Immediate and Long-Term Effects of Hyperbaric Oxygenation in Patients with Long COVID-19 Syndrome Using SF-36 Survey and VAS Score: A Clinical Pilot Study.

(1) Background: Long COVID syndrome (LCS) is a heterogeneous long-standing condition following COVID-19 infection. Treatment options are limited to symptomatic measures, and no specific medication has been established. Hyperbaric oxygenation (HBO) has been found to have a positive impact on the treatment of COVID-19 infection. This study evaluates both the feasibility and outcome of supportive HBO in patients with LCS. (2) Methods: Within 17 months, 70 patients with proven LCS were prospectively included. Each patient underwent a cycle of 10 subsequent HBO treatment sessions administered for 75 min at 2.2 atmospheres. Evaluation of the patients was performed before the first and after the last HBO session and 3 months afterwards. Statistical evaluation was based on an intention-to-treat analysis using Fisher's exact test and Student's t-test for paired samples. (3) Results: In total, 59 patients (33 females, 26 males; mean age: 43.9 years; range: 23-74 years; median: 45.0) were evaluable. After HBO, a statistically significant improvement of physical functioning (p < 0.001), physical role (p = 0.01), energy (p < 0.001), emotional well-being (p < 0.001), social functioning (p < 0.001), pain (p = 0.01) and reduced limitation of activities (p < 0.001) was confirmed. (4) Conclusions: Physical functioning and both the physical and emotional role improved significantly and sustainably, suggesting HBO as a promising supportive therapeutic tool for the treatment of LCS.

Survey of Molecular Mechanisms of Hyperbaric Oxygen in Tissue Repair.

For more than six decades, hyperbaric oxygen (HBO) has been used for a variety of indications involving tissue repair. These indications comprise a wide range of diseases ranging from intoxications to ischemia-reperfusion injury, crush syndrome, central nervous injury, radiation-induced tissue damage, burn injury and chronic wounds. In a systematic review, the molecular mechanisms triggered by HBO described within the last two decades were compiled. They cover a wide range of pathways, including transcription, cell-to-cell contacts, structure, adhesion and transmigration, vascular signaling and response to oxidative stress, apoptosis, autophagy and cell death, as well as inflammatory processes. By analyzing 71 predominantly experimental publications, we established an overview of the current concepts regarding the molecular mechanisms underlying the effects of HBO. We considered both the abovementioned pathways and their role in various applications and indications.

The History and Development of Hyperbaric Oxygenation (HBO) in Thermal Burn Injury.

Background and Objectives: Hyperbaric oxygenation (HBO) denotes breathing of 100% oxygen under elevated ambient pressure. Since the initiation of HBO for burns in 1965, abundant experimental and clinical work has been done. Despite many undisputedly positive and only a few controversial results on the efficacy of adjunctive HBO for burn injury, the method has not yet been established in clinical routine. Materials and Methods: We did a retrospective analysis of the literature according to PRISMA-guidelines, from the very beginning of HBO for burns up to present, trying to elucidate the question why HBO is still sidelined in the treatment of burn injury. Results: Forty-seven publications (32 animal experiments, four trials in human volunteers and 11 clinical studies) fulfilled the inclusion criteria. Except four investigators who found little or no beneficial action, all were able to demonstrate positive effects of HBO, most of them describing less edema, improved healing, less infection or bacterial growth and most recently, reduction of post-burn pain. Secondary enlargement of burn was prevented, as microvascular perfusion could be preserved, and cells were kept viable. The application of HBO, however, concerning pressure, duration, frequency and number of treatment sessions, varied considerably. Authors of large clinical studies underscored the intricate measures required when administering HBO in severe burns. Conclusions: HBO unquestionably has a positive impact on the pathophysiological mechanisms, and hence on the healing and course of burns. The few negative results are most likely due to peculiarities in the administration of HBO and possibly also to interactions when delivering the treatment to severely ill patients. Well-designed studies are needed to definitively assess its clinical value as an adjunctive treatment focusing on relevant outcome criteria such as wound healing time, complications, length of hospital stay, mortality and scar quality, while also defining optimal HBO dosage and timing.

Application of Hyperbaric Oxygen Reduce Oxidative Damage of Plasmatic Carbonyl Proteins and 8-OHdG by Activating Glutathion Peroxidase.

BACKGROUND: It is postulated that application of hyperbaric oxygenation may induce the production of radicals after HBO. Higher oxygenation and transport of oxygen increase the mitochondrial energy turnover, whereas inner mitochondrial radical formation decreases. METHODS: Several markers of oxidative stress in healthy volunteers (n = 21), including plasma carbonyl proteins (CP), malondialdehyde (MDA), oxidized LDL (oxLDL), 8-hydroxy-deoxyguanosine (8-OHdG), and erythrocyte glutathione peroxidase (GPx) activity are measured before, during, and after HBO. RESULTS: Median plasma concentrations of CP decreased significantly during HBO compared to CP levels before HBO (from 77.1 to 61.7 pmol/mg; p < 0.001) and increased again after HBO (to 78.1 pmol/mg; p = 0.035). 8-OHdG decreased significantly during HBO (8.1 ng/mL; p < 0.001) and remained constant after HBO (8.1 ng/mL) compared to "before HBO" (9.4 ng/mL). MDA increased significantly from 0.92 µM (before HBO) to 1.26 µM (during HBO, p < 0.01) and decreased again to 1.00 µM (after HBO, p = 0.023). Erythrocyte GPx activity also increased significantly during HBO (26.5 ± 14.7; p = 0.005), but not after HBO (25.6 ± 17.2 IU/mg). A negative correlation was observed between GPx and MDA only during HBO (r = -0.518; p = 0.016). CONCLUSIONS: We assume that higher oxygen consumption decreases, on the one hand, the inner mitochondrial generation of free radicals and, on the other, RONS by activation of detoxifying enzymes like GPx.

Vitamin D and cancer mortality: systematic review of prospective epidemiological studies.

Accumulating evidence from experimental and epidemiological studies suggests that vitamin D deficiency might be a causal risk factor for cancer and therewith associated mortality. We performed a systematic review in Medline up to February 2012 to identify prospective studies on 25-hydroxyvitamin D (25[OH]D) and cancer mortality as well as on 25(OH)D and survival in cancer patients. Our search retrieved 13 studies on cancer-specific mortality and 20 studies on overall mortality in cancer patients. Data on 25(OH)D and cancer mortality were mainly derived from general populations. The results were inconsistent and yielded either no, inverse or positive associations. By contrast, the majority of studies in cancer patients showed that patients with higher 25(OH)D levels had a decreased risk of mortality. This relationship was particularly evident in cohorts of colorectal cancer patients. In contrast, there was no indication for increased mortality risk with higher vitamin D levels in any cancer cohort. In conclusion, the relationship of vitamin D status and cancerspecific mortality is still unclear and warrants further studies. Our results provide a strong rationale to perform prospective randomized controlled studies to document a potential effect of vitamin D supplementation on survival in cancer patients.

The impact of preoperative micronutrient supplementation in lung surgery. A prospective randomized trial of oral supplementation of combined alpha-ketoglutaric acid and 5-hydroxymethylfurfural.

OBJECTIVE: Preoperative micronutrient supplementation in fast-track surgery programs have shown to reduce complications, shorten recovery, and thereby lower costs. In a prospective randomized study, the metabolic effects of a combination of alpha-ketoglutaric acid (alpha-KG) and 5-hydroxymethylfurfural (5-HMF) were evaluated concerning their impact on improvement of exercise capacity and reduction of oxidative stress in lung surgery. METHODS: Thirty-two consecutive patients admitted for lung resection due to NSCLC were randomized to the study protocol. All patients received preoperative nutritional guidelines according to general recommendations. In 16 (study group), a supplementation of 7.2g alpha-KG and 720 mg 5-HMF/day (SANOPAL) was administered from days 1 to 10. Spiroergometric evaluation was carried out at baseline and day 10 after micronutrient supplementation. Blood samples for the determination of oxidative stress, i.e. carbonyl proteins (CPs) and isoprostanes (IPs) were taken on at baseline, in the operating room just before resection treatment, and 25 min after single lung ventilation (SLV). RESULTS: Spiroergometric re-evaluation showed a significant increase of VO2max (p=0.0108) and Watt's (p=0.011) in favor of the study group. Determination of oxidative stress showed a significant reduction of CPs before (p=0.048) and after SLV (p=0.0001) for the study group compared to the control group. The same is true for IPs before (p=0.003) and after SLV (p=0.02). Hospitalization and intensive care unit (ICU) of the study group showed a significant reduction compared to the control group (p=0.03 and p=0.02, respectively). CONCLUSIONS: Simple oral supplementation using a combination of alpha-KG and 5-HMF of preoperative micronutrition may therefore be one further step in a multimodality approach of fast-track surgery programs also in lung surgery.