Hyperbaric Oxygen for Radiation Necrosis of the Brain.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) shows promising results in treating radionecrosis (RN) but there is limited evidence for its use in brain RN. The purpose of this study is to report the outcomes of using HBOT for symptomatic brain RN at a single institution. METHODS: This was a retrospective review of patients with symptomatic brain RN between 2008 and 2018 and was treated with HBOT. Demographic data, steroid use, clinical response, radiologic response and toxicities were collected. The index time for analysis was the first day of HBOT. The primary endpoint was clinical improvement of a presenting symptom, including steroid dose reduction. RESULTS: Thirteen patients who received HBOT for symptomatic RN were included. The median time from last brain radiation therapy to presenting symptoms of brain RN was 6 months. Twelve patients (92%) had clinical improvement with median time to symptom improvement of 33 days (range 1-109 days). One patient had transient improvement after HBOT but had recurrent symptomatic RN at 12 months. Of the eight patients with evaluable follow-up MRI, four patients had radiological improvement while four had stable necrosis appearance. Two patients had subsequent deterioration in MRI appearances, one each in the background of initial radiologic improvement and stability. Median survival was 15 months with median follow-up of 10 months. Seven patients reported side effects attributable to HBOT (54%), four of which were otologic in origin. CONCLUSIONS: HBOT is a safe and effective treatment for brain RN. HBOT showed clinical and radiologic improvement or stability in most patients. Prospective studies to further evaluate the effectiveness and side effects of HBOT are needed.

Utilisation de l'oxygénothérapie hyperbare à la suite de séances de radiothérapie entraînant la mort du tissu cérébral. Introduction: Si l'oxygénothérapie hyperbare (OHB) laisse entrevoir des résultats prometteurs dans le traitement des radionécroses (RN), les preuves demeurent limitées quant à son utilisation dans le cas de RN du cerveau. L'objectif de cette étude est de présenter des résultats de recherche liés, dans un seul établissement de santé, à l'utilisation de l'OHB dans le cas de RN symptomatiques du cerveau. Méthodes: Pour ce faire, nous avons effectué une analyse rétrospective des dossiers de patients atteints de RN symptomatiques du cerveau entre 2008 et 2018 et ayant été traités lors de séances d'OHB. Nous avons aussi recueilli des données de nature démographique et d'autres portant sur l'utilisation de stéroïdes, sur la réponse clinique et radiologique des patients et sur les toxicités. Le point de départ (index time) de notre étude a été la première séance d'OHB alors que son principal indicateur de résultat a été l'amélioration sur le plan clinique d'un symptôme particulier, ce qui a inclus une réduction des doses de stéroïdes. Résultats: Au total, treize patients atteints de RN symptomatiques ont été inclus dans cette étude. Le temps médian entre une ultime séance de radiothérapie et l'apparition de symptômes de RN a été de 6 mois. Douze patients (92 %) ont donné à voir une amélioration de leur état médical, la période médiane d'amélioration de leurs symptômes étant de 33 jours (étendue : 1­109 jours). On a observé chez un seul patient une amélioration transitoire à la suite de séances d'OHB, les symptômes de RN étant réapparus au douzième mois. Sur les huit patients ayant subi un examen d'imagerie de suivi, quatre d'entre eux ont montré des signes d'amélioration sur le plan radiologique tandis que quatre autres ont donné à voir une RN stable. Fait à noter, deux patients chez qui l'on avait observé une amélioration radiologique initiale ou une stabilité de leur état ont montré une détérioration ultérieure à la suite d'un examen d'IRM. Le taux de survie médian de ces patients et leur suivi médian ont été respectivement de 15 mois et de 10 mois. Enfin, sept d'entre eux ont signalé des effets secondaires attribuables à l'OHB, dont quatre d'origine otologique. Conclusions: L'OHB demeure un traitement efficace et sécuritaire dans le cas des RN du cerveau. Elle a permis d'observer chez la plupart des patients une amélioration clinique et radiologique ou à tout le moins une stabilité de leurs symptômes. Cela dit, des études prospectives sont nécessaires afin de pouvoir évaluer plus en profondeur son efficacité et ses effets secondaires.

Hyperbaric oxygen therapy as a sole agent is not immunosuppressant in a highly immunogenic mouse model.

Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

Hyperbaric oxygen therapy and diabetic foot ulcers: knowledge and attitudes of Canadian primary care physicians.

OBJECTIVE: To explore physicians' knowledge of and attitudes toward hyperbaric oxygen therapy (HBOT) in order to better understand current diabetic foot ulcer management practices and to determine potential barriers to HBOT use. DESIGN: A 24-item questionnaire. SETTING: Primary Care Today conference in Toronto, Ont, in May of 2006. PARTICIPANTS: Physician attendees, 313 of whom completed the survey. MAIN OUTCOME MEASURES: Self-reported knowledge of and attitudes toward HBOT. RESULTS: Less than 10% of respondents had a good knowledge of HBOT, but 57% had a good attitude toward HBOT. Knowledge of and attitude toward HBOT were positively correlated (P < .0001). Good knowledge of HBOT was associated with sex (P = .0334), age younger than 40 years (P = .0803), years in medical practice (P = .0646), patient requests for HBOT referrals (P = .0127), and having previously referred patients for HBOT (P < .001). Twenty years or more in medical practice (P = .0593) and receiving patient requests for HBOT (P = .0394) were multivariate predictors of having good knowledge of HBOT. Good attitude toward HBOT was associated with age younger than 40 years (P = .0613) and having previously referred patients for HBOT (P = .0013). Multivariate analysis showed that male physicians (P = .0026) received more patient requests for HBOT (P < .0001), had good knowledge (P = .0129) and a good attitude (P = .0488), and were more likely to refer patients for HBOT. CONCLUSION: Primary care physicians have underdeveloped knowledge of HBOT, but their generally positive attitudes toward its use suggest that they might be receptive to educational interventions. Educating both physicians and patients about HBOT, specifically its cost-effectiveness, might encourage future use.

Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes.

OBJECTIVES: The aim of this study was to assess the possible effect of hyperbaric oxygen (HBO) on the healing of critical-sized defects that were grafted with demineralized bone matrix (DBM) combined with Pluronic F127 (F127) to form a gel or putty, or a commercially available biphasic calcium phosphate (BCP), mixed either with blood or F127 to form a putty. STUDY DESIGN: Twenty New Zealand White rabbits were randomly divided into 2 groups of 10 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 40 critical-sized defects. Group I defects were grafted with either DBM putty or DBM gel. Group II defects were grafted with either BCP or BCP putty. Five animals from each group received HBO treatment (100% oxygen, at 2.4 ATA) for 90 minutes per day 5 days a week for 4 weeks. The other 5 animals in each group served as a normobaric (NBO) controls, breathing only room air. All animals were humanely killed at 6 weeks. The calvariae were removed and analyzed by micro computed tomography (mCT) and histomorphometry. RESULTS: mCT analysis indicated a higher bone mineral content (BMC, P < .05), bone volume fraction (BVF; P < .001), and bone mineral density (BMD; P < .001) of the defects grafted with BCP rather than DBM. Furthermore, the voxels that were counted as bone had a higher tissue mineral density (TMD) in the BCP- than in the DBM-filled defects (P < .001). Histologically complete bony union over the defects was observed in all specimens. Histomorphometric analysis showed that DBM-filled defects had more new bone (P < .007) and marrow (P < .001), and reduced fibrous tissue compared with the BCP defects (P < .001) under NBO conditions. HBO treatment reduced the amount of fibrous tissue in BCP filled defects (P < .05), approaching levels similar to that in matching DBM-filled defects. HBO also resulted in a small but significant increase in new bone in DBM-grafted defects (P < .05). CONCLUSION: Use of DBM or BCP promoted healing in these critical-sized defects. Hyperbaric oxygen therapy resulted in a slight increase in new bone in DBM-grafted defects and much larger reduction in fibrous tissue and matching increases in marrow in BCP-grafted defects, possibly through increased promotion of angiogenesis.

Bisphosphonate associated osteonecrosis of the jaw.

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized defects.

OBJECTIVES: This study was undertaken to evaluate the effect of hyperbaric oxygen (HBO) on the repair of critical-sized defects in the presence and absence of a nonvascularized autogenous bone graft. STUDY DESIGN: Ten New Zealand White rabbits were randomly divided into 2 groups of 5 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 20 critical-sized defects. Autogenous bone grafts (ABG) were allocated to the left or right defect of each animal. Group 1 received HBO treatment at 2.4 ATA 100% oxygen for 90 minutes per day 5 days a week for 4 weeks. Group 2 served as a normobaric (NBO) control, breathing only room air. The animals in each group were humanely killed at 6 weeks. Calvaria were analyzed by micro-CT and histomorphometry. RESULTS: Micro-CT analysis indicated that as expected there was a higher bone mineral density (BMD) and bone mineral content (BMC) in ABG than unfilled defects (P < .05). However, there was a significant decline in the bone mineral content (BMC) of HBO-treated grafted defects compared to NBO-treated grafted defects (P < .05). Histologically complete bridging of the defect was observed in both NBO and HBO ABG grafted defects. Histomorphometic analysis showed that HBO treatment increased new bone and marrow, and reduced fibrous tissue in the defects (P < .01 for all). Examination of residual graft showed a near significant reduction in residual graft volume (11.2 +/- 4.7 versus 19.1 +/- 7.7, HBO versus NBO P = .085) in the HBO group. The use of a graft increased new bone and marrow in the NBO group (P < .001 for both); however, in the HBO-treated animals the differences between grafted and ungrafted were not significant. CONCLUSION: HBO enhances bony healing in ungrafted rabbit calvarial critical-sized defects and may increase the rate of residual graft resorption in autogenous bone-grafted defects.

Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw.

OBJECTIVE: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. METHODS: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RESULTS: RECOMMENDATIONS regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies. RECOMMENDATIONS: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated. CONCLUSION: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.

Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects.

BACKGROUND: Hyperbaric oxygen therapy (HBO) promotes osseous healing, however the mechanism by which this occurs has not been elucidated. HBO may promote angiogenesis, which is vital for bone healing. Vascular endothelial growth factor (VEGF) is one of the key factors that stimulates angiogenesis. OBJECTIVE: The objective of this study was to investigate whether HBO altered VEGF expression during bone healing. METHODS AND MATERIALS: Archived samples from calvarial defects of rabbits exposed to HBO (2.4 ATA, 90 minutes a day, 5 days a week for 4 weeks) and normobaric oxygen controls (NBO) were analyzed by immunohistochemistry. RESULTS: VEGF expression in 6-week HBO samples was elevated compared to NBO (P = .012). Staining of the 12-week HBO samples was reduced compared to 6-week HBO (P = .008) and was similar to 6- and 12-week NBO control samples. CONCLUSION: HBO therapy resulted in increased VEGF expression in the defects even 2 weeks after the termination of treatment (6 weeks postsurgery).

A review of bisphosphonate-associated osteonecrosis of the jaws and its management.

Bisphosphonate-associated osteonecrosis (BON) may result in serious oral complications, such as osteomyelitis and chronic exposure of necrotic bone. Dentists must be familiar with this disorder and pay special attention to all patients on bisphosphonate therapy due to their defective osteoclast function and reduced osseous tissue vascularity, leading to impaired wound healing. The purpose of this paper is to review the history and pathogenesis of BON, discuss its differential diagnosis, provide guidance to dentists on possible measures to prevent BON and review the management of patients with BON.

Ischemic scleroderma wounds successfully treated with hyperbaric oxygen therapy.

Hyperbaric oxygen therapy (HBOT) has been used to treat refractory wounds for the last several decades, with the majority of research focusing on wounds secondary to arterial insufficiency. We describe 2 patients with scleroderma with intractable bilateral extremity ulcers. Local ischemia was identified using transcutaneous oximetry. Each patient then underwent 30 treatments of HBOT at a relative depth of 2.4 ATA with resulting wound healing. This is the first reported successful use of HBOT to treat scleroderma ulcers, and may represent an unrecognized treatment option for these notoriously difficult chronic wounds.

Hyperbaric oxygen results in an increase in rabbit calvarial critical sized defects.

OBJECTIVE: This study was undertaken to evaluate whether the effects of hyperbaric oxygen (HBO) therapy could alter the critical size for spontaneous healing of a bone defect in the rabbit calvarial model. STUDY DESIGN: An animal trial of 12 weeks duration was conducted using 20 New Zealand white rabbits, which were randomly divided into 2 groups of 10 animals each. Calvarial defects were created in the parietal bones of each animal bilaterally. Defects were critical-sized, 15 mm on one side and supra-critical-sized, 18 mm on the contralateral side. Group 1 received a 90-min HBO treatment sessions at 2.4 absolute atmospheric pressure (ATA) per day for 20 consecutive days. Group 2 served as a control without any HBO treatment sessions. Five animals in each group were sacrificed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens, post-sacrifice radiographs, as well as histomorphometric analysis to compute the amount of regenerated bone within the defects. ANOVA and paired sample t test were used for statistical analysis. RESULTS: Both radiographic analysis and histomorphometric analysis demonstrated that HBO-treated animals had significantly more new bone within their defects compared with the control group (P < .001). There was no statistically significant difference between the percentage of new bone forming in the 15-mm and 18-mm HBO-treated defects. There was no difference between the 6-week and the 12-week HBO-treated groups. HBO is effective in enhancing the bony healing of full thickness critical sized as well as supra-critical-sized defects in the rabbit calvarial model. CONCLUSION: Bone regeneration was significantly greater in the HBO-treated animals regardless of the defect size. HBO may have increased the diameter of the rabbit critical-sized calvarial defect to more than 18 mm.

Treatment of radiation proctitis with hyperbaric oxygen.

BACKGROUND AND PURPOSE: Radiation proctitis is a potential complication following pelvic radiation therapy. There are no standard treatments and treatment outcomes are unpredictable. We report our experience with the use of hyperbaric oxygen treatment (HBOT) for radiation proctitis cases refractory to standard medical or laser therapy. PATIENTS AND METHODS: During the period 2000-2004, 10 patients with radiation proctitis were treated with HBOT (three males and seven females; mean age of 65). The median follow-up period was 25 months (range 6-43 months). Patient symptoms were retrospectively scored prior to, and following HBOT, based on the LENT-SOMA scale. RESULTS: Prior to treatment, three patients had Grade 3 toxicity (i.e. requiring blood transfusions) and seven had Grade 2 toxicity with dominant symptoms of rectal pain and/or diarrhoea. HBOT was well tolerated and 9 of the 10 patients completed a full HBOT treatment program. Rectal bleeding completely stopped in four of nine symptomatic patients and improved in three others. Rectal pain completely remitted in three of five symptomatic patients. Diarrhea remitted completely in one of five patients and improved in three others. Of the 10 patients treated, only two did not respond to HBOT. CONCLUSIONS: Significant improvement of rectal bleeding, diarrhea and rectal pain is possible using HBOT. HBOT should be offered to patients who fail conventional treatments for radiation proctitis.

MEASURE: A proposed assessment framework for developing best practice recommendations for wound assessment.

The effective management of nonhealing wounds is based on a complete patient history, a detailed initial assessment of the wound, and an analysis of probable causative factors. This information is used to individualize a management strategy to the underlying pathophysiology preventing healing and to implement appropriate wound interventions. Regular reassessment of progress toward healing and appropriate modification of the intervention are also necessary. Accurate and clinically relevant wound assessment is an important clinical tool, but this process remains a substantial challenge. Wound assessment terminology is nonuniform, many questions surrounding wound assessment remain unanswered, agreement has yet to be reached on the key wound parameters to measure in clinical practice, and the accuracy and reliability of available wound assessment techniques vary. This article, which resulted from a meeting of wound healing experts in June 2003, reviews clinically useful wound measurement approaches, provides an overview of the principles and practice of chronic wound assessment geared to a clinical audience, and introduces a simple mnemonic, MEASURE. MEASURE encapsulates key wound parameters that should be addressed in the assessment and management of chronic wounds: Measure (length, width, depth, and area), Exudate (quantity and quality), Appearance (wound bed, including tissue type and amount), Suffering (pain type and level), Undermining (presence or absence), Reevaluate (monitoring of all parameters regularly), and Edge (condition of edge and surrounding skin). This article also provides some preliminary recommendations targeted to developing best practice guidelines for wound assessment.