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) [...].

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.

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 [...].

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.

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.

Coupling of Blood Pressure and Subarachnoid Space Oscillations at Cardiac Frequency Evoked by Handgrip and Cold Tests: A Bispectral Analysis.

The aim of the study was to assess blood pressure-subarachnoid space (BP-SAS) width coupling properties using time-frequency bispectral analysis based on wavelet transforms during handgrip and cold tests. The experiments were performed on a group of 16 healthy subjects (F/M; 7/9) of the mean age 27.2 ± 6.8 years and body mass index of 23.8 ± 4.1 kg/m2. The sequence of challenges was first handgrip and then cold test. The handgrip challenge consisted of a 2-min strain, indicated by oral communication from the investigator, at 30% of maximum strength. The cold test consisted of 2 min of hand immersion to approximately wrist level in cold water of 4 °C, verified by a digital thermometer. Each test was preceded by 10 min at baseline and was followed by 10-min recovery recordings. BP and SAS were recorded simultaneously. Three 2-min stages of the procedure, baseline, test, and recovery, were analyzed. We found that BP-SAS coupling was present only at cardiac frequency, while at respiratory frequency both oscillators were uncoupled. Handgrip and cold test failed to affect BP-SAS cardiac-respiratory coupling. We showed similar handgrip and cold test cardiac bispectral coupling for individual subjects. Further studies are required to establish whether the observed intersubject variability concerning the BP-SAS coupling at cardiac frequency has any potential clinical predictive value.

Consensus guideline: Pre-hospital management of decompression illness: expert review of key principles and controversies.

(Mitchell SJ, Bennett MH, Bryson P, Butler FK, Doolette DJ, Holm JR, Kot J, Lafère P. Pre-hospital management of decompression illness: expert review of key principles and controversies. Diving and Hyperbaric Medicine. 2018 March;48(1):45е.doi.10.28920/dhm48.1.45-55.) Guidelines for the pre-hospital management of decompression illness (DCI) had not been formally revised since the 2004 Divers Alert Network/Undersea and Hyperbaric Medical Society workshop held in Sydney, entitled "Management of mild or marginal decompression illness in remote locations." A contemporary review was initiated by the Divers Alert Network and undertaken by a multinational committee with members from Australasia, the USA and Europe. The process began with literature reviews by designated committee members on: the diagnosis of DCI; first aid strategies for DCI; remote triage of possible DCI victims by diving medicine experts; evacuation of DCI victims; effect of delay to recompression in DCI; pitfalls in management when DCI victims present at hospitals without diving medicine expertise and in-water recompression. This was followed by presentation of those reviews at a dedicated workshop at the 2017 UHMS Annual Scientific Meeting, discussion by registrants at that workshop and, finally, several committee meetings to formulate statements addressing points considered of prime importance to the management of DCI in the field. The committee placed particular emphasis on resolving controversies around the definition of "mild DCI" arising over 12 years of practical application of the 2004 workshop's findings, and on the controversial issue of in-water recompression. The guideline statements are promulgated in this paper. The full workshop proceedings are in preparation for publication.

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.

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.

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.

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).

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.

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.

Prognostic significance of HER2 expression in neuroblastic tumors.

HER2 is essential for normal embryonic development and has a critical function in oncogenesis and progression of some types of cancer. Neuroblastic tumors create a heterogenous group of pediatric embryonal tumors of sympathoadrenal lineage. The biological and prognostic function of HER2 in these tumors is not well established. In this study, we evaluated the status of HER2, its prognostic significance, and clinicopathological correlations in series of 79 untreated neuroblastoma. The immunohistochemical assessment of HER2 and Ki-67 (proliferation index) as well as HER2 copy number status were performed on tissue microarrays. HER2 expression characterized 63 tumors, including 34 with low and 29 with high level, showing either membranous or mixed membranous-cytoplasmic pattern. Sixteen cases were HER2 immunonegative. The pattern of immunolabeling depended on the maturity of neuroblastic cells, being the most intense in differentiating neuroblasts. None of the tumors revealed HER2 amplification. In the examined group, 20% of patients died of disease from 4 to 107 months (median 18) from the diagnosis, and the survivors were followed up for 14-149 months (median 59). Patients' age, stage of disease, tumor location, mitosis/karyorrhexis index (MKI), and presence of HER2 expression were statistically significantly related to survival probability as detected by the Cox proportional hazard model. In the univariate analysis, Kaplan-Meier curves revealed significantly poorer outcome of HER2 negative than HER2-positive tumors (either low or high expression). The immunonegativity was associated with adverse clinicopathological parameters, including poor survival, metastatic stage of disease, un- or poorly differentiated histology, high MKI, and higher proliferation index. In conclusion, HER2 expression, not accompanied by gene amplification, is common in neuroblastic tumors. HER2 positivity seems to have a positive prognostic significance. HER2 expression with a variable pattern is a marker of the stage of neuroblastic cells differentiation.

Isoprostanes-biomarkers of lipid peroxidation: their utility in evaluating oxidative stress and analysis.

Isoprostanes (IsoPs) are key biomarkers for investigating the role of free radical generation in the pathogenesis of human disorders. To solve IsoPs-related problems with regard to isoprostanes, analytical tools are required. This paper reviews the problems and trends in this field focusing on the methodology for assaying biomarkers in exhaled breath condensate (EBC) samples. A large amount of work has been done in the qualitative and quantitative analysis of IsoPs, but a standardized method has yet to emerge. The methodologies described differ, either in the sample preparation steps or in the detection techniques, or both. Requiring a number of chromatographic steps, the relevant extraction and purification procedures are often critical and time-consuming, and they lead to a substantial loss of target compounds. Recent data show that EBC is a promising non-invasive tool for the evaluation of different diseases. Two main analytical approaches have been adopted for IsoPs measurement: immunological methods and mass spectrometry. The methodologies for the extraction, purification and analysis of IsoPs in EBC samples are presented.