0.001), suprailiac skinfold thickness (P<0.01), thigh circumference, and prealbumin (P<0.05), but not with the incidence of adverse events (P=0.360). Principal component analysis indicated remarkable decreases in ulcer size and improvement rates of waist circumference and suprailiac skinfold thickness in the intervention group. Covariance structure analysis showed that nutrition intervention has a direct effect on reduction in ulcer size. The results suggested that aggressive nutrient intervention accelerated the pressure ulcer of wound healing process and had a direct effect on reduction in ulcer size.
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[Effect of Yunnan Baiyao capsules on the socket healing of impacted mandibular third molar extraction].
Zhang, K, Wang, X, Zhang, W, Zhao, JZ, Dong, H
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology. 2012;(4):199-202
Abstract
OBJECTIVE To investigate the effect of the traditional Chinese medicine Yunan Baiyao on the socket healing of impacted mandibular third molar extraction. METHODS A total of 200 patients requiring extractions of impacted mandibular wisdom teeth were randomized into the treatment group and the control group in a double-blinded manner, and Yunan Baiyao capsules or placebo capsules (2 g/d) were orally administered for 28 days after the operation. Dental quantitative CT scan was performed, and the volume and density of new bone at the extraction site were measured two month after operation. RESULTS A total of 188 patients completed the study. No adverse events related to the medication occurred. The volume of new bone was (477.39 ± 166.47) mm(3) in the treatment group and (442.65 ± 143.58) mm(3) in the control group, which was not significantly different between the two groups. The density of new bone was (296.90 ± 37.94) mg/cm(3) in the treatment group and (298.54 ± 40.21) mg/cm(3) in the control group, which was not significantly different between the two groups. The number of the teeth root, the impacted conditions, whether or not retainning the alveolar septum, suturing soft tissues of the extraction site and blood clot formation within 1 week after operation were significantly correlated with the volume of new bone. CONCLUSIONS Yunnan Baiyao capsules has no effect on the volume and density of new bone at the extraction site two months after operation following extractions of impacted mandibular third molars.
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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.
Harding, K, Gottrup, F, Jawień, A, Mikosiński, J, Twardowska-Saucha, K, Kaczmarek, S, Sopata, M, Shearman, C, Pieronne, A, Kommala, D
International wound journal. 2012;(3):285-94
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Abstract
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.
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The use of superoxidized aqueous solution versus saline as a replacement solution in the versajet lavage system in chronic diabetic foot ulcers: a pilot study.
Bowling, FL, Crews, RT, Salgami, E, Armstrong, DG, Boulton, AJ
Journal of the American Podiatric Medical Association. 2011;(2):124-6
Abstract
BACKGROUND The removal of necrotic tissue from chronic wounds is required for wound healing to occur. Hydrodebridement (jet lavage) and superoxidized aqueous solution have been independently used for debriding wounds. We sought to investigate the use of superoxidized aqueous solution with a jet lavage system. METHODS Twenty patients with diabetic foot ulcers were randomly assigned in a 1:1 ratio to receive jet lavage debridement with either superoxidized aqueous solution or standard saline weekly. RESULTS There was no significant difference between the two treatments in the reduction of bacterial load or wound size in 4 weeks. No adverse reactions were reported for either treatment. CONCLUSIONS The use of superoxidized aqueous solution for jet lavage debridement seemed to be as safe and effective as saline. Future investigations should concentrate on whether superoxidized aqueous solution may reduce the bacterial air contamination associated with hydrodebridement.