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Abstract Background Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. Methods This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression. Results The final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values. Conclusions This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. Trial registration The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

Background: Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. Methods: This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression. Results: The final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values. Conclusions: This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. Trial registration: The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024. [ABSTRACT FROM AUTHOR]

Background: Stroke, including ischemic and hemorrhagic stroke, is a severe and prevalent acute cerebrovascular disease. The development of hypoxia following stroke can trigger a cascade of pathological events, including mitochondrial dysfunction, energy deficiency, oxidative stress, neuroinflammation, and excitotoxicity, all of which are often associated with unfavorable prognosis. Nonetheless, a noninvasive intervention, referred to as normobaric hyperoxia (NBO), is known to have neuroprotective effects against stroke. Results: NBO can exert neuroprotective effects through various mechanisms, such as the rescue of hypoxic tissues, preservation of the blood–brain barrier, reduction of brain edema, alleviation of neuroinflammation, improvement of mitochondrial function, mitigation of oxidative stress, reduction of excitotoxicity, and inhibition of apoptosis. These mechanisms may help improve the prognosis of stroke patients. Conclusions: This review summarizes the mechanism by which hypoxia causes brain injury and how NBO can act as a neuroprotective therapy to treat stroke. We conclude that NBO has significant potential for treating stroke and may represent a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Normobaric hyperoxia (NBO) is a potentially promising stroke treatment strategy that could protect the ischemic penumbra and could be administered as an adjunct before vascular recanalization. However, the efficacy and safety of NBO have not been confirmed by randomized controlled trials. The study aims to assess the efficacy and safety of NBO for ischemic stroke due to large artery occlusion (LVO) of acute anterior circulation among patients who had endovascular treatment (EVT) and were randomized within 6 h from symptom onset. Based on the data of the modified Rankin Scale (mRS) score at 90 days from the normobaric hyperoxia combined with EVT for acute ischemic stroke (OPENS: NCT03620370) trial, 284 patients will be included to achieve a 90% power by using Wilcoxon-Mann-Whitney test and the proportional odds model to calculate the sample size. The study is a prospective, multicenter, blinded, randomized controlled trial. The NBO group is administered with mask oxygen therapy of 10 L/min, while the sham NBO group is with that of 1 L/min. The primary outcome is the mRS score at 90 days. Secondary endpoints include cerebral infarct volume at 24–48 h, functional independence (mRS ≤2) at 90 days, and improvement in neurological function at 24 h. Safety outcomes include 90-day mortality, oxygen-related adverse events, and serious adverse events. This study will indicate whether NBO combined with EVT is superior to EVT alone for acute ischemic stroke caused by LVO in subjects randomized within 6 h from symptom onset and will provide some evidence for NBO intervention as an adjunct to thrombectomy for acute stroke. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH‐mediated brain damage, but the underlying mechanism still remains elusive. Aims: In the present study, we investigated the effects of complement C3 on NBO‐treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH‐mediated brain injury. Results: Hemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic‐induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia‐mediated synaptic pruning. Conclusions: Our results revealed that NBO exerts its neuroprotective effects by reducing C3‐mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke. Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed. Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO. Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety.

Acute ischemic stroke (AIS) is a serious neurological disease. Normobaric hyperoxia (NBHO) is both a non-invasive and easy method that seems to be able to improve outcomes after cerebral ischemia/reperfusion. In clinical trials, normal low-flow oxygen has been shown to be ineffective, but NBHO has been shown to have a transient brain-protective effect. Today, NBHO combined with recanalization is the best treatment available. NBHO combined with thrombolysis is considered to improve neurological scores and long-term outcomes. Large randomized controlled trials (RCTs), however, are still needed to determine the role they will have in stroke treatment. RCTs of NBHO combined with thrombectomy have both improved infarct volume at 24 hours and the long-term prognosis. These two mechanisms most likely play key roles in the neuroprotective actions of NBHO after recanalization, including the increase in penumbra oxygen supply and the integrity of the blood-brain barrier (BBB). Considering the mechanism of action of NBHO, oxygen should be given as early as possible to increase the duration of oxygen therapy before recanalization is initiated. NBHO can further prolong the existence time of penumbra, so that more patients may benefit from it. Overall, however, recanalization therapy is still essential. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to deter- mine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Acute cerebral ischemia is caused by an insufficient blood supply to brain tissue. Oxygen therapy, which is able to aid diffusion to reach the ischemic region, has been regarded as a possible treatment for cerebral ischemia. Recent animal and pilot clinical studies have reported that normobaric hyperoxia (NBO) showed neuroprotective effects if started soon after the onset of stroke. However, little is known about the role and mechanism of NBO treatment in astrocytes. Connexin43, one of the main gap junction proteins in astrocytes, is extremely sensitive to hypoxia and oxidative stress after cerebral ischemia. Aims: In the present study, we used sutures to develop an ischemia/reperfusion model in rats to mimic clinical recanalization and investigated the role of connexin43 in NBO‐treated stroke rats, as well as the underlying mechanism of NBO therapy. Results: Normobaric hyperoxia treatment maintained the homeostasis of oxidoreductases: glutathione peroxidase 4 (GPX4) and NADPH oxidase 4 (two important oxidoreductases) and rescued the ischemia/reperfusion‐induced downregulation of connexin43 protein in astrocytes. Furthermore, NBO treatment attenuated cerebral ischemia‐induced cytochrome c release from mitochondria and was involved in neuroprotective effects by regulating the GPX4 and connexin43 pathway, using Ferrostatin‐1 (an activator of GPX4) or Gap27 (an inhibitor of connexin43). Conclusions: This study showed the neuroprotective effects of NBO treatment by reducing oxidative stress and maintaining the level of connexin43 in astrocytes, which could be used for the clinical treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a substantial obstacle in cancer therapy. The microenvironment of solid tumor growth can be hypoxic, which promotes the survival, growth, and progression of cancer cells and reduces the effects of chemotherapy and radiotherapy. Hyperoxia treatment has potential to enhance cancer therapies. Objective: We evaluated whether normobaric hyperoxia (NBO) therapy has an anticancer effect and can be a strategy for overcoming anticancer drug resistance. Human alveolar adenocarcinoma (A549) and paclitaxel (PTX)-resistant (A549/PR) cell lines were used. Cells were assessed after exposure to room air (RA) or NBO for 48 h with and without PTX application. Results: NBO exposure inhibited cell viability, migration abilities, and proliferation in both cell lines. Chemo-resistant cell lines have shown variable viability upon NBO exposure. NBO exposure induced critical cytotoxicity and attenuated the characteristics of cancer in A549/PR cells. NBO induced a decline of chemoresistance in A549/PR cells when co-treated with PTX, consequently increasing cell death. In addition, NBO leads to intracellular reactive oxygen species and induced endoplasmic reticulum (ER) stress through the CCAAT/enhancer-binding protein homologous protein (CHOP) signaling pathway. Conclusion: In summary, NBO increased cell death in lung cancer cells and promoted PTX re-sensitization in A549/PR cells through apoptosis and CHOP-mediated ER stress. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke., Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed., Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO., Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)