-
1.
Perianal Application of Glyceryl Trinitrate Ointment Versus Tocopherol Acetate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial.
Ruiz-Tovar, J, Llavero, C
Diseases of the colon and rectum. 2022;(3):406-412
Abstract
BACKGROUND Medical treatment, including glyceryl trinitrate ointment, represents the first step for the management of chronic anal fissure. However, glyceryl trinitrate ointment is associated with headache and, consequently, a high withdrawal rate of the treatment. OBJECTIVE The aim of the present study was to evaluate the effect of the topical application of tocopherol acetate ointment on pain relief and chronic anal fissure epithelialization, comparing it with the effect of a standard treatment with glyceryl trinitrate ointment. DESIGN This is a 2-parallel-group, single-center, randomized controlled, intent-to-treat clinical trial. SETTINGS This study was conducted at the Garcilaso Clinic affiliated with Universidad Alfonso X (Madrid, Spain). PATIENTS Patients with chronic anal fissure were selected. INTERVENTIONS Patients were randomly assigned into 2 groups: patients receiving tocopherol acetate ointment and patients receiving glyceryl trinitrate ointment. MAIN OUTCOME MEASURES The primary end point was quantification of anal pain 8 weeks after beginning the treatment as measured by a Visual Analogue Scale ranging from 0 to 100 mm. The secondary end points were the healing rate (during the treatment period of 8 weeks) and the recurrence rate. RESULTS One hundred sixty consecutive patients were treated, 80 in each group. By 8 weeks after treatment, mean anal pain score declined by 56.2 mm in the glyceryl trinitrate ointment group compared with a mean anal pain score decline of 67.1 mm in the tocopherol acetate ointment group (mean difference, 10.9 mm (95% CI, 4.3-18.6); p = 0.018). Sixteen weeks after finishing the therapy, the recurrence rate was 13.2% in the glyceryl trinitrate ointment group vs 2.9 in the tocopherol acetate ointment group (p = 0.031). LIMITATIONS Limitations of the study include the absence of manometric measurements of the internal anal sphincter before and after the treatments and the use of glyceryl trinitrate ointment as an active comparator, whereas calcium channel blockers are actually the standard treatment. CONCLUSIONS Anal pain was significantly lower in the tocopherol acetate ointment group than in the glyceryl trinitrate ointment group at 8 weeks after treatment. Tocopherol acetate ointment achieved a greater healing rate and a lower recurrence rate 16 weeks after finishing the treatment. See Video Abstract at http://links.lww.com/DCR/B751. REGISTRATION URL: https://www.clinicaltrials.gov; Identifier: NCT03787030.APLICACIÓN PERIANAL DE POMADA DE TRINITRATO DE GLICERILO FRENTE A LA POMADA DE ACETATO DE TOCOFEROL EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: UN ENSAYO CLÍNICO ALEATORIZADOANTECEDENTESEl tratamiento médico, incluida la pomada de trinitrato de glicerilo, representa el primer paso para el tratamiento de la fisura anal crónica. Sin embargo, la pomada de trinitrato de glicerilo se asocia con cefalea y, en consecuencia, una alta tasa de cancelación del tratamiento.OBJETIVOEl objetivo del presente estudio fue evaluar el efecto de la aplicación tópica de pomada de acetato de tocoferol en el alivio del dolor y la epitelización de la fisura anal crónica, comparándolo con el efecto de un tratamiento estándar con pomada de trinitrato de glicerilo.DISEÑO:Ensayo clínico con intención de tratar controlado, aleatorizado, de un solo centro, con dos grupos paralelos.ESCENARIOClínica Garcilaso adscrita a la Universidad Alfonso X (Madrid, España).PACIENTESPacientes con fisura anal crónica.INTERVENCIONESLos pacientes fueron aleatorizados en 2 grupos: pacientes que recibieron pomada de acetato de tocoferol y pacientes que recibieron pomada de trinitrato de glicerilo.PRINCIPALES MEDIDAS DE RESULTADOEl criterio de valoración principal fue la cuantificación del dolor anal 8 semanas después de comenzar el tratamiento, medido por la escala analógica visual que varía de 0 a 100 mm. Los criterios de valoración secundarios fueron la tasa de curación (durante el período de tratamiento de 8 semanas) y la tasa de recurrencia.RESULTADOSSe trataron ciento sesenta pacientes consecutivos, 80 en cada grupo. A las ocho semanas después del tratamiento, la puntuación media de dolor anal se redujo en 56.2 mm en el grupo de pomada de trinitrato de glicerilo en comparación con una disminución de la puntuación de dolor anal medio de 67.1 mm en el grupo de pomada de acetato de tocoferol (diferencia media: 10.9 mm (intervalo de confianza del 95%; 4.3 a 18.6; p = 0.018) Dieciséis semanas después de finalizar la terapia, la tasa de recurrencia fue del 13.2% en el grupo de pomada de trinitrato de glicerilo frente a 2.9 en el grupo de pomada de acetato de tocoferol (p = 0.031).LIMITACIONESAusencia de medidas manométricas del esfínter anal interno antes y después de los tratamientos. Ungüento de trinitrato de glicerilo como comparador activo, mientras que los bloqueadores de los canales de calcio son en realidad el tratamiento estándar de oro.CONCLUSIONESEl dolor anal fue significativamente menor en el grupo de ungüento de acetato de tocoferol que en el grupo de ungüento de trinitrato de glicerilo a las 8 semanas después del tratamiento. La pomada de acetato de tocoferol logró una mayor tasa de curación y una menor tasa de recurrencia 16 semanas después de finalizar el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B751. (Traducción-Dr. Jorge Silva Velazco).
-
2.
The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.
Mokhtari, M, Razzaghi, R, Momen-Heravi, M
Phytotherapy research : PTR. 2021;(4):2099-2107
Abstract
This study was conducted to determine the effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients with grade 3 DFU. Participants were randomly allocated into two groups (30 participants each group), received either 80 mg nanocurcumin daily for 12 weeks or placebo. Primary endpoints in this study were serum insulin levels and insulin resistance. Curcumin intake significantly decreased fasting plasma glucose (p = .02), insulin (p = .01), insulin resistance (p = .02), and significantly increased insulin sensitivity (p = .008) compared with the placebo. Moreover, curcumin intake led to a significant reduction in total- (p < .001), LDL-cholesterol (p < .001), and a significant increase in total antioxidant capacity (TAC) (p < .001) and total glutathione (GSH) (p = .01) compared with the placebo. However, there was no significant improvement in wound healing parameters. Overall, our study demonstrated that nanocurcumin intake in patients with DFU resulted in a significant improvement of glycemic control, total- and LDL-cholesterol, TAC, and GSH but did not affect the indicators of ulcer size.
-
3.
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.
-
4.
Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial.
Sim, IW, Borromeo, GL, Tsao, C, Hardiman, R, Hofman, MS, Papatziamos Hjelle, C, Siddique, M, Cook, GJR, Seymour, JF, Ebeling, PR
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;(26):2971-2980
Abstract
PURPOSE Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.
-
5.
Multinutrient Supplementation Increases Collagen Synthesis during Early Wound Repair in a Randomized Controlled Trial in Patients with Inguinal Hernia.
Kjaer, M, Frederiksen, AKS, Nissen, NI, Willumsen, N, van Hall, G, Jorgensen, LN, Andersen, JR, Ågren, MS
The Journal of nutrition. 2020;(4):792-799
-
-
Free full text
-
Abstract
BACKGROUND Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis. OBJECTIVE We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in inguinal hernia disease patients when undergoing hernia repair. METHODS In this exploratory randomized controlled trial, 21 men (age: 55.2 ± 2.8 y; BMI: 25.0 ± 0.7 kg/m2) scheduled for Lichtenstein inguinal hernia repair were assigned to multinutrient supplementation (n = 10; multinutrient group) or no multinutrient supplementation (n = 11; control group). The multinutrient group received 14 g l-arginine, 14 g l-glutamine, 1250 mg vitamin C, and 55 mg zinc daily starting 14 d before surgery and ending 14 d after surgery. The multinutrient and control groups received high-quality protein to ensure a daily intake of 1.5 g protein/kg. Collagen biosynthesis was measured by the biomarkers type I procollagen propeptide (CICP), type III procollagen propeptide (PRO-C3), and type V procollagen propeptide (PRO-C5) in the sera on days -14, 0, and 1, and in the wound fluids on postoperative days 1 and 2. Compliance was recorded after the 28-d intervention period. RESULTS Serum PRO-C5 concentrations decreased (P < 0.05) postoperatively in the control but not the multinutrient group. Neither CICP nor PRO-C3 serum concentrations differed significantly between the 2 groups. In wound fluid, the CICP concentrations increased (P < 0.05) from days 1 to 2 in the multinutrient group and were 49% higher (P = 0.10) than those in the control group on day 2. Wound fluid concentrations PRO-C3 and PRO-C5 showed no significant time or group differences. The 28-d compliance was similar (P = 0.27) in the 2 groups. CONCLUSION Oral supplementation with arginine, glutamine, vitamin C, and zinc augment collagen synthesis during the first 2 d after inguinal hernia repair. This trial was registered at clinicaltrials.gov as NCT03221686.
-
6.
Effects of sea salt rinses on subjects undergone to oral surgery: a single blinded randomized controlled trial.
Cantore, S, Ballini, A, Saini, R, Altini, V, De Vito, D, Pettini, F, Dipalma, G, Inchingolo, F
La Clinica terapeutica. 2020;(1):e46-e52
Abstract
PURPOSE It has been customary to explain the dentally beneficial effects of xylitol and certain other natural compound as lysozyme and seas salt in terms of microbiological effects only. Several studies have tested the use of natural ingredients, alcohol and fluoride free, in mouthwashes. The purpose of this study was to evaluate a combined mouthwash formulation containing natural antibiofilm agents in oral care wound healing after routinely oral surgery (extraction) procedures. METHODS Patients were assigned following a blinded randomized controlled trial and divided into two groups, an experimental group (I = 15) and a control (placebo) group (II = 15). Any infectious complications, wound healing, plaque accumulation in the stitches, and presence of trismus and inflammation were evaluated at ten and thirty days after extraction procedure. Pain and swelling were evaluated using the well-known visual analogue scale (VAS) scale throughout study period following extraction. The mean difference in Pre and Post values were compared among the groups. The change in pre-post score was analyzed using the paired t test. RESULTS An appreciable wound healing was seen in the experimental group when compared to the control sites, with no reported adverse effects. Four weeks postoperative patient's satisfaction level, to subjective and objective outcome measurements in documenting the result of a mouthwash treatment showed an interesting difference between groups. CONCLUSIONS Since combined mouthwash formulations, containing natural/bioactive substances, could provide a cheap, safe and acceptable alternative in oral care, further studies will also be required to study these effects and their mechanism of action in detail.
-
7.
A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFβ to stimulate remodeling of fibrotic venous leg ulcers.
Stone, RC, Stojadinovic, O, Sawaya, AP, Glinos, GD, Lindley, LE, Pastar, I, Badiavas, E, Tomic-Canic, M
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2020;(2):164-176
-
-
Free full text
-
Abstract
Venous leg ulcers (VLU) represent a major clinical unmet need, impairing quality of life for millions worldwide. The bioengineered bilayered living cell construct (BLCC) is the only FDA-approved therapy demonstrating efficacy in healing chronic VLU, yet its in vivo mechanisms of action are not well understood. Previously, we reported a BLCC-mediated acute wounding response at the ulcer edge; in this study we elucidated the BLCC-specific effects on the epidermis-free ulcer bed. We conducted a randomized controlled clinical trial (ClinicalTrials.gov NCT01327937) enrolling 30 subjects with nonhealing VLUs, and performed genotyping, genomic profiling, and functional analysis on wound bed biopsies obtained at baseline and 1 week after treatment with BLCC plus compression or compression therapy (control). The VLU bed transcriptome featured processes of chronic inflammation and was strikingly enriched for fibrotic/fibrogenic pathways and gene networks. BLCC application decreased expression of profibrotic TGFß1 gene targets and increased levels of TGFß inhibitor decorin. Surprisingly, BLCC upregulated metallothioneins and fibroblast-derived MMP8 collagenase, and promoted endogenous release of MMP-activating zinc to stimulate antifibrotic remodeling, a novel mechanism of cutaneous wound healing. By activating a remodeling program in the quiescent VLU bed, BLCC application shifts nonhealing to healing phenotype. As VLU bed fibrosis correlates with poor clinical healing, findings from this study identify the chronic VLU as a fibrotic skin disease and are first to support the development and application of antifibrotic therapies as a successful treatment approach.
-
8.
Evaluation of the effect of honey on the healing of tooth extraction wounds in 4- to 9-year-old children.
Mokhtari, S, Sanati, I, Abdolahy, S, Hosseini, Z
Nigerian journal of clinical practice. 2019;(10):1328-1334
Abstract
OBJECTIVE The aim of the this study was to evaluate the effect of honey on the healing of tooth extraction wounds in children 4‒9 years of age. SUBJECTS AND METHODS In the present randomized clinical trial, 51 patients, 4‒9 years of age were selected randomly. All the subjects required extraction of one deciduous molar tooth. The subjects were randomly assigned to two groups. In group 1, after extraction of the tooth, the dentist used a cotton swab applicator to place a layer of honey on a piece of gauze moistened with normal saline solution (NSS) and placed it on the socket. In group 2, honey was not used; rather, NSS was applied. On days 3 and 7 after tooth extraction, the wound sizes were measured. RESULTS In both groups, the wound sizes decreased significantly on the third day compared with baseline and on the seventh day compared with the third day (P < 0.05). On the third and seventh days after tooth extraction, wound sizes in the honey group were significantly lower than those in the NSS group (P < 0.05). CONCLUSION Honey resulted in a decrease in wound sizes and faster healing after extraction of teeth in children. Therefore, use of honey can be recommended after minor surgeries in the oral cavity.
-
9.
A prospective randomized trial of a potassium competitive acid blocker vs proton pump inhibitors on the effect of ulcer healing after endoscopic submucosal dissection of gastric neoplasia.
Komori, H, Ueyama, H, Nagahara, A, Akazawa, Y, Takeda, T, Matsumoto, K, Matsumoto, K, Asaoka, D, Hojo, M, Yao, T, et al
The Journal of international medical research. 2019;(4):1441-1452
Abstract
BACKGROUND/AIMS: Vonoprazan is a new a potassium-competitive acid blocker (P-CAB) that was recently developed in Japan. However, vonoprazan's efficacy in healing gastric ulcers after endoscopic submucosal dissection (ESD) remains controversial. This study aimed to compare the efficacy of P-CABs and proton pump inhibitors (PPIs) in healing post-ESD ulcers. MATERIALS AND METHODS This prospective randomized controlled trial (UMIN000017386) enrolled 40 patients with gastric neoplasia, who underwent ESD at our hospital from April 2015 to January 2016. Before ESD, patients were randomly divided into the following two groups: group V, vonoprazan 20 mg/day; or group R, rabeprazole 10 mg/day. Medications were taken 1 day before to 4 weeks after ESD. The ESD-induced artificial ulcer size was measured just after ESD and 4 weeks after ESD to calculate the reduction rate as follows: (ulcer area 4 weeks after ESD)/(ulcer area just after ESD) × 100. RESULTS Eighteen patients in group V and 15 patients in group R were analyzed. The mean reduction rate was significantly different in groups V and R (93.3% vs 96.6%, respectively). Post-ESD bleeding was observed in two patients in group R and drug-induced hepatic injury in one patient in group R. CONCLUSION Rabeprazole facilitated the healing process post-ESD.
-
10.
The effect of alpha lipoic acid on uterine wound healing after primary cesarean section: a triple-blind placebo-controlled parallel-group randomized clinical trial.
Sammour, H, Elkholy, A, Rasheedy, R, Fadel, E
Archives of gynecology and obstetrics. 2019;(3):665-673
Abstract
PURPOSE To investigate the effect of alpha lipoic acid (ALA) on uterine wound healing after primary cesarean section (CS). METHODS A parallel-group, triple-blind, placebo-controlled randomized clinical trial was conducted in Ain Shams University Maternity Hospital, Cairo, Egypt, involving 102 women undergoing pre-labor primary CS. The participants were randomly assigned using a computer-generated list of random numbers to receive oral ALA or a placebo twice daily for 6 weeks after CS. Allocation to either group was in a 1:1 ratio by an independent statistician (not involved in the treatment or data collection). The primary outcome was the presence of CS defect and measuring its depth and width. Secondary outcomes were measurements of the anterior myometrial and residual myometrium thicknesses, healing ratio and the presence of intrauterine adhesions. Assessment was done using saline contrast sonohysterography. RESULTS Twenty (39.2%) women in the treatment group and ten (19.6%) controls had no niche (P value = 0.03, 95% CI - 0.388, - 0.0037). The absolute and relative risk reduction of forming a niche was 19.61% and 24.39%, respectively. The number of women needed to treat was five to avoid one niche formation. ALA use was associated with gastrointestinal upset in only three participants; however, none of the women withdrew during the study. CONCLUSION In women undergoing primary CS, the administration of ALA for 6 weeks postpartum improved uterine healing and decreased the incidence of scar niche.