Protein tau concentration in blood increases after SCUBA diving: an observational study.

PURPOSE: It is speculated that diving might be harmful to the nervous system. The aim of this study was to determine if established markers of neuronal injury were increased in the blood after diving. METHODS: Thirty-two divers performed two identical dives, 48 h apart, in a water-filled hyperbaric chamber pressurized to an equivalent of 42 m of sea water for 10 min. After one of the two dives, normobaric oxygen was breathed for 30 min, with air breathed after the other. Blood samples were obtained before and at 30-45 and 120 min after diving. Concentrations of glial fibrillary acidic, neurofilament light, and tau proteins were measured using single molecule array technology. Doppler ultrasound was used to detect venous gas emboli. RESULTS: Tau was significantly increased at 30-45 min after the second dive (p < 0.0098) and at 120 min after both dives (p < 0.0008/p < 0.0041). Comparison of matching samples showed that oxygen breathing after diving did not influence tau results. There was no correlation between tau concentrations and the presence of venous gas emboli. Glial fibrillary acidic protein was decreased 30-45 min after the first dive but at no other point. Neurofilament light concentrations did not change. CONCLUSIONS: Tau seems to be a promising marker of dive-related neuronal stress, which is independent of the presence of venous gas emboli. Future studies could validate these results and determine if there is a quantitative relationship between dive exposure and change in tau blood concentration.

Randomised, controlled, open label, multicentre clinical trial to explore safety and efficacy of hyperbaric oxygen for preventing ICU admission, morbidity and mortality in adult patients with COVID-19.

INTRODUCTION: COVID-19 may cause severe pneumonitis and trigger a massive inflammatory response that requires ventilatory support. The intensive care unit (ICU)-mortality has been reported to be as high as 62%. Dexamethasone is the only of all anti-inflammatory drugs that have been tested to date that has shown a positive effect on mortality. We aim to explore if treatment with hyperbaric oxygen (HBO) is safe and effective for patients with severe COVID-19. Our hypothesis is that HBO can prevent ICU admission, morbidity and mortality by attenuating the inflammatory response. The primary objective is to evaluate if HBO reduces the number of ICU admissions compared with best practice treatment for COVID-19, main secondary objectives are to evaluate if HBO reduces the load on ICU resources, morbidity and mortality and to evaluate if HBO mitigates the inflammatory reaction in COVID-19. METHODS AND ANALYSIS: A randomised, controlled, phase II, open label, multicentre trial. 200 subjects with severe COVID-19 and at least two risk factors for mortality will be included. Baseline clinical data and blood samples will be collected before randomisation and repeated daily for 7 days, at days 14 and 30. Subjects will be randomised with a computer-based system to HBO, maximum five times during the first 7 days plus best practice treatment or only best practice treatment. The primary endpoint, ICU admission, is defined by criteria for selection for ICU. We will evaluate if HBO mitigates the inflammatory reaction in COVID-19 using molecular analyses. All parameters are recorded in an electronic case report form. An independent Data Safety Monitoring Board will review the safety parameters. ETHICS AND DISSEMINATION: The trial is approved by The National Institutional Review Board in Sweden (2020-01705) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative and any inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION: NCT04327505. EudraCT number: 2020-001349-37.

Biomarkers of neuronal damage in saturation diving-a controlled observational study.

PURPOSE: A prospective and controlled observational study was performed to determine if the central nervous system injury markers glial fibrillary acidic protein (GFAp), neurofilament light (NfL) and tau concentrations changed in response to a saturation dive. METHODS: The intervention group consisted of 14 submariners compressed to 401 kPa in a dry hyperbaric chamber. They remained pressurized for 36 h and were then decompressed over 70 h. A control group of 12 individuals was used. Blood samples were obtained from both groups before, during and after hyperbaric exposure, and from the intervention group after a further 25-26 h. RESULTS: There were no statistically significant changes in the concentrations of GFAp, NfL and tau in the intervention group. During hyperbaric exposure, GFAp decreased in the control group (mean/median - 15.1/ - 8.9 pg·mL-1, p < 0.01) and there was a significant difference in absolute change of GFAp and NfL between the groups (17.7 pg·mL-1, p = 0.02 and 2.34 pg·mL-1, p = 0.02, respectively). Albumin decreased in the control group (mean/median - 2.74 g/L/ - 0.95 g/L, p = 0.02), but there was no statistically significant difference in albumin levels between the groups. In the intervention group, haematocrit and mean haemoglobin values were slightly increased after hyperbaric exposure (mean/median 2.3%/1.5%, p = 0.02 and 4.9 g/L, p = 0.06, respectively). CONCLUSION: Hyperbaric exposure to 401 kPa for 36 h was not associated with significant increases in GFAp, NfL or tau concentrations. Albumin levels, changes in hydration or diurnal variation were unlikely to have confounded the results. Saturation exposure to 401 kPa seems to be a procedure not harmful to the central nervous system. TRIAL REGISTRATION: ClinicalTrials.gov NCT03192930.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial.

BACKGROUND: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. METHODS: We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. FINDINGS: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2-18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. INTERPRETATION: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. FUNDING: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.

Serum tau concentration after diving - an observational pilot study.

INTRODUCTION: Increased concentrations of tau protein are associated with medical conditions involving the central nervous system, such as Alzheimer's disease, traumatic brain injury and hypoxia. Diving, by way of an elevated ambient pressure, can affect the nervous system, however it is not known whether it causes a rise in tau protein levels in serum. A prospective observational pilot study was performed to investigate changes in tau protein concentrations in serum after diving and also determine their relationship, if any, to the amount of inert gas bubbling in the venous blood. METHODS: Subjects were 10 navy divers performing one or two dives per day, increasing in depth, over four days. Maximum dive depths ranged from 52-90 metres' sea water (msw). Air or trimix (nitrogen/oxygen/helium) was used as the breathing gas and the oxygen partial pressure did not exceed 160 kPa. Blood samples taken before the first and after the last dives were analyzed. Divers were monitored for the presence of venous gas emboli (VGE) at 10 to15 minute intervals for up to 120 minutes using precordial Doppler ultrasound. RESULTS: Median tau protein before diving was 0.200 pg·mL⁻¹ (range 0.100 to 1.10 pg·mL⁻¹) and after diving was 0.450 pg·mL⁻¹ (range 0.100 to 1.20 pg·mL⁻¹; P = 0.016). Glial fibrillary acidic protein and neurofilament light protein concentrations analyzed in the same assay did not change after diving. No correlation was found between serum tau protein concentration and the amount of VGE. CONCLUSION: Repeated diving to between 52-90 msw is associated with a statistically significant increase in serum tau protein concentration, which could indicate neuronal stress.

[The use of treatment table COMEX 30 for severe neurological decompression sickness]. / COMEX 30 för behandling av tryckfallssjuka med neurologiska symtom.

The use of treatment table COMEX 30 for severe neurological decompression sickness Decompression sickness (DCS) can occur after all dives. It often requires treatment in a pressure chamber. DCS with symptoms from the nervous system is particularly serious. In certain cases, the commonly used recompression table (USN TT6) does not suffice to revert severe neurological symptoms. A more advanced recompression table, COMEX 30, can be utilized in these cases. We report three cases of DCS where treatment according to COMEX 30 successfully resolved neurological symptoms. These cases illustrate the importance of fast and proper management of severe DCS and the need of hyperbaric centers staffed and equipped to give correct treatment. National coordination is paramount in order to be able to provide optimal care for both recreational and commercial divers afflicted by DCS.

[Fewer cases of decompression sickness in Västra Götaland. Eight years of statistics show a reduced number of consultations and treatments]. / Färre fall av dykarsjuka i Västra Götaland. Åtta års statistik visar minskat antal konsultationer och behandlingar.

During the period 2005 to 2012, a total of 340 consultations (phone calls and/or visits) regarding possible decompression illness were recorded at the two hospitals with recompression chambers in the Västra Götaland region, Sweden. An analysis of the data showed a trend towards fewer consultations and recompression treatments. A similar trend has been observed in many other countries. Possible reasons for this reduction in the number of cases are discussed. Most of the patients only present relatively mild signs and symptoms at the time of consultation. This, together with the fact that the number of patients is low, involves a risk that awareness and knowledge regarding correct handling and care in diving accidents might be lost. Since rapid and correct care of decompression illness is important to avoid later sequeale it is important that competence in diving medicine is maintained at hospitals Nationwide.

Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: a prospective cohort study on patient-perceived quality of recovery.

PURPOSE: In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. METHODS AND MATERIALS: Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. RESULTS: The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50±16 to 66±20 after treatment (P<.001) and in the bowel domain from 48±18 to 68±18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. CONCLUSIONS: HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region.