Inflammatory bowel disease (IBD) can present as either Crohn's disease or ulcerative colitis. Both phenotypes are inflammatory conditions of the gastrointestinal tract. Despite scientific advances, the overall incidence and morbidity of IBD continues to increase worldwide. Fortunately, we continue to develop novel therapies, in hopes of providing safer, more effective treatment options. Such therapies include cell therapy, exosome therapy, hyperbaric oxygen therapy, and central nerve stimulation. The aim of this review is to briefly highlight each of these novel therapeutic interventions as they relate to the treatment of IBD.

Background/Objectives: Our study describes hyperbaric oxygen therapy (HBOT) as an additional therapy in the conservative treatment of Crohn's disease (CD) and its benefit in the early postoperative period to prevent surgical complications and improve gastrointestinal motility. Methods: This retrospective study evaluated HBOT in patients hospitalized at the Clinical Hospital Center Split for complications of CD between 2015 and 2020. Patients (N = 61) aged 19 to 67 with perianal fistulas, abscesses, fistulas, obstruction, stenosis, or bleeding were included, excluding those with ulcerative colitis or requiring intensive care. Patients were retrospectively divided into conservatively and surgically treated groups, and HBOT was administered over 15-25 days, with treatment lasting 60 min at 2.2 absolute atmospheres (ATA). We analyzed treatment outcomes between the HBOT-treated surgical and conservative groups and compared patients treated with HBOT to a cohort from the preceding five years who did not receive HBOT. Results: We treated 61 CD patients with HBOT, including 34 conservatively and 27 surgically treated patients. HBOT significantly reduced disease activity indices (311.7 ± 59.1 vs. 114 ± 29.8; 203.6 ± 24.1 vs. 83.8 ± 15, for conservatively treated patients, and 352.8 ± 45.7 vs. 109 ± 22.8; 270.4 ± 19.7 vs. 140.3 ± 10.6 for surgically treated patients) and accelerated bowel peristalsis recovery, with 94.1% of conservatively treated patients achieving remission. Comparison with a historical cohort showed faster recovery and improved outcomes in the HBOT group. Conclusions: HBOT is useful in postponing or avoiding surgical treatment, and in operated patients, it improves postoperative recovery and reduces the rate of postoperative complications.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly enlarging, painful ulcers with undermined borders. The management of PG is challenging due to the lack of standardized evidence-based treatments.

This review examines recent efforts to establish standardized outcomes for clinical trials to facilitate the drug development process for PG. It explores new therapeutics in development and evaluates advanced options for wound and pain management. Literature available on the pathogenesis, treatment, and pain management of PG from database inception to April 2024 was searched in PubMed, Embase, and Cochrane. ClinicalTrials.gov and the EU Clinical Trials Register were searched for clinical trials on PG.

New therapeutics such as interleukin 36 inhibitor and complement component C5a inhibitor more specifically target key pathways in the pathogenesis of PG have shown promise and can greatly benefit patients with PG, which still lacks an FDA-approved treatment. In addition to systemic therapy, local wound care and pain management should be carried out simultaneously to achieve successful wound healing.

This article discusses the literature review article by Pacheco et al published in July 2024; the authors provided good reviews of perianal Crohn's disease (CD), and challenges faced by clinicians in the management. CD, characterized by its chronic and relapsing nature, is an idiopathic condition that can involve any segment of the gastrointestinal tract. Perianal disease impacts up to 40% of patients with CD, with perianal fistulas constituting up to 80% of perianal lesions. Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients. The management focuses on controlling the perianal sepsis and treating luminal CD. Biologics are crucial to the treatment approach, and results have been encouraging. The surgery focuses on controlling the sepsis, with more definitive treatments being fistula surgery, fecal diversion, and proctectomy as the last resort. This manuscript briefly describes the burden of CD, the challenges posed by perianal CD, and the role of different treatment modalities from colorectal surgeon's perspective.

Crohn's disease is a chronic, complex inflammatory disorder of the gastrointestinal tract. Among its most challenging complications are perianal fistulas.

This study aims to explore the efficacy of hyperbaric oxygen therapy (HBOT) in reducing the activity of perianal fistulas in Crohn's disease patients.

This study enrolled patients diagnosed with Crohn's disease-associated perianal fistulas, with a disease duration of at least 3 years. Participants underwent HBOT in conjunction with standard medical therapy. The therapeutic effects were assessed at predetermined intervals using the Crohn's Disease Activity Index (CDAI), and laboratory parameters including faecal calprotectin levels, C-reactive protein (CRP) activity, serum iron concentration, and peripheral blood haemoglobin levels. Additionally, the Simple Endoscopic Score for Crohn's Disease (SESCD) and the Perianal Disease Activity Index (PDAI) were employed for evaluation.

The adjunctive use of HBOT with conventional therapy yielded significant clinical improvements in patients with Crohn's disease complicated by perianal fistulas. This was shown by an 81.8% improvement in CDAI scores and a 54.5% clinical remission rate, as determined by SESCD and PDAI. Notably, the beneficial effects of HBOT on SESCD, PDAI, and faecal calprotectin levels were statistically significant and persisted for 6 weeks post-HBOT, with sustained improvements observed in a follow-up assessment approximately 9 months after treatment.

The findings of this study suggest that HBOT may be a viable therapeutic adjunct in the management of complex cases of Crohn's disease, particularly those with recurrent symptoms and limited responsiveness to conventional treatments. HBOT demonstrated potential in improving clinical outcomes and achieving remission rates exceeding 50%, indicating its promise as a treatment modality in this patient population.

Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

The presence of perianal fistulae constitutes a more severe phenotype of Crohn's disease (CD) that often requires intensive medical therapy, wound care, and surgical intervention. Despite therapeutic advances in inflammatory bowel disease, the treatment of perianal fistulae remains challenging. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment modality for induction of fistula healing. We illustrate a case in which HBOT achieved fistula healing in a young patient with severe refractory perianal Crohn's disease (pCD). We also review the current literature and discuss the role of HBOT in the treatment armamentarium of pCD.

Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown.

CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed.

HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn's Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4.

HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab.

Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .

I read with great interest the letter by Calderón et al., who clearly described effectiveness of hyperbaric oxygen therapy (HBOT) for refractory ischemic ulcer at the ileorectal anastomosis in Crohn's disease (CD). I congratulate them on their efforts in achieving a favorable long-term outcome. I would like to share my experience of HBOT for perianal CD (PCD). In addition, I discuss recent trials of HBOT for PCD.

Inflammatory bowel diseases (IBD), with an increasing incidence, pose a significant health burden. Although there have been significant advances in the treatment of IBD, more progress is still needed. Hyperbaric oxygen therapy (HBOT) has been shown to treat a host of conditions such as carbon monoxide poisoning, decompression sickness, and gas gangrene. In the last few years, there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD. Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress, inhibiting mucosal inflammation, promoting ulcer healing, influencing gut microbes, and reducing the incidence of IBD complications. This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.

The heterogeneity in data quality presented in studies regarding Crohn's anal fistula (CAF) limit extrapolation into clinical practice. The ENiGMA collaborators established a core descriptor set to standardize reporting of CAF. The aim of this work was to quantify the use of these descriptors in recent literature.

We completed a systematic review of PubMed and the Cochrane Library, extracting publications from the past 10 years specific to the clinical interventions and outcomes of CAF, and reported in line with PRISMA guidance. Each article was assessed for inclusion of ENiGMA descriptors. The median number of descriptors per publication was evaluated along with the overall frequency of each individual descriptor. Use of ENiGMA descriptors was compared between medical and procedural publications.

Ninety publications were included. The median number of descriptors was 15 of 37; 16 descriptors were used in over half of the publications while 17 were used in fewer than a third. Descriptors were more frequently used in procedural (n = 16) than medical publications (n = 14) (p = 0.031). In procedural publications, eight descriptors were more frequently used including Faecal incontinence, Number of previous fistula interventions, Presence and severity of anorectal stenosis and Current proctitis. Medical publications were more likely to include Previous response to biological therapy and Duration and type of current course of biological therapy.

With many descriptors being used infrequently and variations between medical and procedural literature, the colorectal community should assess the need for all 37 descriptors.

Pediatric Crohn's disease commonly presents with moderate-to-severe intestinal inflammation with a greater risk of complications if remission is not achieved. Anti-tumor necrosis factor therapies have offered the possibility of deep and durable remission; however, many children do not respond or no longer respond over time. Further, some children do not require broader systemic immunosuppression to achieve remission and are better served by an alternative treatment strategy. Proper utilization of advanced biologic and small-molecule therapies, which have become available for adult patients since anti-tumor necrosis factor medications, is paramount for tighter disease control for a large proportion of children. Newer advanced therapies such as anti-integrin and anti-interleukin biologics, and several small-molecule agents capitalize on various mechanisms through narrower immunologic targets and reduced immunogenicity. Given limited regulatory approvals of these agents for use in children with Crohn's disease, clinicians continue to rely on data extrapolated from clinical trials in adult patients, sparse pediatric studies, and a growing real-world experience for treatment selection and optimization. In this article, we discuss currently available treatment options, pipeline drugs, and relevant data as they pertain to some of the most pressing clinical challenges faced in treating pediatric Crohn's disease.

Perianal Crohn's disease affects 25%-35% of patients with Crohn's disease and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health-related quality of life scores typically related to pain and fecal incontinence. In addition, patients with perianal Crohn's disease have higher rates of hospitalizations, surgeries, and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation and the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring, and a close follow-up. Surgical management is critical to drain abscesses before immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps, and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease.

Hypoxia is a known contributor to inflammation in inflammatory bowel diseases (IBD), and a growing interest has emerged in pharmacologically targeting hypoxia response pathways to treat IBD. The most basic form of treatment for hypoxia is delivering higher amounts of oxygen to the intestinal mucosa. In this review, we summarize the evidence in support of hyperbaric oxygen therapy (HBOT), a mechanism to deliver high amounts of oxygen to tissue, for treating IBD.

Two phase 2 clinical trials in hospitalized ulcerative colitis patients suffering from moderate-to-severe flares have demonstrated that HBOT improves responsiveness to steroids and avoidance of rescue medical and surgical therapy. Outpatient cohort studies in perianal fistulizing Crohn's disease and fistulizing complications of the pouch have demonstrated improved healing, particularly for complex fistulae. Several systematic reviews have now been completed, and HBOT has been observed to be well tolerated with low rates of adverse events.

HBOT may be considered as an adjunctive treatment for hospitalized ulcerative colitis flares and Crohn's disease-related fistulae. Higher quality trials are needed to confirm efficacy.

A rectovaginal fistula is a debilitating condition that often severely impacts quality of life. Despite many treatment options available, the best surgical treatment is far from being established, and many patients will undergo several procedures before fistula closure is achieved. Gracilis muscle interposition, which is the transposition of the gracilis muscle into the rectovaginal septum, is an option for complex and persistent fistulas, but literature on the subject is scarce, mainly consisting of small case series.

This study aimed to assess the success rate of gracilis muscle interposition for the surgical treatment of rectovaginal fistula.

MEDLINE, Embase, Cochrane Library, and Web of Science.

Studies comprising at least 5 patients who underwent gracilis muscle interposition for rectovaginal fistula were included. No date or language restrictions was applied.

Gracilis muscle interposition.

The primary outcome is the fistula closure rate (%). Other domains analyzed are stoma closure rate, postoperative complications, quality of life, fecal continence, and sexual function.

Twenty studies were included for a total of 384 patients. The pooled fistula closure rate for gracilis muscle interposition was 64% (95% CI, 53%-74%; range, 33%-100%). Risk factors for failure were smoking, underlying Crohn's disease, and more than 2 previous repairs, whereas stoma formation was associated with improved outcomes. Postoperative complications ranged from 0% to 37%, mostly related to surgical site occurrences at the harvest site and perineal area. No deaths occurred. Gracilis muscle interposition improved quality of life and fecal continence, but impairment of sexual function was common.

Most of the included studies were small case series.

Gracilis muscle interposition is a safe and moderately effective treatment that could be taken into consideration as second- or third-line therapy for recurrent rectovaginal fistula.

CRD42022319621.

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn's disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas.