Letter to the Editor
The New Vision of Transformative Medical Research via NIH to Make America Healthy Again (MAHA) [1] involves four priorities: 1) Preventing, reversing, and treating iatrogenic illnesses 2) Addressing the country’s mental health crisis 3) Combating diabetes and metabolic disorders and 4) Mitigating the rise of autoimmune diseases. While research is a necessity, its timeline precludes implementation of results in the narrow 2–4-year window of the New Vision. Effective treatment of the illnesses in #’s 1-4 could have a rapid impact and the only therapy that has both stand-alone and adjunctive potential to achieve this is hyperbaric therapy/hyperbaric oxygen therapy.
Hyperbaric therapy (HT)/hyperbaric oxygen therapy (HBOT) is a 362-year-old therapy [2] that has been applied to over 132 conditions [3]. It is a treatment for common acute and chronic wound pathophysiology [4-7] found in acute and chronic wound [4-9] and inflammatory conditions [4-12]. Composed of increased barometric pressure and hyperoxia [13] it takes advantage of all living organisms’ sensitivity to changes in environmental pressure [14] and oxygen. When delivered intermittently HT/HBOT exploits this natural phenomenon to have wide-ranging effects on disease pathophysiology [4].
The core effect of HBOT is its epigenetic DNA signaling capability [15] that became understood in 2009 and 2010. In two experiments, HBOT demonstrated independent, overlapping, and interactive effects of increased barometric pressure and increased pressure of oxygen [16] on 8,101 of the 19,000 (40.3%) protein-coding genes embedded in our 46 human chromosomes [17]. The largest clusters of genes turned on were the anti-inflammatory genes and the growth/repair hormone genes, while the largest clusters of temporarily suppressed genes were the pro-inflammatory genes and the genes coding for programmed cell death. These two experiments explained 346 years of application to wounding and inflammatory conditions by showing inhibition of inflammation, stimulation of tissue growth/repair in damaged areas, and cessation of programmed cell death with every exposure to increased barometric pressure and increased oxygen (a hyperbaric treatment).
These two discoveries can impact the four cornerstones of the New Vision as follows:
- Preventing, reversing, and treating iatrogenic illnesses: HBOT’s effects on mitigating iatrogenic illnesses are partially dependent upon predicting the iatrogenic illnesses. In the case of medication errors and other unpredictable medical errors, pre-error administration of HBOT is impossible. In those cases, many of which result in “wounding” conditions characterized by the inflammatory process, an extensive literature documents the beneficial effects of HBOT on treatment of hypoxic/ischemic reperfusion injury (RI)[18-25], particularly the white blood cell mediated component [19-23] RI is the inflammatory injury pathophysiology when interrupted blood flow is re-established, but also occurs after nearly every insult to the human body that involves wounding/tissue injury due to hypoxia, ischemia, mechanical, chemical, or electric insults. First identified in the signature diagnosis of the hyperbaric medicine specialty, decompression illness [20], HBOT treats the cerebral RI from bubble passage through the brain blood vessels, not the treatment of bubbles themselves [20]. It is the dominant effect of HBOT in six of the fifteen typically reimbursed indications for HBOT in the U.S. today: decompression sickness, air embolism, carbon monoxide poisoning, compromised flaps and grafts, acute arterial insufficiency, and thermal burns [4]. It is a generic effect [24] that would impact many emergency conditions and iatrogenic diseases that involve tissue injury or interruption of blood supply, particularly when applied immediately after the iatrogenic error [25,26].
For known, expected, and predictable iatrogenic harm, HBOT can mitigate RI before the iatrogenic insult is delivered. Now known as pre-conditioning this was first demonstrated in acute carbon monoxide poisoning [22] where a single pre-carbon monoxide HBOT exposure mitigated the severity of RI. For mild stresses/insults/injuries, considered as hormetic stresses [27], HBOT pre-conditioning is not a mandate. Such stresses alone may generate beneficial effects as embodied by Friedrich Nietzsche’s principle [28], “What doesn’t kill you makes you stronger.” If an ischemic, hypoxic, mechanical, or other stress/insult/injury exceeds this hormetic level, one to five HBOTs prior to the insult pre-conditions the organism/human to experience less damage from the insult [29]. This has been demonstrated in reversible models of ischemia/reperfusion injury and now in an extensive literature on the subject [30].
Alex, et al. [31] utilized two pre-conditioning HBOTs the night before cardiac bypass surgery to significantly decrease cognitive injury. Applied to both higher risk and healthy patients before any operation that involves planned interruption of blood supple [e.g., arterial bypass surgeries, cardiac bypass surgeries, extremity tourniquet procedures (vascular or orthopedic), organ transplantation, etc.], urgent/emergent procedures with interruption of blood supply (e.g., traumatic repair of limbs, re-attachment of severed parts, flap and graft procedures, crush injuries, severe traumatic injuries, etc.) or substantial risk of blood loss/hypotension, HBOT has the potential to and can mitigate the effects of trauma, surgical injury, and surgical complication [32]. - Addressing the country’s mental health crisis: HBOT’s benefit to mental health is best understood in the context of the biological model of psychiatry [33]. If psychiatric diseases result from organic disturbances of the brain and some of these disturbances are considered to be due to stress/insults/wounding conditions, they are potentially responsive to HBOT. This is suggested in mild TBI HBOT studies where depression and/or anxiety were reduced [34-38]. In the same studies HBOT achieved significant PTSD symptom relief. A systematic review concluded, “In multiple randomized and randomized controlled clinical trials HBOT demonstrated statistically significant symptomatic improvements, Reliable Changes, or Clinically Significant Changes in patients with PTSD symptoms or PTSD over a wide range of pressure and oxygen doses,” using the U.S. Veterans Affairs grading system for PTSD [39]. Based on imaging findings, the study concluded that PTSD could no longer be considered strictly a psychiatric disease. The application of HBOT to Americans with PTSD could immediately impact the mental health crisis in America, particularly for our veterans who are in the midst of a suicide epidemic.
A greater immediate impact of HBOT could be achieved with another “psychiatric” disorder, persistent post-concussion syndrome [40]. Despite inarguable evidence of physical damage to the brain in mild TBI, particularly to the white matter [41-49], but also gray matter [43-45,50,51], persistent post-concussion syndrome is defined as a psychiatric condition [40]. A systematic review concluded that HBOT for mTBI PPCS was Level I evidence and a Grade A Practice Recommendation [52]. Preceding this literature, three randomized trials from the 1970s to 2013 have shown that HBOT reduces the mortality in acute severe TBI by 50% [53-55]. While these studies should have changed the standard of care, this application awaits the results of the current multi-center trial of HBOT in acute severe TBI [56]. - Combating diabetes and metabolic disorders: HBOT has demonstrated significant benefit in the most common hospital admission diagnosis for diabetics, diabetic foot wounds. Diabetic foot wounds often lead to major lower limb amputations which are associated with a 3-year mortality of 64-71% [57]. In multiple controlled trials, HBOT has demonstrated wound healing and reduction in major amputations [58]. The latter effect was the basis for the application to CMS in 11/2001 and the decision by CMS to reimburse HBOT treatment of diabetic foot ulcers (DFUs) [59]. Unfortunately, the population that has benefited the least from this indication is the veteran population. Between 2002-2022, less than 6.36% of veterans undergoing lower limb amputation for diabetic foot ulcers received HBOT [57]. If applied according to CMS rules, HBOT could have an immediate impact on the health of our veteran population with DFUs.
- Mitigating the rise of autoimmune diseases: Mitigating the rise of autoimmune disease requires identifying and reducing/eliminating the causes of autoimmune disease which are likely the lifelong environmental chemical and toxin exposures to/ingestions by humans. Eliminating these causes involves a concerted environmental, industrial, corporate, agricultural, government, and individual personal effort that will take years to achieve. In the meantime, HBOT can mitigate autoimmune and immune system disorders characterized by chronic focal or systemic inflammation. In gene experiments (vide supra), HBOT has demonstrated wide-ranging effects on immunomodulatory genes in normal non-diseased cells [60-62] and on inflammation in autoimmune and inflammatory disorders [63-68]. Given the contribution of inflammation to 8 of the top 10 leading causes of death in the U.S.[69], HBOT has the potential to treat a long list of diseases and contribute to The New Vision.
Important inflammatory diseases in which HBOT could make a significant contribution to the New Vision are acute severe COVID infection and Post-COVID Syndrome. Unbeknownst to the current generation of doctors, HBOT’s introduction to the United States occurred during the Spanish Flu Pandemic when HBOT was successfully delivered to moribund dying Spanish Flu patients [2,70]. The HBOT benefit was due to treatment of the intense inflammatory components of Spanish Flu. A similar responsiveness to acute COVID-19 infection was first demonstrated in Wuhan [71,72], subsequently replicated by others [73], and extended to patients with Post-COVID Syndrome [74,75] and brain fog [76]. A recent study showed that over 55% of Americans with prior COVID infection have 3 or more persistent symptoms at least one month after COVID 19 infection [77]. With no acknowledged effective treatment options, HBOT could significantly impact the health of these patients and contribute to the New Vision. - Additional consideration of importance–HBOT application to chronic neurological disorders: Many neurological disorders, e.g., TBI (vide supra), birth injury/asphyxia, and cerebral palsy, share the same pathogenesis and pathophysiology as the traditional HBOT-treated wounding and inflammatory conditions. Application of one HBOT in 1963 to neonates who were born not breathing and failed resuscitation resulted in resuscitation and discharge “apparently well” of 54% of the infants [78]. HBOT’s treatment of reperfusion injury was likely the determining factor. Subsequent studies [79,80] have supported this 1963 study and argue for the treatment of apneic newborns.
For chronic pediatric brain injury, specifically cerebral palsy, the evidence is even more compelling [81,82,83]. A comparative effectiveness study of all traditional therapies found HBOT to be four times as effective as the average effect of all other therapies on motor function in CP children [84]. In addition, the HBOT studies demonstrated significant improvement in other functional domains, including cognition. These studies and the ones on birth injury indicate that HBOT could have an impact on acute and chronic pediatric neurological disease and contribute to the New Vision.
In summary, hyperbaric oxygen therapy is a dual-component therapy consisting of increased pressure and increased pressure of oxygen that takes advantage of all living organisms’ sensitivity to pressure and oxygen. It has epigenetic effects on normal tissue and diseases, namely, growth of tissue, inhibition of inflammation, inhibition of cell death, and healing of wounds. Because of these effects, scientific studies have demonstrated HBOT benefit in a wide range of human diseases, only a fraction of which are currently treated with this therapy. Based on the science, application to these diseases and more can immediately impact the four cornerstones of the New Vision to Make America Healthy Again.
Acknowledgments
Funding: Protected time as academic faculty, Louisiana State University Health Sciences Center.
Conflict of Interest: Paul G. Harch, M.D. is the owner of Harch Hyperbarics, Inc. an S-Corporation, that is the vehicle for his private practice of hyperbaric medicine.
References
1
Lyons-Weiler J. A New Vision of Transformative Medical Research via NIH to Make America Healthy Again. Popular Rationalism, 11/12/2024: https://popularrationalism.substack.com/p/a-new-vision-of-transformative-medical (last accessed 12-8-2024).
2
Trimble VH. The Uncertain Miracle, Hyperbaric Oxygenation. Garden City, New York: Doubleday and Company; 1974.
3
Gabb G, Robin ED. Hyperbaric oxygen, a therapy in search of diseases. Chest. 1987;92:1074–82. doi: 10.1378/chest.92.6.1074 https://doi.org/10.1378/chest.92.6.1074
4
Huang ET, ed. Hyperbaric Medicine Indications Manual, 15th ed. North Palm Beach, FL: Best Publishing Company; 2023.
5
Harch PG. Textbook of hyperbaric medicine. 6th Revised Edition; Jain KK, editor. Cham, Switzerland: Springer; 2017. Chapter 20, HBO therapy in global cerebral ischemia/anoxia and coma; p. 269–319
6
National Coverage Determination (NCD) hyperbaric oxygen therapy (20.29). Centers for Medicare and Medicaid Services. National Coverage Determinations (NCD) manual; 2017. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.Aspx (Accessed September 11, 2021).
7
Jain KK. Textbook of hyperbaric medicine. 6th Revised Edition; Jain KK, editor. Cham, Switzerland: Springer; 2017. Chapter 49, Worldwide overview of hyperbaric medicine; p. 609–14.
8
Takahashi H, Yagi H. Textbook of hyperbaric medicine, 5th Revised Edition; Jain KK, editor. Gottingen: Hogrefe and Huber Publishers; 2009. Chapter 42, Hyperbaric medicine in Japan; p. 495–8.
9
Mathieu D, Marroni A, Kot J. Consensus conference: tenth European consensus conference on hyperbaric medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med. 2017;47:24–32. doi: 10.28920/dhm47.2.131-132. https://doi.org/10.28920/dhm47.2.131-132
10
Ortega MA, Fraile-Martinez O, García-Montero C, Callejón-Peláez E, Sáez MA, Álvarez-Mon MA, et al. A general overview on the hyperbaric oxygen therapy: applications, mechanisms and translational opportunities. Medicine (Kaunas). 2021;57:864. doi: 10.3390/medicina57090864 https://doi.org/10.3390/medicina57090864
11
Wahl AM, Bidstrup D, Smidt-Nielsen IG, Werner MU, Hyldegaard O, Rotball-Nielsen PR. A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: a replicated, randomized controlled clinical trial. J Pain Res. 2019;12:2337–48. doi: 10.2147/JPR.S198359 https://doi.org/10.2147/JPR.S198359
12
Hasan B, Yirn Y, Rashid MU, Khalid RA, Sarvepalli D, Castaneda D, et al. Hyperbaric oxygen therapy in chronic inflammatory conditions of the pouch. Inflamm Bowel Dis. 2021;15:965–70. doi: 10.1093/ibd/izaa245 https://doi.org/10.1093/ibd/izaa245
13
Harch PG. New scientific definitions: hyperbaric therapy and hyperbaric oxygen therapy. Med Gas Res. 2023;13(2):92-93.
14
Macdonald AG, Fraser PJ. The transduction of very small hydrostatic pressures. Comp Biochem Physiol A Mol Integr Physiol. 1999;122:13-36.
15
Siddiqui A, Davidson JD, Mustoe TA. Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy: a new physiologic concept. Plast Reconstr Surg. 1997;99:148-155.
16
Chen Y, Nadi NS, Chavko M, Auker CR, McCarron RM. Microarray analysis of gene expression in rat cortical neurons exposed to hyperbaric air and oxygen. Neurochem Res. 2009;34:1047-1056.
17
Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones. 2010;15:431-442.
18
PubMed Search: Hyperbaric oxygen AND reperfusion injury [Internet]. Available from: https://pubmed-ncbi-nlm-nih-gov.lsuhscno.idm.oclc.org/?term=hyperbaric+oxygen+AND+reperfusion+injury. Last accessed 11/29/2024.
19
Francis A, Baynosa R. Ischaemia-reperfusion injury and hyperbaric oxygen pathways: a review of cellular mechanisms. Diving Hyperb Med. 2017;47(2):110-117.
20
Harch PG. Treatment of Decompression Illness, 45th Workshop of the Undersea and Hyperbaric Medical Society; Moon RE, Sheffield PJ, editors. Kensington, MD: Undersea and Hyperbaric Medical Society; 1996. Late treatment of decompression illness and use SPECT brain imaging; p. 203–42.
21
Zamboni WA, Roth AC, Russell RC, Graham B, Suchy H, Kucan JO. Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. Plast Reconstr Surg. 1993;91(6):1110–23.
22
Thom SR. Functional inhibition of leukocyte B 2 integrins by hyperbaric oxygen in carbon monoxide- mediated brain injury in rats. Toxicol Appl Pharmacol. 1993;123:248–56.
23
Haapaniemi T. Hyperbaric oxygen reduces ischemia-induced skeletal muscle injury. Plast Reconstr Surg. 1996;97(3): Zamboni WA, Roth AC, Russell RC, Graham B, Suchy H, Kucan JO. Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. Plast Reconstr Surg. 1993;91(6):1110–23. 602-607.
24
Harch PG. Generic inhibitory drug effect of hyperbaric oxygen therapy (HBOT) on reperfusion injury (RI). Eur J Neurol. 2000;7(3):150. Abstract #:FW8-2.
25
Van Meter K, Sheps S, Kriedt F, Moises J, Barratt D, Murphy-Lavoie H, Harch PG, Bazan N. Hyperbaric oxygen improves rate of return of spontaneous circulation after prolonged normothermic porcine cardiopulmonary arrest. Resuscitation. 2008;78(2):200-214.
26
Van Meter K, Harch PG. Textbook of Hyperbaric Medicine, 5th Revised Edition; Jain KK, editor. Seattle, WA: Hogrefe and Huber Publishers; 2009. Chapter 39, HBO in Emergency Medicine; p. 453-482.
27
Kouda K, Iki M. Beneficial effects of mild stress (hormetic effects): dietary restriction and health. J Physiol Anthropol. 2010;29(4):127-32.
28
Nietzsche F. Gotzen-Dammerung (Twilight of the Idols or How to Philosophize with a Hammer)–Aphorism #8. Original publication: 1869, Leipzig. Translator (English) R.J. Hollingdale. Penquin Classics. 1990. ISBN 978-0140445145.
29
Gao ZX, Rao J, Li YH. Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation. Neural Regen Res. 2017;12(2):329-336.
30
Pubmed Search: Hyperbaric oxygen preconditioning [Internet]: available from: https://pubmed-ncbi-nlm-nih-gov.lsuhscno.idm.oclc.org/?term=hyperbaric+oxygen+preconditioning. Last accessed 11-29-2024.
31
Alex J, Laden G, Cale AR, Bennett S, Flowers K, Madden L, Gardiner E, McCollum PT, Griffin SC. Pretreatment with hyperbaric oxygen and its effect on neuropsychometric dysfunction and systemic inflammatory response after cardiopulmonary bypass: a prospective randomized double-blind trial. J Thorac Cardiovasc Surg. 2005;130:1623-1630.
32
Boet S, Martin L, Cheng-Boivin O, Etherington C, Louge P, Pignel R, et al. Can preventive hyperbaric oxygen therapy optimize surgical outcome? Eur J Anaesthesiol. 2020;37:636-648.
33
Deacon BJ. The biomedical model of mental disorder: a critical analysis of its validity, utility, and effects on psychotherapy research. Clin Psychol Rev. 2013;33(7):846-61. doi: 10.1016/j.cpr.2012.09.007. https://doi.org/10.1016/j.cpr.2012.09.007
34
Wolf G, Cifu DX, Baugh L, Carne W, Profenna L. The effect of hyperbaric oxygen on symptoms following mild traumatic brain injury. J Neurotrauma. 2012;29:2606–12. doi: 10.1089/neu.2012.2549 https://doi.org/10.1089/neu.2012.2549
35
Harch PG, Andrews SR, Fogarty EF, Lucarini J, Van Meter KW. Case control study: hyperbaric oxygen treatment of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder. Med Gas Res. 2017;7(3):156-174.
36
Harch PG, Andrews SR, Rowe CJ, Lischka JR, Townsend MH, Yu Q, Mercante DE. Hyperbaric oxygen therapy for mild traumatic brain injury persistent postconcussion syndrome: a randomized controlled trial. Med Gas Res. 2020;10(1):8-20.
37
Miller RS, Weaver LK, Bahraini N, Churchill S, Price RC, Skiba V, et al. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent Postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. 2015;175:43–52. doi: 10.1001/jamainternmed.2014.5479. https://doi.org/10.1001/jamainternmed.2014.5479
38
Weaver IK, Wilson SH, Lindblad AS, Churchill S, Deru K, Price RC, et al. Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial. Undersea Hyperb Med. 2018;45:129–56. doi: 10.22462/03.04.2018.1. https://doi.org/10.22462/03.04.2018.1
39
Andrews SR and Harch PG (2024) Systematic review and dosage analysis: hyperbaric oxygen therapy efficacy in the treatment of posttraumatic stress disorder. Front Neurol. 15:1360311. doi: 10.3389/fneur.2024.1360311. https://doi.org/10.3389/fneur.2024.1360311
40
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed., text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000. Appendix B, Criteria Sets and Axes Provided for Further Study. p. 759-762.
41
Oppenheimer DR. Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiat. 1968;31:299–306. doi: 10.1136/jnnp.31.4.299. https://doi.org/10.1136/jnnp.31.4.299
42
Wallace EJ, Mathias JL, Ward L. Diffusion tensor imaging changes following mild, moderate and severe adult traumatic brain injury: a meta-analysis. Brain Imaging Behav. 2018;12:1607–21. doi: 10.1007/s11682-018-9823-2. https://doi.org/10.1007/s11682-018-9823-2
43
Shively SB, Horkayne-Szakaly I, Jones RV, Kelly JP, Armstrong RC, Perl DP. Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series. Lancet Neurol. 2016;15:944–53. doi: 10.1016/S1474-4422(16)3 0057-6. https://doi.org/10.1016/S1474-4422(16)3%200057-6
44
Povlishock JT. Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol. 1992;2:1–12.
45
Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB, et al. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics. Cell Mol Neurobiol. 2017;37:571–85. doi: 10.1007/s10571-016-0400-1. https://doi.org/10.1007/s10571-016-0400-1
46
Povlishock JT, Becker DP, Cheng CLY, Vaughan GW. Axonal change in minor head injury. J Neuropath Exper Neurol. 1983;42:225–42. doi: 10.1097/00005072-198305000-00002. https://doi.org/10.1097/00005072-198305000-00002
47
Kimura H, Meaney DF, McGowan JC, Grossman RI, Lenkinski RE, Ross DT, et al. Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation. J Comput Assist Tomogr. 1996;20:540–6. doi: 10.1097/00004728-199607000-00007. https://doi.org/10.1097/00004728-199607000-00007
48
Bauman RA, Ling G, Tong L, Januszkiewicz A, Agoston D, Delanerolle N, et al. An introductory characterization of a combat-casualty-care relevant swine model of closed head injury resulting from exposure to explosive blast. J Neurotrauma. 2009;26:841–60. doi: 10.1089/neu.2008.0898. https://doi.org/10.1089/neu.2008.0898
49
Agamanolis DP. Chapter 4, Traumatic brain injury and increased intracranial pressure [Internet]. In: Neuropathology, an Illustrated Interactive Course for Medical Students and Residents. Rootstown, OH: Northeast Ohio Medical University (2017). Available from: https://neuropathology-web.org/chapter4/chapter4bContusions_dai_sbs.html (accessed December 12, 2024).
50
Ryu J, Horkayne-Szakaly I, Xu L, Pletnikova O, Leri F, Eberhart C, et al. The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathol Commun. 2014;2:153. doi: 10.1186/s40478-014-0153-3. https://doi.org/10.1186/s40478-014-0153-3
51
Roth TL, Nayak D, Atanasijevic T, Koretsky AP, Latour LL, McGavern DB. Transcranial amelioration of inflammation and cell death after brain injury. Nature. 2014;505:223–35. doi: 10.1038/nature12808. https://doi.org/10.1038/nature12808
52
Harch PG. Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome. Front. Neurol. 2022;13:815056. doi: 10.3389/fneur.2022.815056. https://doi.org/10.3389/fneur.2022.815056
53
Holbach KH, Wassmann H, Kolberg T. Verbesserte Reversibilität des Traumatischen Mittelhirnsyndromes bei Anwendung der Hyperbaren Oxygenierung. (Improved reversibility of the traumatic midbrain syndrome following the use of hyperbaric oxygenation. Acta Neurochir. 1974;30:247–56. doi: 10.1007/BF01405583. https://doi.org/10.1007/BF01405583
54
Rockswold GL, Ford SE, Anderson DC, Bergman TA, Sherman RF. Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. J Neurosurg. 1992;76:929–34. doi: 10.3171/jns.1992.76.6.0929. https://doi.org/10.3171/jns.1992.76.6.0929
55
Rockswold SB, Rockswold GL, Zaun DA, Liu J, A. prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg. 2013;118:1317–28. doi: 10.3171/2013.2.JNS121468. https://doi.org/10.3171/2013.2.JNS121468
56
Rockswold GL. Multi-center trial of HBOT in acute severe TBI [Internet]. Available from: https://nett.umich.edu/sites/default/files/docs/hobit_protocol.pdf.
57
Koleda EW. The Veteran Diabetic Foot Ulcer (DFU) Epidemic: A U.S. Department of Veterans Health Administration (VHA) Hyperbaric Oxygen Therapy (HBOT) Services Review. Available from: TreatNow.org, 10/25/2022: https://treatnow.org/hundreds-of-thousands-of-veterans-are-dying/.
58
Sharma, R., Sharma, S.K., Mudgal, S.K. et al. Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Sci Rep. 2021;11:2189. doi: 10.1038/s41598-021-81886-1. CMS decision memo HBOT in Diabetic Foot Wounds. https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=37&keyword=hyperbaric%20oxygen%20therapy&keywordType=starts&areaId=all&docType=NCA,CAL,NCD,MEDCAC,TA,MCD,6,3,5,1,F,P&contractOption=all&sortBy=relevance&bc=1. https://doi.org/10.1038/s41598-021-81886-1
59
Centers for Medicare and Medicaid Services. National Coverage Analysis (NCA), Decision Memo. Hyperbaric Oxygen Therapy for Hypoxic Wounds and Diabetic Wounds of the Lower Extremities. CAG-00060N. 8/30/2002. Available at: https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=37&keywordtype=starts&keyword=hyperbaric&bc=0.
60
Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones. 2010;15:431-442.
61
Chen Y, Nadi NS, Chavko M, Auker CR, McCarron RM. Microarray analysis of gene expression in rat cortical neurons exposed to hyperbaric air and oxygen. Neurochem Res. 2009;34:1047-1056.
62
Kendall AC, Whatmore JL, Harries LW, Winyard PG, Eggle-ton P, Smerdon GR. Different oxygen treatment pressures alter inflammatory gene expression in human endothelial cells. Undersea Hyperb Med. 2013;40:115-123.
63
Paganini M, Bosco G, Perozzo FAG, Kohlscheen E, Sonda R, Bassetto F, et al. The role of hyperbaric oxygen treatment for COVID-19: a review. Adv Exp Med Biol – Clinical and Experimental Biomedicine. 2021;11: 27–35 DOI 10.1007/5584_2020_568. https://doi.org/10.1007/5584_2020_568
64
Feldmeier JJ, Kiorby JP, Buckey JC. Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen. Undersea Hyperb Med. 2021;48(1):1-12.
65
Wu X, Liang TY, Wang Z, Chen G. The role of hyperbaric oxygen therapy in inflammatory bowel disease: a narrative review. Med Gas Res. 2021;11(2):66-71.
66
Rossignol DA, Bradstreet JJ, Van Dyke K, Schneider C, Freedenfeld SH, O’Hara N, et al. Hyperbaric oxygen treatment in autism spectrum disorders. Medical Gas Research. 2012;2:16.
67
Kjellbert A, De Maio A, Lindholm P. Can hyperbaric oxygen safely serve as an anti-inflammatory treatment for COVID-19? Med Hypoth. 2020;144:110224. doi: 10.1016/j.mehy.2020.110224. https://doi.org/10.1016/j.mehy.2020.110224
68
Al-Waili, N.S. and Butler, G.J. (2006) Effects of hyperbaric oxygen on inflammatory response to wound and trauma: possible mechanism of action. The Scientific World Jouenl. 2006;6:425–441. DOI 10.1100/tsw.2006.78. https://doi.org/10.1100/tsw.2006.78
69
Slavich GM. Understanding inflammation, its regulation, and relevance for health: A top scientific and public priority. Brain Behav Immun. 2015;45:13-14. doi:10.1016/j.bbi.2014.10.012. https://doi.org/10.1016/j.bbi.2014.10.012
70
Sellers LM. The fallibility of the forrestian principle. “semper pri-mus pervenio maxima cum VI”. Laryngoscope. 1964;74:613-633.
71
Chen R.-Y., Tang Y.-C., Zhong X.-L., Liang Y., Li B.-J., Tao X.-L., Liao C.-B. Efficacy analysis of hyperbaric oxygen therapy in the treatment of severe coronavirus disease 2019 patients. Acad J Second Mil Med Univ. 2020;6:604–611.
72
Zhong X.T.Y., Chen R. Effect of Hyperbaric Oxygen Therapy on HBOT in Patients with Severe New Coronavirus Pneumonia: First Report Chinese. Chin J Naut Med Hyperb Med. 2020;27:132–135. doi: 10.3760/cma.j.cn311847-20200220-00059. https://doi.org/10.3760/cma.j.cn311847-20200220-00059
73
Allam NM, Eladl HM, Eid MM. Hyperbaric oxygen therapy as a supportive therapy for COVID-19 patients: a narrative review. Eur Rev Med Pharmacol Sci. 2022;26(15):5618-5623. doi: 10.26355/eurrev_202208_29435. PMID: 35993661. https://doi.org/10.26355/eurrev_202208_29435
74
Basharat S, Spry C. Hyperbaric Oxygen Therapy: An Emerging Therapy for Post–COVID-19 Condition: CADTH Horizon Scan [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2023 Aug. Report No.: EN0050. PMID: 37934848.
75
Wu, B.-Q.; Liu, D.-Y.; Shen, T.-C.; Lai, Y.-R.; Yu, T.-L.; Hsu, H.-L.; Lee, H.-M.; Liao, W.-C.; Hsia, T.-C. Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review. Life. 2024;14:438. doi: 10.3390/life14040438. https://doi.org/10.3390/life14040438
76
Gorenshtein A, Liba T, Leibovitch L, Stern S, Stern Y. Intervention modalities for brain fog caused by long-COVID: systematic review of the literature. Neurol Sci. 2024;45(7):2951-2968. doi: 10.1007/s10072-024-07566-w. Epub 2024 May 2. PMID: 38695969; PMCID: PMC11176231. https://doi.org/10.1007/s10072-024-07566-w
77
Swank Z, Borberg E, Chen Y, Senussi Y, Chalise S, Manickas-Hill Z, Yu XG, Li JZ, Alter G, Henrich TJ, Kelly JD, Hoh R, Goldberg SA, Deeks SG, Martin JN, Peluso MJ, Talla A, Li X, Skene P, Bumol TF, Torgerson TR, Czartoski JL, McElrath MJ, Karlson EW, Walt DR; RECOVER consortium authors. Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study. Clin Microbiol Infect. 2024;30(12):1599-1605. doi: 10.1016/j.cmi.2024.09.001. Epub 2024 Oct 9. PMID: 39389851; PMCID: PMC11578795. https://doi.org/10.1016/j.cmi.2024.09.001
78
Hutchison JH, Kerr MM, Williams KG, Hopkinson WI. Hyperbaric oxygen in the resuscitation of the newborn. Lancet. 1963 Nov;2(7316):1019-22. doi: 10.1016/s0140-6736(63)90001-1. PMID: 14062718. https://doi.org/10.1016/s0140-6736(63)90001-1
79
Mielecki D, Godlewski J and Salinska E. Hyperbaric oxygen therapy for the treatment of hypoxic/ischemic injury upon perinatal asphyxia—are we there yet? Front Neurol. 2024;15:1386695. doi: 10.3389/fneur.2024.1386695. https://doi.org/10.3389/fneur.2024.1386695
80
Sánchez-Rodríguez EC and López VJ. Hypoxic ischemic encephalopathy (HIE). Front Neurol. 2024;15:1389703. doi: 10.3389/fneur.2024.1389703. https://doi.org/10.3389/fneur.2024.1389703
81
McDonagh M, Carson S, Ash J, et al. Hyperbaric Oxygen Therapy for Brain Injury, Cerebral Palsy, and Stroke. Evidence Report/Technology Assessment No. 85. Roockville, MD: Agency for Healthcare Research and Quality (US); September, 2003. AHRQ Publication No. 03-E050.
82
Harch PG, Gottlieb SF, Van Meter KW, Staab P. HMPAO SPECT brain imaging and low pressure HBOT in the diagnosis and treatment of chronic traumatic, ischemic, hypoxic and anoxic encephalopathies. Undersea Hyperb Med. 1994;21(Suppl):30.
83
Harch PG. Textbook of Hyperbaric Medicine, 6th Revised Edition; Cham, Switzerland: Springer; 2017. Chapter 23, HBO in the Management of Cerebral Palsy; p. 351-364.
84
Marois P, Letellier G, Marois M and Ballaz L. Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy – could it end the controversy? Front Neurol. 2024;15:1347361. doi: 10.3389/fneur.2024.1347361. https://doi.org/10.3389/fneur.2024.1347361