Combined strategies following surgical drainage for perianal fistulizing Crohn's disease: failure rates and prognostic factors.

AIM: The medico-surgical strategy for the treatment of perianal fistulizing Crohn's disease (CD) following surgical drainage remains challenging and debated. Our aims were to describe the failure rate of therapeutic interventions after drainage of the fistula tract and determine the factors associated with failure to optimize medico-surgical strategies. METHOD: All consecutive patients with perianal fistulizing CD who underwent surgical drainage with at least a 12-week follow-up were included. Failure was defined as the occurrence of at least one of the following items: abscess recurrence, purulent discharge from the tract, visible external opening and further drainage procedure(s). RESULTS: One hundred and sixty-nine patients were included. The median follow-up was 4.0 years. The cumulative failure rates were 20%, 30% and 36% at 1, 3 and 5 years, respectively. The cumulative failure rates in patients who had sphincter-sparing surgeries or seton removal were significantly higher than in those who had a fistulotomy. Anterior fistula [hazard ratio (HR) = 2.52 (1.13-5.61), P = 0.024], supralevator extension [HR = 20.78 (3.38-127.80), P = 0.001] and the absence or discontinuation of immunosuppressants after anal drainage [HR = 3.74 (1.11-12.5), P = 0.032] were significantly associated with failure in the multivariate analysis model. CONCLUSION: Combined strategies for perianal fistulizing CD lead to a failure rate of 36% at 5 years. Where advisable, fistulotomy may be preferred because it has a lower rate of recurrence. The benefits of immunosuppressants require a dedicated prospective randomized trial.

Sphincter-sparing surgery for complex anal fistulas: radiofrequency thermocoagulation of the tract is of no help.

AIM: To compare the rate of failure of radiofrequency thermocoagulation for anal fistula with that of rectal advancement flap in a case-matched study. METHOD: Patients who underwent radiofrequency treatment were compared with age- and sex-matched patients with Crohn's disease (CD) who underwent a rectal flap procedure. Fistula features, general characteristics and the main clinical events were recorded in a prospective database. Failure was defined by at least one of following: abscess, purulent discharge, visible external opening or further drainage procedure. RESULTS: A total of 62 patients [median age 45 (range 36.8-57.5) years; 22 women, 40 men; 22 with CD] were analysed. The failure rate of radiofrequency treatment was higher than that of rectal flap treatment (74.2% vs 32.2%; P = 0.004). The cumulative probabilities of failure of the radiofrequency treatment were 53.8% (38.8-68.3), 71.8% (55.3-84.0) and 87.4% (70.6-95.3) at 3, 6 and 12 months, respectively. Three patients in the radiofrequency group required drainage for an abscess and one had severe thermal ulceration. The Cox proportional hazards regression model (surgical procedure, obesity, CD) showed rectal flap treatment [3.48 (1.60-8.07); P = 0.001] and CD [2.60 (1.16-6.41); P = 0.02] to be the main independent predictors of healing. CONCLUSION: Radiofrequency thermocoagulation is a less satisfactory sphincter-sparing treatment for the management of anal fistula than a rectal flap procedure.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

AIM: Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. RESULTS: Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24 months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P = 0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. CONCLUSION: Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

TGF-ß1 differentially modulates the collagen VI α5 and α6 chains in human tendon cultures.

Collagen VI is a microfibrillar collagen with a potential regulatory role in tendon repair mechanism. We studied the expression of collagen VI α5 and α6 chains in normal human tendon fibroblast cultures, both under basal condition and in response to TGF-ß1, a potent regulator of tendon healing. Under basal condition, we found that the α5 chain was expressed, although to a lesser extent with respect to the α3 chain; in contrast, the α6 chain was absent. The treatment with TGFß1 induced an opposite effect on the expression of the α5 and α6 chains; in fact, while the α5 chain was dramatically reduced, the α6 chain was induced and released in the culture medium. These data indicate that collagen VI α5 and α6 chains are differentially involved in tendon matrix homeostasis. The α6 chain may represent a new potential biomarker for monitoring TGFß1-related events in tendon, as healing and fibrotic scar formation.

Defective collagen VI α6 chain expression in the skeletal muscle of patients with collagen VI-related myopathies.

Collagen VI is a non-fibrillar collagen present in the extracellular matrix (ECM) as a complex polymer; the mainly expressed form is composed of α1, α2 and α3 chains; mutations in genes encoding these chains cause myopathies known as Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM). The collagen VI α6 chain is a recently identified component of the ECM of the human skeletal muscle. Here we report that the α6 chain was dramatically reduced in skeletal muscle and muscle cell cultures of genetically characterized UCMD, BM and MM patients, independently of the clinical phenotype, the gene involved and the effect of the mutation on the expression of the "classical" α1α2α3 heterotrimer. By contrast, the collagen VI α6 chain was normally expressed or increased in the muscle of patients affected by other forms of muscular dystrophy, the overexpression matching with areas of increased fibrosis. In vitro treatment with TGF-ß1, a potent collagen inducer, promoted the collagen VI α6 chain deposition in the ECM of normal muscle cells, whereas, in cultures derived from collagen VI-related myopathy patients, the collagen VI α6 chain failed to develop a network outside the cells and accumulated in the endoplasmic reticulum. The defect of the α6 chain points to a contribution to the pathogenesis of collagen VI-related disorders.

Arthroscopic Lunate Excision for Stage 3 Kienbock's Disease.

Background The ideal treatment of stage 3 Kienbock's disease is uncertain, with current open procedures conferring the risk of carpal instability, ulnar translocation, and stiffness. We present our technique of arthroscopic lunate excision, and discuss our short- to medium-term results. Description of Technique Via standard wrist arthroscopic portals, the lunate is excised using a combination of shavers, burrs, and rongeurs. Care is taken to preserve the extreme dorsal and volar cortices of the lunate to prevent carpal instability. A short arm backslab is applied for 2 weeks, after which the patient commences range of motion. Patients and Methods Consecutive patients undergoing arthroscopic lunate excision at a single center in Paris, France, underwent pre- and postoperative assessment. Parameters assessed include range of motion, as well as patient-reported outcome measures (PROMs). Results A cohort of 13 patients (7 females and 6 males with a mean age of 27.2 years) underwent arthroscopic lunate excision, and were followed up for a mean of 1.96 years. Significant improvements were noted in flexion, extension, pronation, grip strength, and PROMs. Conclusions Arthroscopic lunectomy provides significant improvements in clinical and PROMs at short- to medium-term follow-up, and conserves other salvage options in case of failure. Long-term clinical follow-up and further biomechanical studies would be beneficial.

Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome.

One form of congenital muscular dystrophy, rigid spine syndrome (MIM 602771), is a rare neuromuscular disorder characterized by early rigidity of the spine and respiratory insufficiency. A locus on 1p35-36 (RSMD1) was recently found to segregate with rigid spine muscular dystrophy 1 (ref. 1). Here we refine the locus and find evidence of linkage disequilibrium associated with SEPN1, which encodes the recently described selenoprotein N (ref. 2). Our identification and analysis of mutations in SEPN1 is the first description of a selenoprotein implicated in a human disease.

Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.

Critical evaluation of the use of cell cultures for inclusion in clinical trials of patients affected by collagen VI myopathies.

Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1(-/-) mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established.

Joint-sparing arthroscopic management of avascular necrosis of the capitate.

Avascular necrosis of the proximal pole of the capitate is an exceedingly rare pathology with few therapeutic solutions. The largest published series concerned a cohort of 6 cases over 10 years. The present case concerns our experience with avascular necrosis of the capitate in a 20-year-old woman. Due to her age and high functional demand, we opted for a minimally invasive solution using arthroscopy. We performed an X-shaped palmaris longus tendon interposition arthroplasty at the midcarpal joint between the capitate and the lunate. We here report 2 years' follow-up.

Applying the WALANT technique to surgical treatment of distal radius fractures.

The Wide-Awake Local Anesthesia No Tourniquet (WALANT) method is a recent anesthesia option for surgery of the upper limbs based on the injection of an anesthetic solution containing adrenaline at the surgical site, hence circumventing tourniquet use. In a prospective study, we compared the functional outcomes using this anesthesia technique with those of the regional anesthesia (RA) technique for the surgical care of distal radius fractures (DRF). From November 2019 to June 2020, a non-randomized, single-center study was conducted with a cohort of 41 patients suffering from a DRF and who received volar plate fixation at a university hospital center. Twenty-one patients had WALANT surgery and 20 had RA with installation of a tourniquet. Over a period of 7 months, the clinical and radiological outcomes as well as the QuickDASH functional score were evaluated. Recovery of wrist function return to work, and analgesic withdrawal for the WALANT group occurred earlier than for the RA group. No noticeable differences were found regarding surgery duration or radiographic results. Using WALANT, functional wrist recovery occurs earlier than with RA. In our study, earlier analgesic stoppage, a quicker return to work and resumption of activity were observed with WALANT. As such, it should become part of the therapeutic arsenal for surgical treatment of DRF.

Solitary rectal ulcer syndrome in 102 patients: Do different phenotypes make sense?

BACKGROUND: Little is known about the pathophysiological mechanisms of solitary rectal ulcer syndrome (SRUS). AIMS: We aim to identify the different phenotypes, taking into account complaints, anatomy and anorectal physiology. METHODS: Complaints, endoscopy results, and physiology data of patients with histologically proven SRUS were collected and analysed. The associated anorectal diseases were faecal incontinence and obstructed defecation. The clinical aspects of SRUS were compared, and factors associated with anorectal diseases were identified. RESULTS: Overall, 102 consecutive patients were included. The predominant lesion was a rectal ulcer (66%), and inflammation of the rectal wall was present in 42% of patients. Abnormal rectal capacities and/or rectal perception was observed in more than half. Nearly half (52%) of the patients met the criteria for obstructed defecation and they tended to more frequently have psychiatric disease (66.7% vs 33.3%; p=0.07). Patients with faecal incontinence (17%) reported more self-perception of anal procidentia (p=0.01) and were more likely to have inflammation of the rectal wall (p=0.02), high-grade internal rectal procidentia (p=0.06) and anal hypotonia (p=0.004); their maximum tolerable volume was lower (p=0.004). CONCLUSION: The characteristics of patients with SRUS suggest different phenotypes. This may be a way to develop a comprehensive treatment strategy.

Dystrophin restoration in skeletal, heart and skin arrector pili smooth muscle of mdx mice by ZM2 NP-AON complexes.

Potentially viable therapeutic approaches for Duchenne muscular dystrophy (DMD) are now within reach. Indeed, clinical trials are currently under way. Two crucial aspects still need to be addressed: maximizing therapeutic efficacy and identifying appropriate and sensible outcome measures. Nevertheless, the end point of these trials remains painful muscle biopsy to show and quantify protein restoration in treated boys. In this study we show that PMMA/N-isopropil-acrylamide+ (NIPAM) nanoparticles (ZM2) bind and convey antisense oligoribonucleotides (AONs) very efficiently. Systemic injection of the ZM2-AON complex restored dystrophin protein synthesis in both skeletal and cardiac muscles of mdx mice, allowing protein localization in up to 40% of muscle fibers. The mdx exon 23 skipping level was up to 20%, as measured by the RealTime assay, and dystrophin restoration was confirmed by both reverse transcription-PCR and western blotting. Furthermore, we verified that dystrophin restoration also occurs in the smooth muscle cells of the dorsal skin arrector pili, an easily accessible histological structure, in ZM2-AON-treated mdx mice, with respect to untreated animals. This finding reveals arrector pili smooth muscle to be an appealing biomarker candidate and a novel low-invasive treatment end point. Furthermore, this marker would also be suitable for subsequent monitoring of the therapeutic effects in DMD patients. In addition, we demonstrate herein the expression of other sarcolemma proteins such as alpha-, beta-, gamma- and delta-sarcoglycans in the human skin arrector pili smooth muscle, thereby showing the potential of this muscle as a biomarker for other muscular dystrophies currently or soon to be the object of clinical trials.

Incidental anal 18fluorodeoxyglucose uptake: Should we further examine the patient?

BACKGROUND: There are no studies on incidental anal 18F-fluorodeoxyglucose (18FDG) uptake. AIM: To assess the rate and aetiologies of incidental anal 18FDG uptake and to evaluate the correlation between 18FDG positron-emission tomography/computed tomography (PET/CT) parameters and the diagnosis of an anorectal disease. METHODS: The data from patients with incidental anal 18FDG uptake were retrospectively analysed. Patients who underwent anorectal examinations were identified and compared to those who did not undergo examinations. Patients who were offered treatment were then identified and compared to those who did not receive treatment. RESULTS: Among the 43020 18FDG PET/CT scans performed, 197 18FDG PET/CT scans of 146 patients (0.45%) reported incidental anal uptake. Among the 134 patients included, 48 (35.8%) patients underwent anorectal examinations, and anorectal diseases were diagnosed in 33 (69.0%) of these patients and treated in 18/48 (37.5%) patients. Among the examined patients, those with a pathology requiring treatment had significantly smaller metabolic volumes (MV) 30 and MV41 values and higher maximal and mean standardized uptake value measurements than those who did not require treatment. CONCLUSION: Incidental anal 18FDG uptake is rare, but a reliable anorectal diagnosis is commonly obtained when an anorectal examination is performed. The diagnosis of an anorectal disease induces treatment in more than one-third of the patients. These data should encourage practitioners to explore incidental anal 18FDG uptake systematically.

Transcriptional behavior of DMD gene duplications in DMD/BMD males.

DMD gene exons duplications account for up to 5-10 % of Duchenne (DMD) and up to 5-19% of Becker (BMD) muscular dystrophies; as for the more common deletions, the genotype-phenotype correlation and the genetic prognosis are generally based on the "reading frame rule". Nevertheless, the transcriptional profile of duplications, abridging the genomic configuration to the eventual protein effect, has been poorly studied. We describe 26 DMD gene duplications occurring in 33 unrelated patients and detected among a cohort of 194 mutation-positive DMD/BMD patients. We have characterized at the RNA level 16 of them. Four duplications (15%) behave as exception to the reading frame rule. In three BMD cases with out-of-frame mutations, the RNA analysis revealed that exon skipping events occurring in the duplicated region represent the mechanism leading to the frame re-establishment and to the milder phenotype. Differently, in a DMD patient carrying an in-frame duplication the RNA behaviour failed to explain the clinical phenotype which is probably related to post-transcriptional-translational mechanisms. We conclude that defining the RNA profile in DMD gene duplications is mandatory both for establishing the genetic prognosis and for approaching therapeutic trials based on hnRNA modulation.

Poor outcomes of fusion with Trabecular Metal implants after failed total ankle replacement: Early results in 11 patients.

INTRODUCTION: One of the reasons for revision of total ankle replacement (TAR) implants is loosening due to subchondral cysts. Reconstruction and fusion of the ankle is often the first choice for revision procedures due to the large bone defects, which are typically filled with autograft and/or allograft. Filling the defect with a trabecular metal tantalum implant is a potential alternative given the biomechanical properties of this component. HYPOTHESIS: Using tantalum as a spacer provides primary stability and contributes to fusion of the ankle joint after removal of failed TAR implants. METHODS: Eleven patients underwent arthrodesis an average of 6.9 years after TAR. The mean height of the bone defect was 32mm. It was filled with a specially designed quadrangular implant (Trabecular Metal™, Zimmer/Biomet) combined with an iliac crest graft. Ten patients underwent tibio-talo-calcaneal (TTC) arthrodesis fixed with an angled retrograde nail and one patient underwent talocrural arthrodesis fixed with two plates (anterolateral and anteromedial). The clinical, functional (AOFAS and SF36 scores) and radiological (plain X-rays and CT scan) outcomes were determined. RESULTS: At a mean follow-up of 19.3 months, the mean total AOFAS score was 56 (21-78) and the mean SF36 score was 60.5 (19-84). One patient was lost to follow-up and four patients still had pain. The tantalum implant was integrated in six patients. Five patients achieved fusion of the subtalar joint and 8 achieved fusion of the talocrural joint. Three patients required surgical revision. DISCUSSION: Our hypothesis was not confirmed. The clinical outcomes after more than 1 year of follow-up are disappointing, as was the large number of nonunion cases and the lack of tantalum integration. These technical failures can be explained by insufficient construct stability and/or insufficient implant porosity. LEVEL OF EVIDENCE: IV (retrospective cohort study).

GDAP1 mutations in Czech families with early-onset CMT.

Mutations in the ganglioside-induced differentiation associated protein-1 gene (GDAP1) cause autosomal recessive (AR) demyelinating or axonal Charcot-Marie-Tooth neuropathy (CMT). In order to establish the spectrum and frequency of GDAP1 mutations in Czech population, we sequenced GDAP1 in 74 Czech patients from 69 unrelated families with early-onset demyelinating or axonal CMT compatible with AR inheritance. We identified three isolated patients with GDAP1 mutations in both alleles. In one additional sporadic and one familial case, the second pathogenic mutation remained unknown. Overall, we detected two different mutations, a novel R191X nonsense and a L239F missense mutation. L239F previously described in a German-Italian family is a prevalent mutation in Czech population and we give evidence for its common ancestral origin. All Czech GDAP1 patients developed involvement of all four limbs evident by the end of second decade, except for one isolated patient showing very slow disease progression. All patients displayed axonal type of neuropathy.

Hemi-arthroplasty for distal radius fracture in the independent elderly.

INTRODUCTION: The authors report their experience with hemi-arthroplasty in irreparable fresh distal radius fracture in independent elderly patients as first-line treatment (12 fractures in 11 women; mean age, 74 years) or in second line after clinically disabling primary failure (4 fractures in 4 women; mean age, 78 years). RESULTS: In the 12 primary surgeries, at a mean 32 months' follow-up, there were no complications requiring implant ablation; mean pain score was 1/10, flexion-extension 62°, Lyon Wrist score 75%, and Patient-Related Wrist Evaluation (PRWE) 22 points. In 2 of the 4 secondary surgeries, at a mean 24 months' follow-up, there were no complications requiring implant ablation; mean pain score was 2.5/10, flexion-extension 62°, Lyon Wrist score 58%, and PRWE 50 points: i.e., slightly poorer results than in primary surgery. CONCLUSION: Salvage of complex fracture in independent elderly patients by hemi-arthroplasty, whether primary or secondary to failure, seems to be a considerable progress, to be confirmed in larger series.

Reasons for and functional results of repeated hip arthroscopy: A continuous prospective study of 17 revisions out of 295 primary hip arthroscopies at mean 28months' follow-up.

INTRODUCTION: The rate of iterative arthroscopy has been increasing over the last decade as the technique has grown. The results of and reasons for these revision procedures, however, are not exactly known. We therefore conducted a prospective study to shed light on: 1) functional results and patient satisfaction following repeated arthroscopy, and 2) the relevant indications. HYPOTHESIS: Functional scores and patient satisfaction increase following repeated arthroscopy. MATERIALS AND METHOD: A single-center continuous prospective study without control group included patients undergoing repeated hip arthroscopy between September 2010 and September 2014, with a mean 28months' follow-up (median, 23.3months; range, 12-62months). Preoperative and follow-up functional assessment used the modified Harris hip, WOMAC and Christensen (NHAS) questionnaires, and a satisfaction scale. On etiological analysis, repeated arthroscopy was indicated if a cause of recurrent or persistent pain accessible to arthroscopic treatment was identified. RESULTS: Seventeen patients were included out of 295 primary arthroscopies (5.7%): 9 male, 8 female; median age, 29.6years (range, 16-48years). Indications for primary arthroscopy comprised 13 cases of femoroacetabular impingement, 3 labrum lesions with instability, 1 chondromatosis and 1 case of osteoarthritis. Eleven of the 17 primary lesions showed persistence, including 9 of the 13 cases of femoroacetabular impingement. There were 3 failures in 17 repeated arthroscopies. All functional scores improved, with a gain of 7 points (P<0.06) on modified Harris hip score, 25 points (P<0.0006) on WOMAC score, and 27 points (P<0.001) on NHAS score. Ten of the 17 patients were satisfied or very satisfied with the repeated arthroscopy (59%). CONCLUSION: Although less good than on primary arthroscopy, functional results on repeated hip arthroscopy were satisfactory in the short term. The main reason for repeated arthroscopy was persistence of initial abnormality due to insufficient treatment.

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

BACKGROUND: The natural history of anal ulcerations in Crohn's disease remains unknown. AIMS: To assess the long-term outcomes of anorectal ulcerations. METHODS: Data from consecutive patients with perineal Crohn's disease were prospectively recorded. The data of patients with anal ulceration were extracted. RESULTS: Anal 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. CONCLUSION: Anal 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.