Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy.

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.

Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

The role of routine pulmonary imaging before hyperbaric oxygen treatment.

Respiratory injury during or following hyperbaric oxygen treatment (HBOT) is rare, but associated pressure changes can cause iatrogenic pulmonary barotrauma with potentially severe sequelae such as pneumothoraces. Pulmonary blebs, bullae, and other emphysematous airspace abnormalities increase the risk of respiratory complications and are prevalent in otherwise healthy adults. HBOT providers may elect to use chest X-ray routinely as a pre-treatment screening tool to identify these anomalies, particularly if a history of preceding pulmonary disease is identified, but this approach has a low sensitivity and frequently provides false negative results. Computed tomography scans offer greater sensitivity for airspace lesions, but given the high prevalence of incidental and insignificant pulmonary findings among healthy individuals, would lead to a high false positive rate because most lesions are unlikely to pose a hazard during HBOT. Post-mortem and imaging studies of airspace lesion prevalence show that a significant proportion of patients who undergo HBOT likely have pulmonary abnormalities such as blebs and bullae. Nevertheless, pulmonary barotrauma is rare, and occurs mainly in those with known underlying lung pathology. Consequently, routinely using chest X-ray or computed tomography scans as screening tools prior to HBOT for low-risk patients without a pertinent medical history or lack of clinical symptoms of cardiorespiratory disease is of low value. This review outlines published cases of patients experiencing pulmonary barotrauma while undergoing pressurised treatment/testing in a hyperbaric chamber and analyses the relationship between barotrauma and pulmonary findings on imaging prior to or following exposure. A checklist and clinical decision-making tool based on suggested low-risk and high-risk features are offered to guide the use of targeted baseline thoracic imaging prior to HBOT.

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Peripheral Auditory Function in Young HIV-Positive Adults With Clinically Normal Hearing.

OBJECTIVE: Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. STUDY DESIGN: Matched cohort study with repeated measures. SETTING: Infectious disease center in Dar es Salaam, Tanzania. METHODS: Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. RESULTS: HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. CONCLUSION: Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

A Rare Presentation of Intraosseous Sarcoidosis of the Mandible Presenting as Peri-Implantitis: A Case Report and Literature Review.

We describe a rare case of intraosseous sarcoidosis initially presenting as peri-implantitis, perform a review and analysis of 27 cases of intraosseous sarcoidosis, and provide a clinical review of this condition. We searched the literature for patients presenting with intraosseous sarcoidosis of the jaw through June 2020 using key phrases. Additional papers were included via a search of references and citing papers. Data including patient demographic characteristics and diagnostic tests were manually extracted from the cases and then qualitatively coded by the authors. Descriptive statistical analysis was performed to elucidate general themes and characteristics. A total of 27 cases, dating as early as 1943 and as recent as this case, were identified in the literature, including our case. The average age of these patients was 39 years old, with a range of 16 to 75 years. Eighteen (67%) cases were identified as female and nine (33%) as male. Fourteen cases were reported with localized mandibular involvement. Ten had maxillary disease; 3 cases were generalized to both regions. Nine cases presented anteriorly, 12 posteriorly, and 6 extended across both regions. Eight patients received surgical interventions, such as tooth extractions or lesion removal. Five patients received nonsurgical interventions, such as steroids. Ten patients received combination therapy, often involving surgical intervention and steroid therapy. Our patient had an unusual presentation of intraosseous sarcoidosis mimicking peri-implantitis. To our knowledge, no case in the English literature describes a patient with sarcoidosis presenting with peri-implantitis. Based on the literature review and analysis of our patient's experience, sarcoidosis should be considered on the differential diagnosis for patients with persistent, nonhealing bony lesions in the maxillofacial region, particularly when patients have not been exposed to osteoclast inhibitory therapy or radiation. Pathologic analysis of bone and surrounding tissue in these scenarios is essential.

The Correlation Between Body Weight and Intraocular Pressure.

INTRODUCTION: Preflight body weight is a strong predictor of visual changes in spaceflight. To understand the effect of body weight on the eye, we examined the effect of increased body mass index on intraocular pressure on Earth.METHODS: We conducted a systematic review to summarize the relationship between weight parameters (including body mass index (BMI) and obesity indices), and intraocular pressure (IOP). Study selection and data extraction were performed in duplicate using EMBASE, MEDLINE, and CENTRAL, from database inception to the second week of April 2020.RESULTS: A total of 66 individual studies were included for qualitative analysis from the 1364 studies eligible for title and abstract screening. A total of 39 studies were available for quantitative analysis. The average BMI was 25.9 (range, 20.148.8) and the average IOP was 14.9 mmHg (range, 11.627.8). The overall pooled RR between BMI and elevated intraocular pressure (IOP) was 1.06 (95 CI%, 1.041.07), meaning for each unit increase in BMI one is 6 more likely of having higher IOP than baseline. Two studies assessed the effects of bariatric surgery, and both showed significant decreases in IOP postoperatively.CONCLUSION: A higher BMI was associated with increased IOP in ground-based studies. IOP also decreased with weight loss. These data support the idea that alterations in body weight affect intraocular pressures. Further research is needed to understand the relationship between body weight, IOP, and microgravity-induced visual changes. This finding may also be useful clinically.Khan S, Kirubarajan A, Lee M, Pitha I, Buckey JC Jr. The correlation between body weight and intraocular pressure. Aerosp Med Hum Perform. 2021; 92(11):886-897.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Development of an International, Multicenter, Hyperbaric Oxygen Treatment Registry and Research Consortium: Protocol for Outcome Data Collection and Analysis.

BACKGROUND: Hyperbaric oxygen (HBO2)-oxygen at pressures higher than atmospheric-is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO2's main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO2 has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO2 therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO2 outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established. OBJECTIVE: The aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium. METHODS: A consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry. RESULTS: Early results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement. CONCLUSIONS: The registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18857.

Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.

OBJECTIVES: Hearing loss from ototoxicity is often most pronounced at high frequencies. To improve patient monitoring and compliance, high-frequency testing methods should be short and easy to administer. We evaluated the repeatability and accuracy of a Békésy-like, fixed-level frequency threshold (FLFT) technique. This test takes less than a minute and could provide a rapid and effective way to determine the highest audible frequency. We hypothesized the FLFT test would be repeatable in normal-hearing subjects, and accurate when compared with Békésy fixed-frequency audiometry in the sensitive region for ototoxicity (SRO). DESIGN: Twenty-nine normal-hearing subjects (20 females, 9 males) performed 2 different automated audiometry tests at least 4 times over a period of no less than 3 weeks. Ages ranged from 23 to 35 years (average = 28 years). Subjects completed testing under Sennheiser HDA-200 headsets. Initial fixed-frequency audiometry thresholds were obtained at frequencies ranging from 0.5 to 20 kHz to identify each subject's highest audible frequency, which was used to determine the SRO. The SRO was defined as the seven frequencies at and below the highest audible frequency in 1/6-octave steps. These frequencies were monitored with fixed-frequency audiometry. At each session, the FLFT test was administered at 80 dB SPL. Subjects used a Békésy-style tracking method to determine the frequency threshold. All testing was completed in a sound booth (single wall, Industrial Acoustics Company) using a computerized, laptop-based, system. FLFT repeatability was calculated as the root mean square difference from the first test session. FLFT accuracy was calculated as the difference from the highest audible frequency determined from fixed-frequency audiometry interpolated to 80 dB SPL level. RESULTS: The FLFT average RMSD for intersession variability was 0.05 ± 0.05 octaves. The test showed no learning effect [F(3,78) = 0.7; p = 0.6]. The overall intersession variability for SRO fixed-frequency audiometry thresholds at all frequencies was within clinically acceptable test-retest variability (10 dB) at 5.8 dB (range 2.7 to 9.9 dB). The SRO fixed-frequency audiometry therefore served as a repeatable basis of comparison for accuracy of the FLFT test. The mean absolute difference between the fixed-frequency audiometry and FLFT-determined highest audible frequency was 0.03 octaves. The FLFT and the highest audible frequency via fixed-frequency audiometry at 80 dB SPL were not different statistically (p = 0.12). The FLFT took approximately 30 seconds to complete, compared with approximately 4.5 min for fixed-frequency audiometry SRO and 20 to 25 min for a traditional ototoxic audiometric assessment. CONCLUSIONS: The Békésy-style FLFT was repeatable within 1/12 octave (1 step size in the testing procedure). The FLFT agreed well with the highest audible frequency determined via fixed-frequency audiometry at 80 dB SPL. The FLFT test is amenable to automatic and self-administration and may enable quick, accurate, noise-tolerant ototoxicity, and high-frequency hearing monitoring.

Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.

PURPOSE: To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival. RESULTS: Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. CONCLUSIONS: While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.

Hyperbaric oxygen for patients with above-knee amputations, persistent ischemia, and nonreconstructable vascular disease.

We describe four patients with above-knee amputations whose stump wounds failed to heal. After numerous revascularization attempts, these patients were diagnosed with nonreconstructable pelvic and groin vascular disease and were facing hip disarticulation. With the addition of hyperbaric oxygen treatment to vigilant wound care and negative pressure therapy, these patients healed their amputation stumps and were fit with prostheses. At their most recent follow-up, all patients were ambulating and using their prostheses.

Unusual neurological syndrome induced by atmospheric pressure change.

BACKGROUND: We describe a case of a 46-yr-old female who developed hypertension, tachycardia, dysarthria, and leg weakness provoked by pressure changes associated with flying. Typically during the landing phase of flight, she would feel dizzy and note that she had difficulty with speech and leg weakness. After the flight the leg weakness persisted for several days. The symptoms were mitigated when she took a combined alpha-beta blocker (labetalol) prior to the flight. CASE STUDY: To determine if these symptoms were related to atmospheric pressure change, she was referred for testing in a hyperbaric chamber. She was exposed to elevated atmospheric pressure (maximum 1.2 ATA) while her heart rate and blood pressure were monitored. Within 1 min she developed tachycardia and hypertension. She also quickly developed slurred speech, left arm and leg weakness, and sensory changes in her left leg. She was returned to sea level pressure and her symptoms gradually improved. A full neurological workup has revealed no explanation for these findings. She has no air collections, cysts, or other anatomic findings that could be sensitive to atmospheric pressure change. DISCUSSION: The pattern is most consistent with a vascular event stimulated by altitude exposure. This case suggests that atmospheric pressure change can produce neurological symptoms, although the mechanism is unknown.

Animal surgery during spaceflight on the Neurolab Shuttle mission.

INTRODUCTION: A surgical procedure has never been required or performed on a human in space. Parabolic microgravity simulations have suggested that surgery would be technically feasible during spaceflight. PROCEDURES: Survival surgery was performed for the first time on rats during the STS-90 Neurolab Shuttle mission. Craniotomy, leg dissection, thoracotomy, laminectomy, and laparotomy were performed as a part of physiological investigations. RESULTS: Surgical techniques successfully demonstrated in rats during spaceflight included general anesthesia, wound closure, wound healing, hemostasis, control of surgical fluids, operator restraint, and control of surgical instruments. No decrement in manual dexterity was noted by the crew, although operative time was longer compared with ground experience due to the need to maintain restraint of surgical supplies and instruments. CONCLUSIONS: The demonstration that technically demanding dissections could be accomplished successfully in space on rats suggests that comparable complex surgical procedures should be feasible on humans, if necessary, on future long-duration missions.

Black magic and EPR oximetry: from lab to initial clinical trials.

EPR oximetry is a technique that can make repeated non-invasive measurements of the PO2 in tissues. To extend the application of EPR oximetry to humans, India ink is the probe of choice because appropriate India inks have EPR signals whose line widths are sensitive to changes in oxygen concentrations, and, most importantly, India ink already has been used extensively in humans as a marker in the skin, lymphatics, various organs during surgery, tumors, and for decoration as tattoos. We have developed an India ink that has good sensitivity to oxygen, high stability in tissues, good signal intensity, and minimal toxicity. In this article we describe the various properties of this India ink, results obtained from our animal experiments, and our first preliminary clinical results, which are part of the first systematic clinical use of EPR oximetry. The clinical results indicate that it is possible to do repeated measurements over several months and probably years after the injection of the ink, indicating that long-term follow-up studies are feasible. We are very encouraged with these results and are confident that EPR oximetry using India ink will be a non-invasive, fast, and reliable technique for pO2 measurements in clinical studies.