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Altieri G, Zilli A, Parigi TL, Allocca M, Furfaro F, Fiorino G, Cicerone C, Peyrin-Biroulet L, Danese S, D’Amico F. Dual Therapy in Inflammatory Bowel Disease. Biomolecules 2025; 15:222. [PMID: 40001525 PMCID: PMC11853240 DOI: 10.3390/biom15020222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/29/2025] [Accepted: 02/01/2025] [Indexed: 02/27/2025] Open
Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies.
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Affiliation(s)
- Gabriele Altieri
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
- Faculty of Medicine and Surgery, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
| | - Tommaso Lorenzo Parigi
- Faculty of Medicine and Surgery, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
| | - Gionata Fiorino
- Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Clelia Cicerone
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, INSERM NGERE, CHRU de Nancy, Université de Lorraine, F-54500 Vandœuvre-lès-Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
- Faculty of Medicine and Surgery, Vita Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (G.A.)
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Singh JP, Aleissa M, Drelichman ER, Mittal VK, Bhullar JS. Navigating the complexities of perianal Crohn's disease: Diagnostic strategies, treatment approaches, and future perspectives. World J Gastroenterol 2024; 30:4745-4753. [PMID: 39610776 PMCID: PMC11580605 DOI: 10.3748/wjg.v30.i44.4745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/25/2024] [Accepted: 10/24/2024] [Indexed: 11/12/2024] Open
Abstract
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.
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Affiliation(s)
- Jai P Singh
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
| | - Maryam Aleissa
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Ernesto R Drelichman
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Vijay K Mittal
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Jasneet S Bhullar
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
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3
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Tanaka HL, Rees JR, Zhang Z, Ptak JA, Hannigan PM, Silverman EM, Peacock JL, Buckey JC. Emerging Indications for Hyperbaric Oxygen Treatment: Registry Cohort Study. Interact J Med Res 2024; 13:e53821. [PMID: 39078624 PMCID: PMC11372337 DOI: 10.2196/53821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 02/17/2024] [Accepted: 07/30/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Hyperbaric oxygen (HBO2) treatment is used across a range of medical specialties for a variety of applications, particularly where hypoxia and inflammation are important contributors. Because of its hypoxia-relieving and anti-inflammatory effects HBO2 may be useful for new indications not currently approved by the Undersea and Hyperbaric Medical Society. Identifying these new applications for HBO2 is difficult because individual centers may only treat a few cases and not track the outcomes consistently. The web-based International Multicenter Registry for Hyperbaric Oxygen Therapy captures prospective outcome data for patients treated with HBO2 therapy. These data can then be used to identify new potential applications for HBO2, which has relevance for a range of medical specialties. OBJECTIVE Although hyperbaric medicine has established indications, new ones continue to emerge. One objective of this registry study was to identify cases where HBO2 has been used for conditions falling outside of current Undersea and Hyperbaric Medical Society-approved indications and present outcome data for them. METHODS This descriptive study used data from a web-based, multicenter, international registry of patients treated with HBO2. Participating centers agree to collect data on all patients treated using standard outcome measures, and individual centers send deidentified data to the central registry. HBO2 treatment programs in the United States, the United Kingdom, and Australia participate. Demographic, outcome, complication, and treatment data, including pre- and posttreatment quality of life questionnaires (EQ-5D-5L) were collected for individuals referred for HBO2 treatment. RESULTS Out of 9726 patient entries, 378 (3.89%) individuals were treated for 45 emerging indications. Post-COVID-19 condition (PCC; also known as postacute sequelae of COVID-19; 149/378, 39.4%), ulcerative colitis (47/378, 12.4%), and Crohn disease (40/378, 10.6%) accounted for 62.4% (n=236) of the total cases. Calciphylaxis (20/378, 5.3%), frostbite (18/378, 4.8%), and peripheral vascular disease-related wounds (12/378, 3.2%) accounted for a further 13.2% (n=50). Patients with PCC reported significant improvement on the Neurobehavioral Symptom Inventory (NSI score: pretreatment=30.6; posttreatment=14.4; P<.001). Patients with Crohn disease reported significantly improved quality of life (EQ-5D score: pretreatment=53.8; posttreatment=68.8), and 5 (13%) reported closing a fistula. Patients with ulcerative colitis and complete pre- and post-HBO2 data reported improved quality of life and lower scores on a bowel questionnaire examining frequency, blood, pain, and urgency. A subset of patients with calciphylaxis and arterial ulcers also reported improvement. CONCLUSIONS HBO2 is being used for a wide range of possible applications across various medical specialties for its hypoxia-relieving and anti-inflammatory effects. Results show statistically significant improvements in patient-reported outcomes for inflammatory bowel disease and PCC. HBO2 is also being used for frostbite, pyoderma gangrenosum, pterygium, hypospadias repair, and facial filler procedures. Other indications show evidence for improvement, and the case series for all indications is growing in the registry. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR2-10.2196/18857.
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Affiliation(s)
- Hideaki L Tanaka
- Division of Undersea and Hyperbaric Medicine, Department of Emergency Medicine, University of California at San Diego, San Diego, CA, United States
| | - Judy R Rees
- Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States
| | - Ziyin Zhang
- Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States
| | - Judy A Ptak
- Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | | | | | - Janet L Peacock
- Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States
| | - Jay C Buckey
- Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States
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Pacheco T, Monteiro S, Barros L, Silva J. Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer. World J Gastroenterol 2024; 30:3373-3385. [PMID: 39091713 PMCID: PMC11290399 DOI: 10.3748/wjg.v30.i28.3373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/24/2024] Open
Abstract
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.
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Affiliation(s)
- Tatiana Pacheco
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Sara Monteiro
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Luísa Barros
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Jorge Silva
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
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Dai N, Gu J, Luo Y, Tao Y, Chou Y, He Y, Qin H, Chen T, Fu X, Chen M, Xing Z. Impact of hyperoxia on the gut during critical illnesses. Crit Care 2024; 28:66. [PMID: 38429791 PMCID: PMC10905909 DOI: 10.1186/s13054-024-04848-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 02/22/2024] [Indexed: 03/03/2024] Open
Abstract
Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.
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Affiliation(s)
- Ninan Dai
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Juan Gu
- Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28, Malmö, Sweden
| | - Yanhong Luo
- First Clinical College, Zunyi Medical University, Zunyi, China
| | - Yuanfa Tao
- Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuehting Chou
- Department of Cardiopulmonary Bypass, Wuhan Asian Heart Hospital, Wuhan, China
| | - Ying He
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Han Qin
- Department of Respiratory and Critical Care Medicine, Kweichow Moutai Hospital, Guizhou Province, Zunyi, China
| | - Tao Chen
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaoyun Fu
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Miao Chen
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Zhouxiong Xing
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
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6
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Devi J, Ballard DH, Aswani-Omprakash T, Parian AM, Deepak P. Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies. Indian J Gastroenterol 2024; 43:48-63. [PMID: 38308773 DOI: 10.1007/s12664-024-01524-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/02/2024] [Indexed: 02/05/2024]
Abstract
Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.
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Affiliation(s)
- Jalpa Devi
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine in Saint Louis, 660 S. Euclid Avenue, Campus Box 8124, Saint Louis, MO, 63110, USA
| | - David H Ballard
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | | | - Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Parakkal Deepak
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine in Saint Louis, 660 S. Euclid Avenue, Campus Box 8124, Saint Louis, MO, 63110, USA.
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Dokmak A, Sweigart B, Orekondy NS, Jangi S, Weinstock JV, Hamdeh S, Kochar GS, Shen B, Levy AN. Efficacy and Safety of Hyperbaric Oxygen Therapy in Fistulizing Crohn's Disease: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2024; 58:120-130. [PMID: 37682003 DOI: 10.1097/mcg.0000000000001905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/09/2023]
Abstract
BACKGROUND Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn's disease (CD). METHODS A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" criteria. Study bias was assessed using the Cochrane Handbook guidelines. RESULTS Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I2 = 0). The risk of bias was observed across all studies. CONCLUSION HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.
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Affiliation(s)
- Amr Dokmak
- Department of Hospital Medicine, Catholic Medical Center, Manchester, NH
| | | | | | - Sushrut Jangi
- Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA
| | - Joel V Weinstock
- Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA
| | - Shadi Hamdeh
- Division of Gastroenterology, Hepatology and Motility, University of Kansas, Kansas City, KS
| | - Gursimran S Kochar
- Division of Gastroenterology, Hepatology, and Nutrition, Allegheny Health Network, Pittsburgh, PA
| | - Bo Shen
- Center for Interventional Inflammatory Bowel Disease, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, NY
| | - Alexander N Levy
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT
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8
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Bhat S, Rieder F. Hypoxia-Inducible Factor 1-Alpha Stabilizers in the Treatment of Inflammatory Bowel Diseases: Oxygen as a Novel IBD Therapy? J Crohns Colitis 2022; 16:1924-1932. [PMID: 35776532 DOI: 10.1093/ecco-jcc/jjac092] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Despite the significant advances in the medical armamentarium for inflammatory bowel diseases [IBD], current treatment options have notable limitations. Durable remission rates remain low, loss of response is common, administration routes are largely parenteral for novel biologics, and medication safety remains a concern. This explains an ongoing unmet need for safe medications with novel mechanisms of action that are administered orally. In line with these criteria, hypoxia-inducible factor [HIF]-1α stabilizers, acting via inhibition of prolyl hydroxylase enzymes, are emerging as an innovative therapeutic strategy. We herein review the mechanism of action and available clinical data for HIF-1α stabilizers and their potential place in the future IBD treatment algorithm.
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Affiliation(s)
- Shubha Bhat
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.,Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease & Surgery Institute, Cleveland Clinic, OH, USA
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease & Surgery Institute, Cleveland Clinic, OH, USA
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9
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Burtscher J, Mallet RT, Pialoux V, Millet GP, Burtscher M. Adaptive Responses to Hypoxia and/or Hyperoxia in Humans. Antioxid Redox Signal 2022; 37:887-912. [PMID: 35102747 DOI: 10.1089/ars.2021.0280] [Citation(s) in RCA: 73] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Significance: Oxygen is indispensable for aerobic life, but its utilization exposes cells and tissues to oxidative stress; thus, tight regulation of cellular, tissue, and systemic oxygen concentrations is crucial. Here, we review the current understanding of how the human organism (mal-)adapts to low (hypoxia) and high (hyperoxia) oxygen levels and how these adaptations may be harnessed as therapeutic or performance enhancing strategies at the systemic level. Recent Advances: Hyperbaric oxygen therapy is already a cornerstone of modern medicine, and the application of mild hypoxia, that is, hypoxia conditioning (HC), to strengthen the resilience of organs or the whole body to severe hypoxic insults is an important preparation for high-altitude sojourns or to protect the cardiovascular system from hypoxic/ischemic damage. Many other applications of adaptations to hypo- and/or hyperoxia are only just emerging. HC-sometimes in combination with hyperoxic interventions-is gaining traction for the treatment of chronic diseases, including numerous neurological disorders, and for performance enhancement. Critical Issues: The dose- and intensity-dependent effects of varying oxygen concentrations render hypoxia- and/or hyperoxia-based interventions potentially highly beneficial, yet hazardous, although the risks versus benefits are as yet ill-defined. Future Directions: The field of low and high oxygen conditioning is expanding rapidly, and novel applications are increasingly recognized, for example, the modulation of aging processes, mood disorders, or metabolic diseases. To advance hypoxia/hyperoxia conditioning to clinical applications, more research on the effects of the intensity, duration, and frequency of altered oxygen concentrations, as well as on individual vulnerabilities to such interventions, is paramount. Antioxid. Redox Signal. 37, 887-912.
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Affiliation(s)
- Johannes Burtscher
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Robert T Mallet
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Vincent Pialoux
- Inter-University Laboratory of Human Movement Biology EA7424, University Claude Bernard Lyon 1, University of Lyon, Lyon, France
| | - Grégoire P Millet
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
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10
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You JH, Jiang JL, He WB, Ma H, Zhou M, Chen XX, Liu QL, Huang C. Addition of hyperbaric oxygen therapy versus usual care alone for inflammatory bowel disease: A systematic review and meta-analysis. Heliyon 2022; 8:e11007. [PMID: 36276722 PMCID: PMC9583108 DOI: 10.1016/j.heliyon.2022.e11007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/29/2022] [Accepted: 10/05/2022] [Indexed: 11/22/2022] Open
Abstract
Objective Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease that includes ulcerative colitis (UC) and Crohn's disease (CD). Hyperbaric oxygen therapy (HBOT) involves breathing pure oxygen in a pressurized environment. Existing literature suggests that HBOT may be an effective therapy for IBD, but a quantitative analysis is lacking. This study aims to estimate the adjunctive role of HBOT in treating IBD and lowering its recurrence rate. Design Systematic review and meta-analysis. Methods The Cochrane Library, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases were systematically searched by two reviewers independently. Meta-analyses were performed using Review Manager (RevMan, version 5.3). A random-effects model was applied due to the heterogeneity between studies. Results Twenty-nine out of the initially identified 606 articles were covered in this review, with a total of 2151 patients (2071 for UC and 80 for CD). No randomized data of HBOT for CD were included. Among UC patients, usual care plus HBOT were more likely to achieve a clinical response than usual care alone (risk ratio [RR], 1.24; 95% confidence interval (CI), 1.17 to 1.31; P < 0.001). Subgroup analysis showed that the number of HBOT sessions had no statistically significant effect on overall efficacy (P > 0.05). The pooled data showed a lower recurrence rate in the usual care plus HBOT group (RR, 0.35; 95% CI, 0.24 to 0.53; P < 0.001). The standardized mean difference in the serum tumor necrosis factor level between HBOT and non-HBOT groups was -2.13 (95% CI, -3.09 to -1.18; P < 0.001). No severe adverse events of HBOT were observed. Conclusions HBOT might be an effective and safe adjunctive treatment for IBD. Further studies are required to investigate the optimal protocol of HBOT in IBD treatment.
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Affiliation(s)
- Jiu-hong You
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Jun-liang Jiang
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wen-bo He
- Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hui Ma
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Mei Zhou
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Xin-xin Chen
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Qiao-ling Liu
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Cheng Huang
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Dawra S, Manrai M, Kumar A, Kumar S. Hyperbaric oxygen therapy in inflammatory bowel disease: a systemic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:359-360. [PMID: 35100179 DOI: 10.1097/meg.0000000000002225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Saurabh Dawra
- Department of Gastroenterology, Command Hospital Southern Command
| | | | - Ankit Kumar
- Department of Internal Medicine, Command Hospital, Southern Command, Pune, India
| | - Satish Kumar
- Department of Internal Medicine, Command Hospital, Southern Command, Pune, India
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12
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Sawayama H, Miyamoto Y, Yoshida N, Baba H. Essential updates 2020/2021: Colorectal diseases (benign)—Current topics in the surgical and medical treatment of benign colorectal diseases. Ann Gastroenterol Surg 2022; 6:321-335. [PMID: 35634190 PMCID: PMC9130914 DOI: 10.1002/ags3.12548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/27/2021] [Indexed: 11/23/2022] Open
Abstract
The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti‐tumor necrosis factor‐α agents, but not with immunomodulators, anti‐integrin agents, and 5‐aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono‐S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short‐term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow‐up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta‐analyses from 2020‐2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.
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Affiliation(s)
- Hiroshi Sawayama
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
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Yzet C, Brazier F, Sabbagh C, Fumery M. Managing complex perianal disease after anti-TNF failure: Where to go next? CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100081. [PMID: 35106477 PMCID: PMC8784625 DOI: 10.1016/j.crphar.2022.100081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/10/2022] [Accepted: 01/10/2022] [Indexed: 12/05/2022] Open
Abstract
Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.
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Affiliation(s)
- Clare Yzet
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Franck Brazier
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Charles Sabbagh
- Digestive Surgery Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
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Alenazi N, Alsaeed H, Alsulami A, Alanzi T. A Review of Hyperbaric Oxygen Therapy for Inflammatory Bowel Disease. Int J Gen Med 2021; 14:7099-7105. [PMID: 34729019 PMCID: PMC8554584 DOI: 10.2147/ijgm.s336678] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 10/04/2021] [Indexed: 11/23/2022] Open
Abstract
IBD (inflammatory bowel disease) characterized by chronic inflammation of the gastrointestinal (GI) tract is one of the chronic diseases the prevalence of which has been increasing globally. In the past few decades, significant improvements were made in the treatments relating to IBD which have reduced the hospitalization and mortality rates; however, there is still room for improvement with other alternative therapies. HBOT (hyperbaric oxygen treatment) is one of the effective therapies used in treating various conditions including wounds, decompression sickness, stroke, etc. Several studies have reported the role of HBOT as an adjunctive treatment to IBD, while adopting conventional treatment procedures. There is an increasing trend of research in this particular area. Studies have shown that HBOT reflects its therapeutic effect by controlling inflammation, reducing oxidation stress, improving the process of cleaning damaged cells and recruiting the cells involved in repair; thereby improving the immunity response system. In this context, the purpose of this review is to summarize past clinical and experimental studies and to understand the role of hyperbaric treatment for IBD. The findings from the review have suggested that hyperbaric therapy can be an effective adjunctive approach for IBD, based on which some ideas for future clinical and research work are provided.
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Affiliation(s)
- Naif Alenazi
- Diving and Hyperbaric Medicine Department, Diving Unit, Medical Services, Dammam, Saudi Arabia
| | - Hesham Alsaeed
- Diving and Hyperbaric Medicine Department, Diving Unit, Medical Services, Dammam, Saudi Arabia
| | - Adel Alsulami
- Diving and Hyperbaric Medicine Department, Diving Unit, Medical Services, Dammam, Saudi Arabia
| | - Turki Alanzi
- Department of Health Information Management and Technology, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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