The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

BACKGROUND & AIMS: Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. METHODS: Pre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models. RESULTS: Proteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. CONCLUSIONS: HBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares.

BACKGROUND: Hyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients. AIM: To evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients. METHODS: We enrolled UC patients hospitalised for acute flares (Mayo score 6-12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen. RESULTS: We treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second-line therapy. Day 3 hyperbaric oxygen responders were less likely to require re-hospitalisation or colectomy by 3 months vs non-responders (0% vs 66%, P = 0.002). No treatment-related adverse events were observed. CONCLUSION: Hyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re-hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

Hyperbaric medicine simulation education curriculum: CNS toxicity during Treatment Table 6 and intubated ICU patient with mucous plugging.

INTRODUCTION/BACKGROUND: The incidence of complications and number of critically ill patients in hyperbaric medicine is relatively low [1]. This poses a challenge to those tasked with educating trainees as well as maintaining the skills of staff. Hyperbaric medicine fellows may not be exposed to critical patient scenarios or complications of hyperbaric medicine during a one-year fellowship. Additional staff may be unfamiliar with these situations as well. The purpose of hyperbaric simulation curriculum is to train health care providers for rare situations. To our knowledge, this hyperbaric simulation curriculum is the first published use of simulation education in the specialty of undersea and hyperbaric medicine. MATERIALS AND METHODS: Two simulation cases have been developed that involve a patient with oxygen toxicity during hyperbaric treatment as well as an ICU patient with mucous plugging. RESULTS: Medical training simulations are an effective method of teaching content and training multiple roles in Undersea and Hyperbaric Medicine. SUMMARY/CONCLUSIONS: A hyperbaric simulation curriculum is an achievable educational initiative that is able to train multiple team members simultaneously in situations that they may not encounter on a regular basis. We believe that this could be easily exported to otherinstitutions for further education.

Delayed hyperbaric oxygen therapy for severe arterial gas embolism following scuba diving: a case report.

We present the case of a 42-year-old female who was critically ill due to an arterial gas embolism (AGE) she experienced while diving in Maui, Hawaii. She presented with shortness of breath and dizziness shortly after surfacing from a scuba dive and then rapidly lost consciousness. The diver then had a complicated hospital course: persistent hypoxemia (likely secondary to aspiration) requiring intubation; markedly elevated creatine kinase; atrial fibrillation requiring cardioversion; and slow neurologic improvement. She had encountered significant delay in treatment due to lack of availability of local hyperbaric oxygen (HBO2) therapy. Our case illustrates many of the complications that can occur when a patient suffers a severe AGE. These cases may occur even without a history of rapid ascent or risk factors for pulmonary barotrauma, and it is imperative that they be recognized and treated as quickly as possible with HBO2. Unfortunately, our case also highlights the challenges in treating critically ill divers, particularly with the growing shortage of 24/7 hyperbaric chambers able to treat these ICU-level patients.

A favorable outcome despite a 39-hour treatment delay for arterial gas embolism: case report.

Cerebral arterial gas embolism (CAGE) occurs when gas enters the cerebral arterial vasculature. CAGE can occur during sitting craniotomies, cranial trauma or secondary to gas embolism from the heart. A far less common cause of CAGE is vascular entrainment of gas during endoscopic procedures. We present the case of a 49-year-old male who developed a CAGE following an esophagoduodenoscopy (EGD) biopsy. Due to a delay in diagnosis, the patient was not treated with hyperbaric oxygen (HBO2) therapy until 39 hours after the inciting event. Despite presenting to our institution non-responsive and with decorticate posturing, the patient was eventually discharged to a rehabilitation facility, with only mild left upper extremity weakness. This delay in HBO2 treatment represents the longest delay in treatment to our knowledge for a patient suffering from CAGE secondary to EGD. In addition to the clinical case report, we discuss the etiology of CAGE and the evidence supporting early HBO2 treatment, as well as the data demonstrating efficacy even after considerable treatment delay.