Sustained Healing Research Articles

Insider community-engaged research for Latinx healing in nature: Reflections on and extensions from Phase 1 of the Promoting Activity and Stress Reduction in the Outdoors (PASITO) project

In Spanish, pasito means “small step,” and in Phase 1 of the PASITO (Promoting Activity and Stress Reduction in the Outdoors) project we took small steps towards reclaiming nature for Latinx communities. The Latinx reclamation of green spaces for healing is a necessary step alleviating the observed unequal burden of chronic and infectious disease. Paradoxically, the Latinx community who could greatly benefit from green spaces has reduced access, as is the case for many poor communities of color. This perspective seeks to reflect on and utilize the lessons learned from PASITO in order to expand the positive impacts of nature for communities of color. Through self-reflection by members of the academic research team and a community leader, as well as preliminary analysis of qualitative data gathered from PASITO participants, we share insights from a community-engaged research project. Our approach validated culturally competent research practices with insider researchers, as well as culturally sensitive biospecimen collection, and revealed steps towards recruitment, retention, and healing for Latinx participants in research projects. These findings come at a pivotal time for park stewards and green space researchers as the need for spaces for healing accelerates for all communities of color, including Latinx, as we face a society plagued by biological and social reckonings. To find true and sustained healing within these communities calls for communities to progress from small steps towards giant strides in the reclamation of natural landscapes for well-being.

Burden of disease and adaptation to life in patients with Crohn\u2019s perianal fistula: a qualitative exploration

BackgroundPerianal fistulas are a challenging manifestation of Crohn’s disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning.MethodsThis exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn’s anal fistulas, from national IBD / bowel disease charities. The “standards for reporting qualitative research” (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers.ResultsTwelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate.ConclusionCrohn’s perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.

Fast and sustained healing of resistant corneal ulcers using corneal scrubbing and matrix regenerating therapy.

The aim of this study was to assess the efficacy and safety of corneal scrubbing associated with matrix regenerating agent on corneal wound healing in patients with persistent corneal ulcers. This was a retrospective case study in patients with difficult-to-treat corneal ulcer. Corneal scrubbing was performed with a sterile dry cotton bud to eliminate damaged epithelial cells and corneal deposits, promoting epithelial renewal. Regenerating agent was then administered as one eye drop every 2 days in addition to preservative-free ocular lubricants. A bandage contact lens was applied in case of moderate-to-severe corneal pain. Corneal ulcers were regularly assessed until healing. In total, 17 patients with a chronic corneal ulcer of various etiologies for several months on average were enrolled. Corneal scrubbing combined with regenerating agent administration led to a rapid corneal ulcer size reduction from 26.4 ± 20.6 mm2 after scrubbing (before regenerating agent) to 7.2 ± 7.1 mm2 at day 5, 3.3 ± 6.0 mm2 at day 10, and 0.9 ± 2.3 mm2 at day 18. Complete corneal ulcer healing was observed in 35.2% of patients within 10 days, in 70.4% within 18 days, and in all patients within 25 days. Corneal ulcer relapse was observed in two (11.8%) patients after 6 weeks and 5 months, respectively; both were successfully treated using the same procedure. The regenerating agent was well tolerated in all patients. In this study, combined corneal scrubbing and matrix regenerating therapy (with or without bandage contact lens) led to a rapid healing and successful resolution of persisting corneal ulcers, including large and deep corneal ulcers.

Stem cell therapy for perianal Crohn's.

Perianal Crohn's disease is a morbid and disabling condition, notoriously difficult to successfully treat with conventional medical and surgical therapies. Mesenchymal stem cells (MSCs) are an emerging novel therapy for perianal Crohn's disease. Over 300 patients with perianal Crohn's disease have now been treated with MSCs in the context of clinical trials. All trials have demonstrated safety, and efficacy superior to conventional therapy with biologics and surgical intervention. This was consistent despite the heterogeneity in study protocols including variability in cell dosing, mode of delivery, repeat dosing, and allogeneic versus autologous donors. Sustained healing to 1 year has also been demonstrated in a recent extension of the largest phase III study confirming superior efficacy of MSCs to placebo at 1-year follow-up. However, several outstanding questions regarding the use of MSCs for perianal Crohn's disease remain, which, if answered, could enhance MSCs' treatment efficacy. These include defining the optimal MSC donor, optimal MSC source (e.g., bone marrow versus adipose tissue), investigating a potential alloimmune response following allogeneic cellular delivery, and determining the optimal mode for MSC delivery. In addition to these unanswered questions, significant challenges in the required infrastructure and cost required for cell-based therapies may drive future research toward identifying novel acellular therapies. Novel regenerative therapies offer promising new treatment options for perianal Crohn's disease, without the risk of opportunistic infection seen with biologics and incontinence with surgical techniques. Future research will help define the optimal MSC product and treatment protocol, and may even expand our horizon of regenerative medicine into acellular therapy as well as cell-based therapies.

Cenegermin for Treating Neurotrophic Keratitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of cenegermin (OXERVATE®, Dompé) to submit evidence for the clinical and cost effectiveness of cenegermin for neurotrophic keratitis (NK). The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG’s review of the evidence submitted by the company and provides a summary of the Appraisal Committee’s (AC) final decision. Clinical-effectiveness evidence from two phase II randomised controlled trials (RCTs) of cenegermin found cenegermin to improve corneal healing after 8 weeks compared with vehicle, considered a proxy for artificial tears. Longer-term data and comparisons with other relevant comparators were insufficient to draw conclusions. The company developed a de novo economic model that found cenegermin to be dominant when compared with artificial tears, except in one of seven scenarios. However, the ERG considered that the model had a major structural flaw in that it failed to allow patients to enter a ‘sustained healing’ state from ‘standard of care (SoC) non-healing’ and ‘SoC deteriorating’ states, or to move into an ‘SoC deteriorating’ state from an ‘SoC non-healing’ state. Following the first AC meeting, the company submitted a revised model with a revised model structure that removed the ‘SoC deteriorating’ state and introduced an ‘SoC healed’ state to sit alongside the existing ‘sustained healing’ and ‘SoC non-healing’ states from the original model. However, the ERG continued to express concerns, which included (1) extrapolation of the treatment effect of cenegermin over a patient’s lifetime; (2) the assumption that patients had two specialist visits a month; (3) the assumption that artificial tears, autologous serum eye drops and contact lenses continued for a lifetime after healing; (4) the simplified modelling of costs and utilities; and (5) the underlying uncertainty in the utility values. The ERG therefore considered the company’s model could not produce a robust incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. The ERG did however present an alternative ICER by amending the use and cost of autologous serum eye drops, contact lenses and artificial tears in the ‘healed’ and ‘non-healed’ states. Applying these changes produced an ICER of £302,717 per QALY gained. Because of uncertainties with the clinical- and cost-effectiveness evidence, the AC concluded that cenegermin cannot be recommended within its marketing authorisation for NK.

Clinical efficacy of 60-mg dexlansoprazole and 40-mg esomeprazole after 24 weeks for the on-demand treatment of gastroesophageal reflux disease grades A and B: a prospective randomized trial.

Purpose: Research comparing the clinical efficacy of dexlansoprazole and esomeprazole has been limited. This study aims to compare the clinical efficacy of single doses of dexlansoprazole (modified-release 60 mg) and esomeprazole (40 mg) after 24-week follow-up in patients with mild erosive esophagitis.Methods: We enrolled 86 adult GERD subjects, randomized in a 1:1 ratio to two sequence groups defining the order in which they received single doses of dexlansoprazole (n=43) and esomeprazole (n=43) for 8 weeks as initial treatment. Patients displaying complete symptom resolution (CSR) by the end of initial treatment (8 weeks) were switched to on-demand therapy until the end of 24 weeks. Follow-up endoscopy was performed either at the end of 24 weeks or when severe reflux symptoms occurred. Five patients were lost to follow-up, leaving 81 patients (dexlansoprazole, n=41; esomeprazole, n=40) in the per-protocol analysis.Results: The GERDQ scores at 4-, 8-, 12-, 16-, 20-, and 24-week posttreatment were less than the baseline score. The CSR, rate of symptom relapse, days to symptom resolution, sustained healing rate of erosive esophagitis, treatment failure rate, and the number of tablets taken in 24 weeks were similar in both groups. The esomeprazole group had more days with reflux symptoms than the dexlansoprazole group (37.3±37.8 vs 53.9±54.2; P=0.008). In the dexlansoprazole group, patients exhibited persistent improvement in the GERDQ score during the on-demand period (week 8 vs week 24; P<0.001) but not in the esomeprazole group (week 8 vs week 24; P=0.846).Conclusions: This study suggests that the symptom relief effect for GERD after 24 weeks was similar for dexlansoprazole and esomeprazole. Dexlansoprazole exhibited fewer days with reflux symptoms in the 24-week study period, with better persistent improvement in the GERDQ score in the on-demand period.(ClinicalTrials. gov number: NCT03128736)

Homeopathy in the Context of a World in Crisis

AbstractHealing patients who have to live in a destructive environment demands of us as homeopaths to also participate in the healing of the whole system. Setting homeopathic work into a global context we can see that with our large experience of working with crises, we can well contribute to a solution of the global problems. For many reasons, homeopathy can serve as a model of a sustainable healing art. Seeing ourselves as part of a global community of workers for change will also help us to be perceived in a different way.

A systematic review of the efficacy and limitations of venous intervention in stasis ulceration.

Surgical techniques to address various components of chronic venous disease are rapidly evolving. Their efficacy and generally good results in treating superficial venous reflux (SVR) have been documented and compared in patients presenting with pain and swelling. A growing amount of literature is now available suggesting their efficacy in patients with venous leg ulcer (VLU). This review attempts to summarize the efficacy and limitations of commonly used venous interventions in the treatment of SVR and incompetent perforator veins (IPVs) in patients with VLU. A systematic review of the published literature was performed. Two different searches were conducted in MEDLINE, Embase, and EBSCOhost to identify studies that examined the efficacy of SVR ablation and IPV ablation on healing rate and recurrence rate of VLU. In the whole review, 1940 articles were screened. Of those, 45 were included in the SVR ablation review and 4 in the IPV ablation review. Data were too heterogeneous to perform an adequate meta-analysis. The quality of evidence assessed by the Grading of Recommendations Assessment, Development, and Evaluation for the two outcomes varied from very low to moderate. Ulcer healing rate and recurrence rate were between 70% and 100% and 0% and 49% in the SVR ablation review and between 59% and 93% and 4% and 33% in the IPV ablation review, respectively. To explain those variable results, limitations such as inadequate diagnostic techniques, saphenous size, concomitant calf pump dysfunction, and associated deep venous reflux are discussed. Currently available minimally invasive techniques correct most venous pathologic processes in chronic venous disease with a good sustainable healing rate. There are still specific diagnostic and efficacy limitations that mandate proper match of individual patients with the planned approach.

Does Methodology Matter? A Long-Term Comparative Analysis of Current Homeopathic Methodologies

Introduction: Different popular methodological approaches arrive at different remedies as the most appropriate for a given patient. What does that mean with respect to reproducibility of clinical outcomes? The aim was to identify prescribing methods that would more consistently arrive at long-lasting, sustained healing in chronic disease.

Healing by Design: A Sustainable Healing Indoor Environment for Healthcare Facilities

In the past two decades, healthcare administrators and medical professionals are becoming aware of the need to create 'Healing Environments' that support the needs of patients, family and staff. The key factor motivating this awareness has been the growing scientific evidence linking a range of aspects of the built environment to patients' clinical outcomes and staff's effectiveness. Based on Evidence-Based Design, it was necessary to examine the incorporation of these aspects in sustainable design and to discover those aspects that need to be more addressed to promote healing environments and health in all its complexity for all the users of healthcare facilities, that‘s why a comparison between the physical characteristics of the indoor environment and the environmental interventions of healing environments in three Sustainable Rating Systems for Healthcare have been implemented. As a result, a checklist for Environmental Interventions to promote Psychological Comfort is developed to create a Healing Psychologically Supportive Environment that supports users' wellbeing and helps patients cope with stress that accompanies illness which can cause a person's immune system to be suppressed and can dampen a person's emotional and spiritual resources impeding recovery and healing, and aiming to encourage the incorporation of these physical features into future building initiatives.

Anal ulcerations in Crohn’s disease: Natural history in the era of biological therapy

BackgroundThe natural history of anal ulcerations in Crohn’s disease remains unknown. AimsTo assess the long-term outcomes of anorectal ulcerations. MethodsData from consecutive patients with perineal Crohn’s disease were prospectively recorded. The data of patients with anal ulceration were extracted. ResultsAnal ulcerations were observed in 154 of 282 patients (54.6%), and 77 cases involved cavitating ulcerations. The cumulative healing rates were 47%, 70% and 82% at 1, 2 and 3 years, respectively. Patients with a primary fistula phenotype had a shorter median time to healing of their anal ulceration (28 [13–83] weeks) than those with a stricture (81 [28–135] weeks) or those with isolated ulceration (74 [31–181] weeks) (p=0.004). Among patients with ulcerations but no fistula at referral (n=67), only 4 (6%) developed de novo abscesses and/or fistula during follow-up. There was no benefit associated with introducing or optimising biologics, nor with combining immunosuppressants and biologics. ConclusionAnal ulceration in Crohn’s disease usually requires a long time to achieve sustained healing. Determining the impact of biologics on healing rates will require dedicated randomised trials although it does not show a significant healing benefit in the present study.

Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs

Aim: To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). Design: A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). Results: After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. Conclusion: The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

Carcinogenesis and diabetic wound healing: evidences of parallelism.

There is a close association of chronic tissue damage, inflammation and cancer. A chronic injury may contribute to sustained healing response leading to fibrosis, organ failure and carcinogenesis. Wounds created due to mechanical or patho-physiological insults, generally follow a sophisticated series of mutually coherent steps leading to the re-establishment of the affected tissue or organ. The process of wound healing resembles fundamental processes like embryogenesis and tissue regeneration. All the stages in the wound healing process are tightly regulated and any sort of imbalance may lead to either non healing chronic ulcers or excessively healed hypertrophic scars. Diabetic wounds are also very tough to heal and in many cases they do not heal, ultimately resulting in the amputation of that body part. The non-healing property of diabetic wounds may be due to combined effect of intrinsic and extrinsic factors. In this review, we aimed to explore the steps involved in diabetic wound healing and compare it with the process of carcinogenesis. This review demonstrates that both carcinogenesis and the diabetic wound healing follow a similar path of latent healing in an abnormal exaggerated manner.

Effectiveness of platelet-rich plasma in healing necrobiosis lipoidica diabeticorum ulcers.

Necrobiosis lipoidica diabeticorum (NLD) is a chronic condition, which is characterized by single or multiple lesions on the legs, and occurs in 0.3% of patients with diabetes. Recently, platelet-rich plasma (PRP) has been used in several clinical settings to promote sustained healing and better outcome. We propose the use of PRP for the treatment of NLD-associated recalcitrant wounds. In this study, 15 patients were treated with homologous PRP; all showed marked enhancement in wound healing without any adverse effects. After PRP application, advanced dressings were used until closure of the lesion was obtained, which was complete for all our patients. We therefore propose the use of PRP for recalcitrant wounds in patients with NLD.

Eight Weeks of Esomeprazole Therapy Reduces Symptom Relapse, Compared With 4 Weeks, in Patients With Los Angeles Grade A or B Erosive Esophagitis

There is disagreement over the ideal duration of initial proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease, and whether prolonged therapy increases healing of the esophagitis and prevents symptom relapse. We performed a multicenter, prospective, randomized, controlled study to compare the efficacies of 4 weeks vs 8 weeks of PPI therapy in reducing reflux symptoms and preventing symptom relapse in patients with Los Angeles grade A or B erosive esophagitis. Consecutive patients with symptomatic Los Angeles grade A or B erosive esophagitis were assigned randomly to groups given daily esomeprazole (40 mg) for 4 weeks (n = 207) or 8 weeks (n = 201) as their initial treatment. Patients with complete symptom resolution were switched to on-demand therapy until the end of week 20. All patients underwent follow-up endoscopy at the end of week 20. Symptom relapse was defined as 2 or more episodes of troublesome reflux symptoms per week or ingestion of PPI for more than 7 days within 4 weeks, owing to reflux symptoms. The 4-week and 8-week groups had comparable rates of complete symptom resolution (77.9% vs 82.1%). However, the cumulative 12-week incidence of symptom relapse was higher for the 4-week group than for the 8-week group (62.5% vs 47.8%; difference, 14.7%; 95% confidence interval, 3.7%-25.7%; P = .009). No significant difference was observed between groups in the proportions of patients with sustained healing at the end of week 20 (49.6% vs 40.9%; P = .160). Prolonging PPI therapy from 4 weeks to 8 weeks does not appear to increase the rate of complete symptom resolution in patients with mild erosive esophagitis. However, 8 weeks of PPI therapy reduces symptom relapse, compared with 4 weeks, in patients with Los Angeles grade A or B erosive esophagitis. ClinicalTrials.gov number: NCT01874535.

Recent Advances in Pharmacotherapy of Ulcerative Colitis

Ulcerative colitis is a form of chronic inflammatory bowel disease (IBD) that produces inflammation and ulcers along the inside of the colon, which can interfere with the normal function of the colon. The disease typically starts to manifest in patients as young adults. Ulcerative colitis is an intermittent disease with periods of exacerbated symptoms, or flares, and periods that are relatively symptom-free. According to the Cohn’s and Colitis Foundation of America, several millions people suffer from ulcerative colitis worldwide. Current therapeutic approaches for ulcerative colitis are partially successful despites advances in GIT research. A significant proportion of patients with ulcerative colitis undergo colectomy. Nearly 50% patients do not achieve sustained remission, leading to impairment of physical and mental health, social life, employment issues and sexual activity. Budesonide is an oral, extended release synthetic corticosteroid that is recently approved for UC. Enteric-coated budesonide formulations resist gastric-acid degradation, delivering active drug to the small intestine and proximal colon. Budesonide is specifically indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. Budesonide has a high first-pass metabolism with minimal systemic absorption. This review describes recent advances in the pharmacotherapy of ulcerative colitis and outlines why future studies targeting sustained suppression of inflammation could have an enormous impact on the natural course of the disease. Ulcerative colitis needs intense therapy and it should be maintained until sustained remission and mucosal healing has been reached.

P031 Probiotic bacteria enhance antigen sampling and processing by dendritic cells in pediatric IBD

all prescribedmedications. Demographic, dietary and clinical information, PCDAI, Harvey Bradshaw (HB) and Lewis score (LS) were collected at 0, 12 and 52 weeks. CE’s were evaluated by an experienced reader blinded to patient clinical information and timing. Results: Sixteen patients were screened; 10 enrolled; and 9 completed the initial 12 week trial; receiving 85% of estimated caloric needs prior to, and 101%, on the SCD. HB significantly decreased from 3.3 +2.0 to 0.6 +1.3 (p=0.007) as did PCDAI (21.1 +5.9 to 7.8 +7.1; p=0.011). LS declined significantly from 2153+732 to 960+433 (p=0.012). Seven patients continued the SCD to 52weekswith HB (0.1 +0.4) and PCDAI (5.4 +5.5) remaining improved (p=0.016 and 0.027 compared to baseline) withmean LS at 1046 +372 and 2 patients showing sustained mucosal healing. Conclusions: Clinical and mucosal improvements were seen in childrenwith CD using the SCD over 12 and 52weeks. Additionally, CE can monitor mucosal improvement in treatment trials for pediatric CD. Further studies are critically needed to understand the mechanisms underlying SCD’s effectiveness in children with CD.

P378 High restarting rate among patients with Crohn's disease after cessation of one-year treatment period with biologicals: Result of national RASH study

Background: Infliximab has been shown to be effective for moderate-to-severe ulcerative colitis (UC). We evaluated the long-term outcome after Infliximab treatment in patients with distal steroids-dependent refractory UC. Methods: From January 2007 to October 2011 109 consecutive patients (median age 32 years, range 15 65) with distal active refractory UC (mean Mayo score 6, range 4 9) were treated with Infliximab (induction with 5mg/kg at week 0, 2, 6 and maintenance at the same dose every 8 weeks) and prospectively followed. Primary end-point was colectomy free survival. Secondary end-points were sustained clinical response and mucosal healing. Results: Thirty-one patients (28.5%) underwent colectomy during a median follow-up of 40 months (range 6 56). Mean time to colectomy was 24 months (range 12 45) after first infliximab infusion. Indipendent predictors of colectomy were absence of short-term endoscopic response and steroidsdependency. Short-term clinical response (defined as a decrease in the partial Mayo score of at least 3 points at week 12) was obtained in 73 patients (67%) and short-term mucosal healing (endoscopic portion of Mayo score 1 or less) in 62 patients (57%). Sustained clinical response was observed in 78 patients (71.5%). No serious adverse events were observed during the follow-up. Conclusions: Our single-center experience shows that 67% of patients have a clinical improvement after 6 weeks-treatment and 71.5% have colectomy-free survival during follow up. Infliximab is an effective treatment in moderate to severe distal ulcerative colitis in patients refractory to standard treatments.

P377 Long-term outcome after infliximab treatment for distal refractory ulcerative colitis. A single tertiary center experience

Background: Infliximab has been shown to be effective for moderate-to-severe ulcerative colitis (UC). We evaluated the long-term outcome after Infliximab treatment in patients with distal steroids-dependent refractory UC. Methods: From January 2007 to October 2011 109 consecutive patients (median age 32 years, range 15 65) with distal active refractory UC (mean Mayo score 6, range 4 9) were treated with Infliximab (induction with 5mg/kg at week 0, 2, 6 and maintenance at the same dose every 8 weeks) and prospectively followed. Primary end-point was colectomy free survival. Secondary end-points were sustained clinical response and mucosal healing. Results: Thirty-one patients (28.5%) underwent colectomy during a median follow-up of 40 months (range 6 56). Mean time to colectomy was 24 months (range 12 45) after first infliximab infusion. Indipendent predictors of colectomy were absence of short-term endoscopic response and steroidsdependency. Short-term clinical response (defined as a decrease in the partial Mayo score of at least 3 points at week 12) was obtained in 73 patients (67%) and short-term mucosal healing (endoscopic portion of Mayo score 1 or less) in 62 patients (57%). Sustained clinical response was observed in 78 patients (71.5%). No serious adverse events were observed during the follow-up. Conclusions: Our single-center experience shows that 67% of patients have a clinical improvement after 6 weeks-treatment and 71.5% have colectomy-free survival during follow up. Infliximab is an effective treatment in moderate to severe distal ulcerative colitis in patients refractory to standard treatments.

The role of electrical signals in murine corneal wound re‐epithelialization

Ion flow from intact tissue into epithelial wound sites results in lateral electric currents that may represent a major driver of wound healing cell migration. Use of applied electric fields (EF) to promote wound healing is the basis of Medicare-approved electric stimulation therapy. This study investigated the roles for EFs in wound re-epithelialization, using the Pax6(+/-) mouse model of the human ocular surface abnormality aniridic keratopathy (in which wound healing and corneal epithelial cell migration are disrupted). Both wild-type (WT) and Pax6(+/-) corneal epithelial cells showed increased migration speeds in response to applied EFs in vitro. However, only Pax6(+/+) cells demonstrated consistent directional galvanotaxis towards the cathode, with activation of pSrc signaling, polarized to the leading edges of cells. In vivo, the epithelial wound site normally represents a cathode, but 43% of Pax6(+/-) corneas exhibited reversed endogenous wound-induced currents (the wound was an anode). These corneas healed at the same rate as WT. Surprisingly, epithelial migration did not correlate with direction or magnitude of endogenous currents for WT or mutant corneas. Furthermore, during healing in vivo, no polarization of pSrc was observed. We found little evidence that Src-dependent mechanisms of cell migration, observed in response to applied EFs in vitro, normally exist in vivo. It is concluded that endogenous EFs do not drive long-term directionality of sustained healing migration in this mouse corneal epithelial model. Ion flow from wounds may nevertheless represent an important component of wound signaling initiation.