Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer: A Randomized Clinical Trial.

Importance: Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late local toxic effects after breast irradiation. Strong evidence of effectiveness is lacking. Objective: To assess effectiveness of HBOT for late local toxic effects in women who received adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: This was a hospital-based, pragmatic, 2-arm, randomized clinical trial nested within the prospective UMBRELLA cohort following the trials within cohorts design in the Netherlands. Participants included 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction 12 months or longer after breast irradiation. Data analysis was performed from May to September 2023. Intervention: Receipt of 30 to 40 HBOT sessions over a period of 6 to 8 consecutive weeks. Main Outcomes and Measures: Breast, chest wall, and/or shoulder pain 6 months postrandomization measured by the European Organization for Research and Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were patient-reported fibrosis, edema, movement restriction, and overall quality of life. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles. Results: Between November 2019 and August 2022, 125 women (median [range] age at randomization, 56 [37-85] years) with late local toxic effects were offered to undergo HBOT (intervention arm), and 61 women (median [range] age at randomization, 60 [36-80] years) were randomized to the control arm. Of those offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity. In ITT, moderate or severe pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI, 0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75% (9.7 of 12.9) among control participants expected to complete HBOT if offered (adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49 (51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no significant differences in breast edema, movement restriction, and quality of life between groups in ITT and CACE. Conclusions and Relevance: In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller than anticipated proportion of women with late local toxic effects was prepared to undergo HBOT. Trial Registration: ClinicalTrials.gov Identifier: NCT04193722.

The Short- and Long-Term Outcome Priorities of a Western Australian Adult Burn Population.

To optimize patient recovery, understanding which outcomes are most important to burn patients is key. However, research to determine what outcomes are patient priorities is limited. Therefore, we assessed what outcomes are most important to Western Australian burn patients, separately in the short-term (<6 months) and long-term (6-24 months) after injury. Adult patients who had a burn injury 3-36 months ago completed a survey, rating the importance of 36 short- and long-term outcomes. The survey items were ranked according to the number of patients reporting the outcome as "very important." Results were compared between subgroups based on age, gender, burn size, and number of surgeries. Ninety-three patients were included. In the short-term, "not having a wound infection" (87.1%), "good wound healing" (83.9%), and "walking or moving around" (74.7%) were the most important outcomes. "Lifting or moving something" (67.6%), "walking or moving around" (66.2%), and "being independent" (66.2%) were reported as most important in the long-term. Scar-related outcomes were more important to females and to patients with multiple surgeries; mental health outcomes were priorities for females and patients with major burns; walking and moving around to males and older patients; and social and financial outcomes were rated highly by patients with major burns and multiple surgeries. In conclusion, the most important outcomes were consistent across time periods, indicating the importance of core outcomes in longitudinal follow-up. The wide range of priority outcomes and differences between subgroups underlines the need for multidisciplinary care and a patient-centered approach to support patients.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease: Results of the HOT-TOPIC trial after 1-year follow-up.

BACKGROUND: Previously published short-term results (week 16) of this trial showed a significant improvement in clinical, radiologic and biochemical outcomes in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen therapy. OBJECTIVE: To assess the long-term (week 60) efficacy, safety and feasibility of hyperbaric oxygen therapy in perianal fistula in Crohn's disease. METHODS: Crohn's disease patients with high perianal fistula(s) failing conventional treatment >6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received 40 hyperbaric oxygen sessions and outcomes were assessed at week 16 and week 60. RESULTS: Twenty patients were included (median age 34 years). At week 16, median scores of the perianal disease activity index and modified Van Assche index (co-primary outcomes) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, p < 0.001) and 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, p = 0.004), respectively. At week 60, the respective scores remained significantly lower than baseline: 4 (95% CI 3-7, p < 0.001) and 7.7 (95% CI 5.2-10.2, p = 0.003). Perianal disease activity index score of 4 or less (representing inactive perianal disease) was observed in 13 patients at week 16 and 12 patients at week 60. Using fistula drainage assessment, 12 and 13 patients showed a clinical response at week 16 and 60, respectively, and clinical remission was achieved in four patients for both time points. At week 16, a statistically significant biochemical improvement (C-reactive protein and faecal calprotectin levels) was found, but this effect was no longer significant at week 60. CONCLUSIONS: The clinical and radiologic improvement of perianal fistula in Crohn's disease, that was found at week 16 after treatment with hyperbaric oxygen therapy, is maintained at 1-year follow-up.

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease.

BACKGROUND: Positive effects of hyperbaric oxygen on perianal fistulas in Crohn's disease have been reported. AIM: To assess efficacy, safety and feasibility of hyperbaric oxygen in Crohn's disease patients with therapy-refractory perianal fistulas. METHODS: Twenty consecutive patients were recruited at the out-patient fistula clinic of the Amsterdam UMC. Crohn's disease patients with high perianal fistula(s) failing conventional treatment for over 6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received treatment with 40 hyperbaric oxygen sessions and outcome parameters were assessed at Week 16. RESULTS: Seven women and 13 men were included (median age 34 years). At Week 16, median scores of perianal disease activity index and modified van Assche index (co-primary outcome parameters) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, P < 0.001), and from 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, P = 0.004) respectively. Perianal disease activity index scores ≤4 (representing inactive perianal disease) were observed in 13/20 patients (65%). Twelve patients showed a clinical response (60%) and four (20%) clinical remission, assessed with fistula drainage assessment. Median C-reactive protein and faecal calprotectin levels decreased from 4.2 mg/mL (95% CI 1.6-8) to 2.2 (95% CI 0.9-4.3, P = 0.003) and from 399 µg/g (95% CI 52-922) to 31 (95% CI 16-245, P = 0.001), respectively. CONCLUSIONS: We found significant clinical, radiological and biochemical improvement in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen. CLINICAL TRIAL REGISTRATION: www.trialregister.nl/trial/6489.

Persistent extravascular bubbles on radiologic imaging after recompression treatment for decompression sickness: A case report.

Decompression sickness (DCS) is a condition arising when dissolved inert gas in tissue forms extravascular and/or intravascular bubbles during or after depressurisation. Patients are primarily treated with 100% oxygen and recompression, which is often assumed to lead to resolution of bubbles. After this, repeated hyperbaric exposures can be provided in case of persistent symptoms, with oxygen delivery to ischaemic tissues, anti-inflammatory properties and reduction of oedema considered the main mechanisms of action. In this case report we present the history and imaging of a diver diagnosed with DCS that was treated with two US Navy Treatment Table 6 recompressions, but who still had multiple extravascular bubbles apparent on CT-imaging after these hyperbaric treatments. Based on these findings we hypothesise that, contrary to general belief, it is possible that large extravascular bubbles can persist after definitive treatment for DCS.

Wound healing of metastatic perineal Crohn's disease using hyperbaric oxygen therapy: A case series.

BACKGROUND: Metastatic Crohn's disease (CD) is a rare manifestation of CD. It involves inflammatory skin lesions with histopathological findings (granulomas) similar to CD, without connection to the gastrointestinal tract. Hyperbaric oxygen therapy (HBO) has been suggested as a possible treatment option. OBJECTIVE: This study aimed to identify and treat a consecutive series of patients with biopsy-proven metastatic CD and monitor wound healing using prospectively acquired outcomes. METHODS: Pathology results of all patients with ongoing perineal wound-healing problems after proctectomy between 2005 and 2018 at the Amsterdam University Medical Centre were assessed for metastatic CD. Patients with a biopsy-proven diagnosis of perineal metastatic CD were offered HBO (40 daily sessions of 100% oxygen at 2.4 atmosphere absolute). Wound healing was monitored using photographs and standardised questionnaires (the Inflammatory Bowel Disease Questionnaire, EuroQol Visual Analogue Scale and the Female Sexual Function Index) at baseline and 1 and 3 months after HBO. RESULTS: Out of 13 patients in the cohort with persisting perineal wounds after proctectomy, six (46%) had biopsy results consistent with metastatic CD. Of these, three accepted treatment with HBO. All three patients were female. One patient had complete healing of her perineal wound; another patient showed initial improvement but had a flare of luminal and perineal disease at the 3-month follow-up. The third patient showed improvement solely in the questionnaires, with higher scores on all three questionnaires. CONCLUSION: A high rate of metastatic CD was found in patients with ongoing wound-healing problems after proctectomy, implying that the disease might not be as rare in these selected patients as previously thought. HBO might be beneficial in the treatment of metastatic CD.

Hyperbaric oxygen therapy for radiation-induced tissue injury following sarcoma treatment: A retrospective analysis of a Dutch cohort.

BACKGROUND AND OBJECTIVES: Sarcomas are commonly managed by surgical resection combined with radiotherapy. Sarcoma treatment is frequently complicated by chronic wounds and late radiation tissue injury (LRTI). This study aims to gain insight in the use and results of hyperbaric oxygen therapy (HBOT) for radiation-induced complications following sarcoma treatment. METHODS: All sarcoma patients treated between 2006 and 2017 in one of the five centers of the Institute for Hyperbaric Oxygen in the Netherlands were included for retrospective analysis. RESULTS: Thirty patients were included, 18 (60.0%) patients were treated for chronic wounds and 12 (40.0%) for LRTI. Two patients with chronic wounds were excluded from analysis as HBOT was discontinued within five sessions. In 11 of 16 (68.8%) patients treated for chronic wounds, improved wound healing was seen. Nine of 12 (75.0%) patients treated for LRTI reported a decline in pain. Reduction of fibrosis was seen in five of eight patients (62.5%) treated for LRTI. CONCLUSIONS: HBOT is safe and beneficial for treating chronic wounds and LRTI in the sarcoma population. Awaiting further prospective results, we recommend referring to HBOT centers more actively in patients experiencing impaired wound healing or symptoms of delayed radiation-induced tissue injury following multimodality sarcoma treatment.

Evaluation of the modified Van Assche index for assessing response to anti-TNF therapy with MRI in perianal fistulizing Crohn's disease.

BACKGROUND: Structured evaluation of magnetic resonance imaging (MRI) is important to guide clinical decisions of perianal fistulas in Crohn's disease (CD) patients. PURPOSE: To evaluate the recently developed modified Van Assche index to assess clinical responses to anti-tumor necrosis factor (TNF) therapy in patients with perianal fistulizing CD. METHODS: A search of medical records identified patients with fistulizing perianal CD who underwent baseline and follow-up MRI while receiving anti-TNF treatment. Patients were divided into clinical responders and non-responders based on physician's assessment. MRI-scans were scored using the original and modified Van Assche index and scores between baseline and follow-up were compared within clinical responders and non-responders. RESULTS: Thirty cases were included (48% female, median age 27 years). Clinical responders (n = 16) had a median modified Van Assche score of 9.6 (IQR 5.8-12.7) at baseline and 5.8 (IQR 3.5-8.5) at follow-up (p = 0.008). In non-responders (n = 14), corresponding scores were 7.7 (IQR 5.8-13.5) and 8.2 (IQR 5.8-11.5) (p = 0.624). In clinical responders, 6/16 showed no drop in modified Van Assche score at follow-up. Scores obtained with the original Van Assche index dropped between baseline and follow-up in clinical responders (13.0 vs. 9.6, p = 0.011), whereas no decrease was observed in non-responders (11.5 vs. 11.5, p = 0.324). CONCLUSIONS: While the modified Van Assche index overall decreases significantly in patients with perianal fistulas responding to anti-TNF treatment, one third of responders had unaltered scores at follow-up. Also, outcomes were comparable to the original Van Assche index. Further optimization of the modified Van Assche index is needed before application in larger studies.

Delayed treatment of frostbite with hyperbaric oxygen: a report of two cases.

Frostbite is an injury caused by the freezing of tissue, causing varied levels of tissue damage and necrosis. Case reports have shown a positive effect of hyperbaric oxygen (HBO2) in such injuries, in acute cases as well as delayed (up to 21 days) presentation with complications. In this case report we present the course of hyperbaric treatment of two patients (a brother and sister, age 58 and 62) who sustained frostbite injuries to both feet 28 days earlier while hiking in the Himalayas. They were initially treated in Nepal following local protocol; afterward their primary care in the Netherlands was managed by the Burn Centre at Maasstad Hospital in Rotterdam. Both patients were treated with daily sessions of in total 80 minutes of 100% oxygen at 2.5 atmospheres absolute. The female patient (age 62) received 25 sessions and showed a remarkable preservation of tissue and quick demarcation. Only partial surgical amputation of the second toe on the right was needed. In the male patient (age 58) both front feet were already mummified to a larger extent before start of treatment. During hyperbaric oxygen therapy 30 sessions) demarcation progressed quickly, resulting in early surgical amputation. Both patients experienced no side effects of HBO2 treatment. Given that both patients showed a quick progress and demarcation of their wounds, with remarkable tissue preservation in the female patient, we suggest that hyperbaric oxygen therapy should be considered in treating frostbite injuries, in acute as well as delayed cases, even four weeks after initial injury.