Levels of small extracellular vesicles in patients treated with hyperbaric oxygenation.

Introduction: Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL). Material and methods: Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids. Results: We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01). Conclusions: The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

Comment on Muth et al. Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review. Medicina 2023, 59, 800.

We first want to thank the authors of the excellent review for their contributions to summarizing the confounders associated with critical flicker fusion frequency (CFFF) [...].

Effectiveness of hyperbaric chamber ventilation.

INTRODUCTION: Hyperbaric chamber ventilation (HCV) refers to the intentional introduction of fresh gas, whether air, oxygen, or heliox, into a pressurised hyperbaric chamber in order to remove stale or otherwise compromised gas. The minimum required continuous HCV rate is usually determined by mathematical models derived from the contaminant mass balance within a well-stirred compartment. Non-uniform contaminant distribution patterns inside a hyperbaric chamber could emerge and invalidate the predictions of well-stirred models. METHODS: Contaminant distribution was investigated inside a clinical hyperbaric chamber with the aim of comparing well-stirred model predictions with the actual contaminant concentration measurements. RESULTS: Local ventilation effectiveness inside a clinical hyperbaric chamber may be compromised, leading to higher contaminant concentration values compared to the predictions of a mathematical model with a well-stirred assumption. CONCLUSIONS: A well-stirred assumption in mathematical models is a useful simplification that allows reasonably accurate estimates of HCV requirements. However, local ventilation effectiveness values in a particular hyperbaric chamber might vary, with the potential for hazardous contaminant accumulation in under-ventilated zones.

Cognitive Functions in Scuba, Technical and Saturation Diving.

Scuba diving as a recreational activity is becoming increasingly popular. However, the safety of this activity, especially in the out-of-comfort zone, has been discussed worldwide. The latest publications bring conclusions regarding negative effects on cognitive functions. We compare the acute and chronic effects of diving on cognitive functioning depending on the type of dive performed, including recreational, technical and saturation diving. However, the results of research show that acute and chronic effects on cognitive functions can be negative. While acute effects are reversible after the ascent, chronic effects include white matter lesions in magnetic resonance imaging scans. We believe that more investigations should be performed to determine the chronic effects that could be observed after a few months of observations in a group of regular, intense divers. In addition, publications referring to technical divers are very limited, which is disquieting, as this particular group of divers seems to be neglected in research concerning the effects of diving on cognitive functions.

Reply to Vrijdag et al. Comment on "Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. Medicina 2021, 57, 1096".

Thank you very much for your interest and comments [...].

Impact of Hyperbaric Oxygen Therapy on Cognitive Functions: a Systematic Review.

Hyperbaric oxygen therapy (HBOT) is a modality of treatment in which patients inhale 100% oxygen inside a hyperbaric chamber pressurised to greater than 1 atmosphere. The aim of this review is to discuss neuropsychological findings in various neurological disorders treated with HBOT and to open new perspectives for therapeutic improvement. A literature search was conducted in the MEDLINE (via PubMed) database from the inception up 10 May 2020. Eligibility criteria included original articles published in English. Case studies were excluded. Full-text articles were obtained from the selected studies and were reviewed on the following inclusion criteria (1) performed cognitive processes assessment (2) performed HBOT with described protocol. Two neuropsychologists independently reviewed titles, abstracts, full texts and extracted data. The initial search retrieved 1024 articles, and a total of 42 studies were finally included after applying inclusion and exclusion criteria. The search yielded controversial results with regard to the efficiency of HBOT in various neurological conditions with cognitive disturbance outcome. To the best of our knowledge this is the first state-of-the art, systematic review in the field. More objective and precise neuropsychological assessment methods are needed to exact evaluation of the efficacy of HBOT for neuropsychological deficits. Future studies should widen the assessment of HBOT effects on different cognitive domains because most of the existing studies have focussed on a single process. Finally, there is a need for further longitudinal studies.

Effectiveness of Hyperbaric Oxygen Therapy in SARS-CoV-2 Pneumonia: The Primary Results of a Randomised Clinical Trial.

Mortality in COVID-19 is mainly associated with respiratory failure, cytokine storm, and macrophage activation. Oxygenation and anti-inflammatory effects of Hyperbaric Oxygen Therapy (HBOT) suggest that it is a promising adjunct treatment for COVID-19. Repeated sessions of HBO with standard COVID-19 therapy were used to reduce the inflammation and increase oxygenation. We evaluated the safety and efficacy of HBOT in avoiding the replacement ventilation and/or ECMO and its effect on the inflammatory process. Twenty-eight moderate-to-severe COVID-19 patients were randomized into control or HBOT group. HBOT patients participated in 5 hyperbaric sessions (60 min). Before and after each session blood gas levels and vital parameters were monitored. Blood samples were collected for extended biochemical tests, blood morphology and immunological assays. There were 3 deaths in the control, no deaths in the HBOT group. No adverse events leading to discontinuation of HBOT were observed and patients receiving HBOT required lower oxygen delivery. We observed decrease in CRP, ferritin and LDH and increase in CD3 in HBOT group compared to control. This study confirmed the feasibility and safety of HBOT in patients with COVID-19 and indicated HBOT can lead to alleviation of inflammation and partial restoration of T cell responses.

Septic Shock Induced by Vibrio Vulnificus in Northern Poland, a Case Report.

INTRODUCTION: Vibrio vulnificus infections are a growing problem worldwide. In recent years, infections with this bacteria have been reported in Central Europe, especially in the German Baltic coast but also in France and Italy. Climate warming causes the sea temperature to increase every year, which translates to an increased risk of infections from the Vibrio group. Most of these are mild and present as wound infections, but some patients develop life-threatening sepsis from either ingestion of infected mollusks or wound lesions that develop into generalized infections. Illness may be associated with necrotizing fasciitis and may require several weeks of therapy, often based on a surgical operation, demarcation of necrosis or limb amputation. A case such as the one described in this manuscript has not been previously described in Poland and demonstrates the need for a multidisciplinary approach to infection with Vibrio vulnificus. CASE PRESENTATION: A 68-year-old patient was pricked with an unknown object in the side of a lower limb during his stay at the Polish seaside. He developed a life-threatening infection in the form of severe sepsis with multiple organ failure. He required broad-spectrum antibiotic therapy, and after obtaining results for Vibrio vulnificus targeted therapy, a surgical operation with skin lesion decompression and fasciotomy was performed. Finally, hyperbaric chamber therapy was given. The patient's general condition improved, and local changes and his vital parameters stabilized. CONCLUSION: Vibrio vulnificus infection may be confused with other causes of skin and subcutaneous tissue infection, although it requires a different approach and different targeted antibiotic therapies. This infection may take the form of a life-threatening disease requiring a multidisciplinary approach.

Effect of Hyperbaric Oxygenation on Blood Cytokines and Arginine Derivatives; No Evidence for Induction of Inflammation or Endothelial Injury.

(1) Background: Hyperbaric oxygen therapy (HBOT) uses 100% oxygen delivered at 1.5-3 times the atmospheric pressure in a specialised chamber to achieve supraphysiological oxygen tension in blood and tissues. Besides its target, HBOT may affect inflammation, endothelial function or angiogenesis. This study analysed the effect of HBOT on blood concentrations of factors that may affect these processes in patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) and idiopathic sudden sensory neural hearing loss (ISSNHL). (2) Methods: Concentrations asymmetric dimethylarginine (ADMA) and other arginine derivatives were measured with liquid chromatography/mass spectrometry, whereas ELISA was used to quantitate vascular endothelial growth factor (VEGF) and cytokines (IL-1, IL-4, IL-6, IL-10, TGF-ß) before and after HBOT in 80 patients (NSTI n = 21, ISSNHL n = 53, ABN n = 6). (3) Results: While some differences were noted between patient groups in ADMA and other arginine derivatives as well as in cytokine concentrations, HBOT did not affect any of these parameters. (4) Conclusions: While cytokines and arginine derivatives concentrations were modified by underlying pathology, hyperbaric oxygenation did not immediately modify it suggesting that it is neutral for inflammation and is not inducing endothelial injury.

Oxygen: A Stimulus, Not "Only" a Drug.

Depending on the oxygen partial pressure in a tissue, the therapeutic effect of oxygenation can vary from simple substance substitution up to hyperbaric oxygenation when breathing hyperbaric oxygen at 2.5-3.0 ATA. Surprisingly, new data showed that it is not only the oxygen supply that matters as even a minimal increase in the partial pressure of oxygen is efficient in triggering cellular reactions by eliciting the production of hypoxia-inducible factors and heat-shock proteins. Moreover, it was shown that extreme environments could also interact with the genome; in fact, epigenetics appears to play a major role in extreme environments and exercise, especially when changes in oxygen partial pressure are involved. Hyperbaric oxygen therapy is, essentially, "intermittent oxygen" exposure. We must investigate hyperbaric oxygen with a new paradigm of treating oxygen as a potent stimulus of the molecular network of reactions.

Critical Flicker Fusion Frequency: A Narrative Review.

This review presents the current knowledge of the usage of critical flicker fusion frequency (CFF) in human and animal model studies. CFF has a wide application in different fields, especially as an indicator of cortical arousal and visual processing. In medicine, CFF may be helpful for diagnostic purposes, for example in epilepsy or minimal hepatic encephalopathy. Given the environmental studies and a limited number of other methods, it is applicable in diving and hyperbaric medicine. Current research also shows the relationship between CFF and other electrophysiological methods, such as electroencephalography. The human eye can detect flicker at 50-90 Hz but reports are showing the possibility to distinguish between steady and modulated light up to 500 Hz. Future research with the use of CFF is needed to better understand its utility and application.

Spinal cord decompression sickness in an inside attendant after a standard hyperbaric oxygen treatment session.

Medical personnel in hyperbaric treatment centres are at occupational risk for decompression sickness (DCS) while attending patients inside the multiplace hyperbaric chamber (MHC). A 51-year-old male hyperbaric physician, also an experienced diver, was working as an inside attendant during a standard hyperbaric oxygen therapy (HBOT) session (70 minutes at 253.3 kPa [2.5 atmospheres absolute, 15 metres' seawater equivalent]) in a large walk-in MHC. Within 10 minutes after the end of the session, symptoms of spinal DCS occurred. Recompression started within 90 minutes with an infusion of lignocaine and hydration. All neurological symptoms resolved within 10 minutes breathing 100% oxygen at 283.6 kPa (2.8 atmospheres absolute) and a standard US Navy Treatment Table 6 was completed. He returned to regular hyperbaric work after four weeks of avoiding hyperbaric exposures. Transoesophageal echocardiography with a bubble study was performed 18 months after the event without any sign of a persistent (patent) foramen ovale. Any hyperbaric exposure, even within no-decompression limits, is an essential occupational risk for decompression sickness in internal hyperbaric attendants, especially considering the additional risk factors typical for medical personnel (age, dehydration, tiredness, non-optimal physical capabilities and frequent problems with the lower back).

Coupling between Blood Pressure and Subarachnoid Space Width Oscillations during Slow Breathing.

The precise mechanisms connecting the cardiovascular system and the cerebrospinal fluid (CSF) are not well understood in detail. This paper investigates the couplings between the cardiac and respiratory components, as extracted from blood pressure (BP) signals and oscillations of the subarachnoid space width (SAS), collected during slow ventilation and ventilation against inspiration resistance. The experiment was performed on a group of 20 healthy volunteers (12 females and 8 males; BMI=22.1±3.2 kg/m2; age 25.3±7.9 years). We analysed the recorded signals with a wavelet transform. For the first time, a method based on dynamical Bayesian inference was used to detect the effective phase connectivity and the underlying coupling functions between the SAS and BP signals. There are several new findings. Slow breathing with or without resistance increases the strength of the coupling between the respiratory and cardiac components of both measured signals. We also observed increases in the strength of the coupling between the respiratory component of the BP and the cardiac component of the SAS and vice versa. Slow breathing synchronises the SAS oscillations, between the brain hemispheres. It also diminishes the similarity of the coupling between all analysed pairs of oscillators, while inspiratory resistance partially reverses this phenomenon. BP-SAS and SAS-BP interactions may reflect changes in the overall biomechanical characteristics of the brain.

High-Altitude Decompression Sickness Treated with Hyperbaric Therapy and Extracorporeal Oxygenation.

BACKGROUND: High-altitude decompression sickness (HADCS) is a rare condition that has been associated with aircraft accidents. To the best of our knowledge, the present paper is the first case report of a patient treated for severe HADCS using recompression therapy and veno-venous extracorporeal oxygenation (VV-ECMO) with a complete recovery.CASE REPORT: After depressurization of a cabin, the 51-yr-old jet pilot was admitted to the Military Institute of Medicine with a life-threatening HADCS approximately 6 h after landing from a high-altitude flight, in a dynamically deteriorating condition, with progressing dyspnea and edema, reporting increasing limb paresthesia, fluctuating consciousness, and right-sided paresis. Hyperbaric oxygen therapy in the intensive care mode was initiated. A therapeutic recompression with U.S. Navy Treatment Table 6 was performed with neurological improvement. Due to cardiovascular collapse, sedation, mechanical ventilation, and significant doses of catecholamines were started, followed by continuous veno-venous hemodialysis. In the face of disturbances in oxygenation, during the second day of treatment the patient was commenced on veno-venous extracorporeal oxygenation. Over the next 6 d, the patient's condition slowly improved. On day 7, VV-ECMO was discontinued. On day 19, the patient was discharged with no neurological deficits.DISCUSSION: We observed two distinct stages during the acute phase of the disease. During the first stage, signs of hypoperfusion, neurological symptoms, and marbled skin were observed. During the second stage, multiple organ dysfunction dominated, including heart failure, pulmonary edema, acute kidney injury, and fluid overload, all of which can be attributed to extensive endothelial damage.Siewiera J, Szalanski P, Tomaszewski D, Kot J. High-altitude decompression sickness treated with hyperbaric therapy and extracorporeal oxygenation. Aerosp Med Hum Perform. 2020; 91(2):106-109.

The Hyperbaric Protective Tube: A housing for a left ventricular assist device (LVAD) in a multiplace hyperbaric chamber.

INTRODUCTION: During a hyperbaric oxygen therapy (HBOT) session, every medical device that is used within the hyperbaric chamber is exposed to several hazards, including an increased ambient pressure and partial pressure of oxygen. In Europe, all medical devices marketed and/or sold for use in hyperbaric conditions must be tested by the manufacturer and marked 'CE' if approved. At the moment, no left ventricular assist device (LVAD) has been formally approved and CE-marked for HBOT. CASE: A 65-year-old male was referred to our Hyperbaric Centre for HBOT due to a persistent life-threating soft tissue infection of the non-removable wire connecting the external controller with the pump implanted into the left ventricle of the heart (Heartware LVAD). The aim of the intervention reported here was to safely conduct HBOT sessions with this non-CE marked medical device. After risk analysis, the decision was made to isolate the external part of the LVAD (controller and batteries) from the ambient conditions in the hyperbaric chamber by placing it in a pressure-resistant housing that was vented to the external atmosphere. The housing, a 'Hyperbaric Protective Tube' was built and tested, and the resulting operating procedures were practiced by personnel involved in the patient's care. Thirty uneventful HBOT standard sessions were conducted with subsequent clinical improvement of the soft tissue infection, resulting in an extended timeframe for awaiting heart transplantation. CONCLUSION: An isolation housing that vents into the dumping system of the hyperbaric chamber allows for the safe use of critical medical devices without prior testing for their compatibility with the hyperbaric environment.

Diving physiopathology: the end of certainties? Food for thought.

Our understanding of decompression physiopathology has slowly improved during this last decade and some uncertainties have disappeared. A better understanding of anatomy and functional aspects of patent foramen ovale (PFO) have slowly resulted in a more liberal approach toward the medical fitness to dive for those bearing a PFO. Circulating vascular gas emboli (VGE) are considered the key actors in development of decompression sickness and can be considered as markers of decompression stress indicating induction of pathophysiological processes not necessarily leading to occurrence of disease symptoms. During the last decade, it has appeared possible to influence post-dive VGE by a so-called "preconditioning" as a pre-dive denitrogenation, exercise or some pharmacological agents. In the text we have deeply examined all the scientific evidence about this complicated but challenging theme. Finally, the role of the "normobaric oxygen paradox" has been clarified and it is not surprising that it could be involved in neuroprotection and cardioprotection. However, the best level of inspired oxygen and the exact time frame to achieve optimal effect is still not known. The aim of this paper was to reflect upon the most actual uncertainties and distil out of them a coherent, balanced advice towards the researchers involved in gas-bubbles-related pathologies.