Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.

In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47-0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.

Functional MRI evaluation of hyperbaric oxygen therapy effect on hand motor recovery in a chronic post-stroke patient: a case report and physiological discussion.

Introduction: Impairments in activities of daily living (ADL) are a major concern in post-stroke rehabilitation. Upper-limb motor impairments, specifically, have been correlated with low quality of life. In the current case report, we used both task-based and resting state functional MRI (fMRI) tools to investigate the neural response mechanisms and functional reorganization underlying hyperbaric oxygen therapy (HBOT)-induced motor rehabilitation in a chronic post-stroke patient suffering from severe upper-limb motor impairment. Methods: We studied motor task fMRI activation and resting-state functional connectivity (rsFC) in a 61-year-old right-handed male patient who suffered hemiparesis and physical weakness in the right upper limb, 2 years after his acute insult, pre- and post-treatment of 60 daily HBOT sessions. Motor functions were assessed at baseline and at the end of the treatment using the Fugl-Meyer assessment (FMA) and the handgrip maximum voluntary contraction (MVC). Results: Following HBOT, the FMA score improved from 17 (severe impairment) to 31 (moderate impairment). Following the intervention during trials involving the affected hand, there was an observed increase in fMRI activation in both the supplementary motor cortex (SMA) and the premotor cortex (PMA) bilaterally. The lateralization index (LI) decreased from 1 to 0.63, demonstrating the recruitment of the contralesional hemisphere. The region of interest, ROI-to-ROI, analysis revealed increased post-intervention inter-hemispheric connectivity (P = 0.002) and a between-network connectivity increase (z-score: 0.35 ± 0.21 to 0.41 ± 0.21, P < 0.0001). Seed-to-voxel-based rsFC analysis using the right SMA as seed showed increased connectivity to the left posterior parietal cortex, the left primary somatosensory cortex, and the premotor cortex. Conclusion: This study provides additional insights into HBOT-induced brain plasticity and functional improvement in chronic post-stroke patients.

Hyperbaric oxygen therapy compared to pharmacological intervention in fibromyalgia patients following traumatic brain injury: A randomized, controlled trial.

Fibromyalgia is a chronic pain syndrome with unsatisfactory response to current treatments. Physical trauma, including traumatic brain Injury (TBI) is among the etiological triggers. Hyperbaric Oxygen therapy (HBOT) is an intervention that combines 100% oxygen with elevated atmospheric pressure. HBOT has been applied as a neuro-modulatory treatment in central nervous system-related conditions. The current study investigated the utility of HBOT for TBI-related fibromyalgia. Fibromyalgia patients with a history of TBI were randomized to either HBOT or pharmacological intervention. HBOT protocol comprised 60 daily sessions, breathing 100% oxygen by mask at 2 absolute atmospheres (ATA) for 90 minutes. Pharmacological treatment included Pregabalin or Duloxetine. The primary outcome was subjective pain intensity on visual analogue scale (VAS); Secondary endpoints included questionnaires assessing fibromyalgia symptoms as well as Tc-99m-ECD SPECT brain imaging. Pain threshold and conditioned pain modulation (CPM) were also assessed. Results demonstrated a significant group-by-time interaction in pain intensity post-HBOT compared to the medication group (p = 0.001), with a large net effect size (d = -0.95) in pain intensity reduction following HBOT compared to medications. Fibromyalgia related symptoms and pain questionnaires demonstrated significant improvements induced by HBOT as well as improvements in quality of life and increase in pain thresholds and CPM. SPECT demonstrated significant group-by-time interactions between HBOT and medication groups in the left frontal and the right temporal cortex. In conclusion, HBOT can improve pain symptoms, quality of life, emotional and social function of patients suffering from FMS triggered by TBI. The beneficial clinical effect is correlated with increased brain activity in frontal and parietal regions, associated with executive function and emotional processing.

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial.

INTRODUCTION: Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. METHODS: In this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n = 37) or sham treatment (n = 36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. RESULTS: The ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p < 0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F = 7.81, P = 0.007). The efficacy measure had significant group-by-time interactions (F = 5.98, p = 0.017) in the amygdala circuit. CONCLUSIONS: This study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.

Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial.

Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8-15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = - 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Persistent post-concussive syndrome in children after mild traumatic brain injury is prevalent and vastly underdiagnosed.

Data on epidemiology and prognosticators of persistent post-concussion syndrome (PPCS) after mild traumatic brain injury (mTBI) in the pediatric population is scarce. The aim of this study was to evaluate the prevalence of PPCS in children after mTBI and to identify clinical variables in children who are at high risk for developing PPCS. A multicenter, retrospective matched cohort in which PPCS symptoms were evaluated in children 8-15-year-old, 6-60 months after being admitted to the emergency department because of mTBI. The control group included children admitted to the emergency department because of uncomplicated distal radius fractures. The children's guardians were interviewed for the presence of PPCS symptoms using the "Rivermead Post-Concussion Questionnaire". A multivariable logistic regression model was used to identify predictors of PPCS. Two-hundred and five children were included in the mTBI group and 205 in the control. The median time from the injury was 33.5 months in the mTBI group and 33.8 in the control. The prevalence of PPCS in the mTBI group was 25.3% and PPCS like symptoms in the control was 2.4%, p < 0.001. Within the 6-60 months period, the PPCS prevalence was not influenced by the time that elapsed from the injury. In the mTBI group, motor vehicle accidents and adolescence were found to be risk factors for PPCS. PPCS is underdiagnosed in the pediatric population and 25% of children admitted to the ED due to mTBI may suffer from PPCS. Screening guidelines should be implemented to identify and properly treat these children.

Effects of Hyperbaric Oxygen Therapy on Mitochondrial Respiration and Physical Performance in Middle-Aged Athletes: A Blinded, Randomized Controlled Trial.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) has been used to increase endurance performance but has yet to be evaluated in placebo-controlled clinical trials. The current study aimed to evaluate the effect of an intermittent HBOT protocol on maximal physical performance and mitochondrial function in middle-aged master athletes. METHODS: A double-blind, randomized, placebo-controlled study on 37 healthy middle-aged (40-50) master athletes was performed between 2018 and 2020. The subjects were exposed to 40 repeated sessions of either HBOT [two absolute atmospheres (ATA), breathing 100% oxygen for 1 h] or SHAM (1.02ATA, breathing air for 1 h). RESULTS: Out of 37 athletes, 16 HBOT and 15 SHAM allocated athletes were included in the final analysis. Following HBOT, there was a significant increase in the maximal oxygen consumption (VO2Max) (p = 0.010, effect size(es) = 0.989) and in the oxygen consumption measured at the anaerobic threshold (VO2AT)(es = 0.837) compared to the SHAM group. Following HBOT, there were significant increases in both maximal oxygen phosphorylation capacity (es = 1.085, p = 0.04), maximal uncoupled capacity (es = 0.956, p = 0.02) and mitochondrial mass marker MTG (p = 0.0002) compared to the SHAM sessions. CONCLUSION: HBOT enhances physical performance in healthy middle-age master athletes, including VO2max, power and VO2AT. The mechanisms may be related to significant improvements in mitochondrial respiration and increased mitochondrial mass. Trial Registration ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT03524989 (May 15, 2018).

Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: A prospective, randomized, controlled trial.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is characterized by changes in both brain activity and microstructural integrity. Cumulative evidence demonstrates that hyperbaric oxygen therapy (HBOT) induces neuroplasticity and case-series studies indicate its potentially positive effects on PTSD. The aim of the study was to evaluate HBOT's effect in veterans with treatment resistant PTSD. METHODS: Veterans with treatment resistant PTSD were 1:1 randomized to HBOT or control groups. All other brain pathologies served as exclusion criteria. Outcome measures included clinician-administered PTSD scale-V (CAPS-V) questionnaires, brief symptom inventory (BSI), BECK depression inventory (BDI), brain microstructural integrity evaluated by MRI diffuse tensor imaging sequence (DTI), and brain function was evaluated by an n-back task using functional MRI (fMRI). The treatment group underwent sixty daily hyperbaric sessions. No interventions were performed in the control group. RESULTS: Thirty-five veterans were randomized to HBOT (N = 18) or control (n = 17) and 29 completed the protocol. Following HBOT, there was a significant improvement in CAPS-V scores and no change in the control (F = 30.57, P<0.0001, Net effect size = 1.64). Significant improvements were also demonstrated in BSI and BDI scores (F = 5.72, P = 0.024 Net effect size = 0.89, and F = 7.65, P = 0.01, Net effect size = 1.03). Improved brain activity was seen in fMRI in the left dorsolateral prefrontal, middle temporal gyri, both thalami, left hippocampus and left insula. The DTI showed significant increases in fractional anisotropy in the fronto-limbic white-matter, genu of the corpus callosum and fornix. CONCLUSIONS: HBOT improved symptoms, brain microstructure and functionality in veterans with treatment resistant PTSD.

The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial.

INTRODUCTION: Skin biopsies can be used to evaluate physiological effects of aging targeted intervention at the tissue/cellular levels. Recent clinical trials have shown that hyperbaric oxygen therapy (HBOT) can target aging hallmarks, including telomere shortening, senescent cells clearance and angiogenesis. The aim of this study was to evaluate the effects of HBOT on the skin of a normal, non-pathological, aging population. METHODS: The study was performed as a prospective clinical trial. After signing informed consent and undergoing baseline evaluations, the subjects were assigned to a three-month control period followed by three months of HBOT daily sessions. Skin biopsies were taken at baseline, after three months of no intervention (control) and 1-2 weeks following the last HBOT session. Trichrome, Orecin, lipofuscin and CD31 staining were used to evaluate collagen fibers, elastic fibers, senescent cells and blood vessels, respectively. RESULTS: Out of the cohort of 70 participants in the normal aging population study, thirteen male patients (age 68.07±2.5y) gave consent for repeated skin biopsies. Following HBOT, there was a significant increase in collagen density (p<0.001, effect size(es)=1.10), elastic fiber length (p<0.0001, es=2.71) and the number of blood vessels (p=0.02, es=1.00). There was a significant decrease in fiber fragmentation (p=0.012) and in tissue senescent cells (p=0.03, es=0.84) post-HBOT. No changes were noted in elastic fiber density or thickness. CONCLUSIONS: The study indicates, for the first time in humans, that HBOT can significantly modulate the pathophysiology of the skin aging in a healthy aging population. The demonstrated mechanisms include angiogenesis and senescent cell clearance.

Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. Changes in gene expression can alter activity in defined age-related molecular pathways leading to cellular aging and increased aging disease susceptibility. The aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects gene expression in normal, non-pathological, aging adults. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th HBOT session, and 1-2 weeks following the last session. Differential gene expression analysis was performed. RESULTS: Following 60 sessions of HBOT, 1342 genes and 570 genes were differently up- and downregulated (1912 total), respectively (p < 0.01 FDR), compared to baseline. Out of which, five genes were downregulated with a >1.5-fold change: ABCA13 (FC = -2.28), DNAJ6 (FC = -2.16), HBG2 (FC = -1.56), PDXDC1 (FC = -1.53), RANBP17 (FC = -1.75). Two weeks post-HBOT, ABCA13 expression was significantly downregulated with a >1.5fold change (FC = -1.54, p = 0.008). In conclusion, for the first time in humans, the study provides direct evidence of HBOT is associated with transcriptome changes in whole-blood samples. Our results demonstrate significant changes in gene expression of normal aging population.

Safety and humoral responses to BNT162b2 mRNA vaccination of SARS-CoV-2 previously infected and naive populations.

Since COVID-19 risk of reinfection is of great concern, the safety and efficacy of the mRNA-based vaccines in previously infected populations should be assessed. We studied 78 individuals previously infected with SARS-CoV-19, who received a single dose of BNT162b2 mRNA COVID-19 vaccine, and 1:2 ratio matched infection-naïve cohort who received two injections. The evaluation procedure included symptom monitoring, and serological tests. Among the post-infected population, the median IgG-S response after the first vaccine dose was 3.35 AU, compared to 2.38 AU after the second vaccine injection in the infection naive group. A strong correlation was demonstrated between IgG-S level before vaccination, and the corresponding responses after a single vaccine dose (r = 0.8, p < 0.001) in the post infected population. Short-term severe symptoms that required medical attention were found in 6.8% among the post-infected individuals, while none were found in the infection naïve population. Our data suggest that a single vaccine dose is sufficient to induce an intense immune response in post-infected population regardless of seropositivity. Although some short-term safety issues were observed compared to the infection naïve population, a single dose regimen can be considered safe in post-infected populations.

Early and long term antibody kinetics of asymptomatic and mild disease COVID-19 patients.

Most patients infected with SARS-CoV-2 are asymptomatic or mildly symptomatic. However, the early and late antibody kinetics, and the association between antibody levels, clinical symptoms, and disease phase in these patients have not yet been fully defined. Confirmed SARS-CoV-2 patients and their household contacts were evaluated over a period four months. The evaluation procedure included symptom monitoring, viral load and serology analysis every ten days. A total of 1334 serum samples were collected from 135 patients and analyzed using three assays for IgG-N, IgG-S and IgM antibodies. Of the study participants, 97% were seropositive during the study, and two distinct clusters were identified. These clusters were significantly different in their inflammatory related symptoms. Peak IgG-S was 40.0 AU/ml for the non-inflammatory cluster and 71.5 AU/ml for the inflammatory cluster (P = 0.006), whereas IgG-N peaks were 4.3 and 5.87 (P = 0.023) respectively. Finally, a decision tree model was designed to predict the disease phase based on the serological titer levels, and had an overall accuracy of 80.7%. The specific profile of seroconversion and decay of serum antibodies can be used to predict the time-course from the acute infection.

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. RESULTS: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals.

Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a "sham" treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice.

Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.

More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.

Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis.

BACKGROUND: Previous studies have shown that hyperbaric oxygen therapy (HBOT) can improve the motor functions and memory of post-stroke patients in the chronic stage. OBJECTIVE: The aim of this study is to evaluate the effects of HBOT on overall cognitive functions of post-stroke patients in the chronic stage. The nature, type and location of the stroke were investigated as possible modifiers. METHODS: A retrospective analysis was conducted on patients who were treated with HBOT for chronic stroke (>3 months) between 2008-2018. Participants were treated in a multi-place hyperbaric chamber with the following protocols: 40 to 60 daily sessions, 5 days per week, each session included 90 min of 100% oxygen at 2 ATA with 5 min air brakes every 20 minutes. Clinically significant improvements (CSI) were defined as > 0.5 standard deviation (SD). RESULTS: The study included 162 patients (75.3% males) with a mean age of 60.75±12.91. Of them, 77(47.53%) had cortical strokes, 87(53.7%) strokes were located in the left hemisphere and 121 suffered ischemic strokes (74.6%).HBOT induced a significant increase in all the cognitive function domains (p < 0.05), with 86% of the stroke victims achieving CSI. There were no significant differences post-HBOT of cortical strokes compared to sub-cortical strokes (p > 0.05). Hemorrhagic strokes had a significantly higher improvement in information processing speed post-HBOT (p < 0.05). Left hemisphere strokes had a higher increase in the motor domain (p < 0.05). In all cognitive domains, the baseline cognitive function was a significant predictor of CSI (p < 0.05), while stroke type, location and side were not significant predictors. CONCLUSIONS: HBOT induces significant improvements in all cognitive domains even in the late chronic stage. The selection of post-stroke patients for HBOT should be based on functional analysis and baseline cognitive scores rather than the stroke type, location or side of lesion.

Hyperbaric Oxygen Therapy Can Induce Neuroplasticity and Significant Clinical Improvement in Patients Suffering From Fibromyalgia With a History of Childhood Sexual Abuse-Randomized Controlled Trial.

Background: Fibromyalgia syndrome (FMS), a condition considered to represent a prototype of central sensitization syndrome, can be induced by different triggers including childhood sexual abuse (CSA). Recent studies have demonstrated hyperbaric oxygen therapy (HBOT) can induce neuroplasticity and improve clinical outcome of FMS. The aim of the current study was to evaluate the effect of HBOT on patients suffering from FMS with a history of CSA. Materials and methods: A prospective randomized clinical trial conducted between July 2015 and November 2017 included women with a history of CSA who fulfilled fibromyalgia diagnosis criteria for at least 5 years prior to inclusion. Included participants (N = 30) were randomly assigned to treatment group, treated with 60 HBOT sessions and a control/crossover group received psychotherapy. After the control period, the control/crossover group was crossed to HBOT. Clinical outcomes were assessed using FMS questioners, post-traumatic stress disorder (PTSD) questioners and quality of life questioners. Objective outcome were assessed using brain function and structure imaging. Findings: Following HBOT, there was a significant improvement in all FMS questionnaires (widespread pain index, Fibromyalgia symptoms severity scale, Fibromyalgia functional impairment), most domains of quality of life, PTSD symptoms and psychological distress. The same significant improvements were demonstrated in the control following crossover to HBOT. Following HBOT, brain SPECT imaging demonstrated significant increase in brain activity in the prefrontal cortex, orbital frontal cortex, and subgenual area (p < 0.05). Brain microstructure improvement was seen by MRI-DTI in the anterior thalamic radiation (p = 0.0001), left Insula (p = 0.001), and the right Thalamus (p = 0.001). Conclusion: HBOT induced significant clinical improvement that correlates with improved brain functionality and brain microstructure in CSA related FMS patients. Trial Registration: www.Clinicaltrials.gov, identifier: NCT03376269. url: https://clinicaltrials.gov/show/NCT03376269.

Effect of Peripheral Electrical Stimulation (PES) on Nocturnal Blood Glucose in Type 2 Diabetes: A Randomized Crossover Pilot Study.

BACKGROUND: Regulation of hepatic glucose production has been a target for antidiabetic drug development, due to its major contribution to glucose homeostasis. Previous pre-clinical study demonstrated that peripheral electrical stimulation (PES) may stimulate glucose utilization and improve hepatic insulin sensitivity. The aim of the present study was to evaluate safety, tolerability, and the glucose-lowering effect of this approach in patients with type 2 diabetes (T2DM). METHODS: Twelve patients with T2DM were recruited for an open label, interventional, randomized trial. Eleven patients underwent, in a crossover design, an active, and a no-intervention control periods, separated with a two-week washout phase. During the active period, the patients received a daily lower extremity PES treatment (1.33Hz/16Hz burst mode), for 14 days. Study endpoints included changes in glucose levels, number of hypoglycemic episodes, and other potential side effects. Endpoints were analyzed based on continuous glucose meter readings, and laboratory evaluation. RESULTS: We found that during the active period, the most significant effect was on nocturnal glucose control (P < 0.0004), as well as on pre-meal mean glucose levels (P < 0.02). The mean daily glucose levels were also decreased although it did not reach clinical significance (P = 0.07). A reduction in serum cortisol (P < 0.01) but not in insulin was also detected after 2 weeks of treatment. No adverse events were recorded. CONCLUSIONS: These results indicate that repeated PES treatment, even for a very short duration, can improve blood glucose control, possibly by suppressing hepatic glucose production. This effect may be mediated via hypothalamic-pituitary-adrenal axis modulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02727790.