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Obstructive sleep apnoea is characterized by chronic intermittent hypoxaemia and is independently associated with an increased risk of metabolic comorbidities (e.g. type II diabetes and ischaemic heart disease). These comorbidities could be attributable to hypoxaemia-induced alterations in blood lipid profiles. However, it remains unclear whether intermittent hypoxaemia alters triglyceridaemia differently between biological sexes. Therefore, we used a randomized crossover design to examine whether 6 h of moderate intermittent hypoxaemia (15 hypoxaemic cycles/h, 85% oxyhaemoglobin saturation) alters plasma triglyceride levels differently between men and women after a high-fat meal. Relative to men, women displayed lower levels of total triglycerides, in addition to denser triglyceride-rich lipoprotein triglycerides (TRL-TG; mainly very low-density lipoprotein triglycerides and chylomicron remnant triglycerides) and buoyant TRL-TG (mainly chylomicron triglycerides) during normoxia (ambient air) and intermittent hypoxaemia (sex × time: all P ≤ 0.008). Intermittent hypoxaemia led to higher triglyceride levels (condition: all P ≤ 0.016); however, this effect was observed only in men (sex × condition: all P ≤ 0.002). Compared with normoxia, glucose levels were higher in men and lower in women during intermittent hypoxaemia (sex × condition: P < 0.001). The different postprandial responses between biological sexes occurred despite similar reductions in mean oxyhaemoglobin saturation and similar elevations in insulin levels, non-esterified fatty acid levels and mean heart rate (sex × condition: all P ≥ 0.185). These results support growing evidence showing that intermittent hypoxaemia impacts men and women differently, and they might help to explain biological sex-related discrepancies in the rate of certain comorbidities associated with intermittent hypoxaemia. KEY POINTS: Intermittent hypoxaemia is a key characteristic of obstructive sleep apnoea and alters lipid metabolism in multiple tissues, resulting in increased circulating triglyceride levels, an important risk factor for cardiometabolic diseases. Circulating triglyceride levels are regulated differently between biological sexes, with women typically displaying much lower fasting and postprandial triglyceride levels than men, partly explaining why women of all ages experience lower mortality rates from cardiometabolic diseases. In this study, healthy young men and women consumed a high-fat meal and were then exposed to 6 h of intermittent hypoxaemia or ambient air. We show that postprandial triglyceride levels are significantly lower in women compared with men and that intermittent hypoxaemia leads to higher postprandial triglyceride levels in men only. These results might help us to understand better why women living with obstructive sleep apnoea experience lower rates of cardiometabolic diseases (e.g. type II diabetes and ischaemic heart disease) than men living with obstructive sleep apnoea., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

There is no study that has investigated the impact of exercise in a combined hypoxic and hot environment on endothelial function. Therefore, we tested whether aerobic exercise in a combined hypoxic and hot conditions induces further enhancement of endothelial function. Twelve healthy males cycled at a constant workload (50% of their maximal oxygen uptake under normoxic/thermoneutral conditions) for 30 min in four different environments: exercise under normoxic condition (NOR: fraction of inspiratory oxygen or FiO 2  = 20.9%, 20°C), exercise under hypoxic condition (HYP: FiO 2  = 14.5%, 20°C), exercise under hot condition (HOT: FiO 2  = 20.9%, 30°C), and exercise under combined hypoxia and hot conditions (HH: FiO 2  = 14.5%, 30°C). Before, during, and after exercise, cardiovascular variables (e.g., heart rate, blood flow, and shear rate), blood variables, and endothelial function evaluated by flow-mediated dilation (FMD) were assessed. Heart rates were significantly higher throughout the HH trial's experimental period than the other trials (p < 0.05). However, in the HH trial, brachial artery blood flow and shear rate did not differ from those in other trials after exercise. Plasma catecholamines (epinephrine, norepinephrine, and dopamine) elevations in response to exercise were significantly higher in the HH trial than in the other three trials (p < 0.05). No considerable differences were observed in FMD responses among trials before and after the exercise. In conclusion, aerobic exercise in a combined hot and hypoxic environment further activated sympathetic nervous activity but did not considerably enhance blood flow, shear rate, or endothelial function., (© 2024 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Rationale: Cannabis use is rapidly growing in the United States, but its health implications are poorly understood, particularly when compared with cigarette smoking. Previous research conducted on animal models or nonrepresentative populations with small sample sizes has yielded mixed results on the impact of marijuana use on hemoglobin concentrations, which might reflect subclinical hypoxemia and/or carbon monoxide exposure. Objectives: We evaluated the association between marijuana use and hemoglobin concentrations in a nationally representative sample of U.S. adults. Methods: This cross-sectional study included 16,038 individuals 18-59 years of age enrolled in National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We related current and former marijuana use with measured hemoglobin concentrations, with adjustment for demographics, education, housing, and cigarette smoking status in multivariable analyses that incorporated complex survey weights. As candidate positive and negative control exposures, we used similar methods to relate cigarette smoking and benzodiazepine use, respectively, with hemoglobin concentrations. Results: Current marijuana use was associated with significantly higher hemoglobin concentrations. After multivariable adjustment, compared with never use, current marijuana use was associated with a 0.111 (95% confidence interval, 0.021 to 0.201) g/dl higher hemoglobin concentration, whereas former use was associated with a 0.047 (95% confidence interval, -0.018 to 0.113) g/dl higher concentration (linear trend P  = 0.01). As hypothesized, cigarette smoking was also associated with higher hemoglobin concentrations, whereas benzodiazepine use was not. Conclusions: Among American adults, current marijuana use was associated with higher hemoglobin concentrations, as is cigarette smoking but not benzodiazepine use. These results suggest the possibility that marijuana smoking induces subclinical hypoxemia stimulating hemoglobin production. Further confirmation of this observational finding is needed in light of the increasing medical and recreational use of smoked marijuana products.

Objectives: To validate a method for continuously estimating the Pao 2 /Fio 2 (PF) ratio in all critically ill pediatric patients using only standard continuous data monitoring., Design: Retrospective study on a high temporal resolution database., Setting: PICU in Montreal, QC, Canada., Patients/subjects: We included any patients admitted from May 2015 to May 2023 who had an arterial blood gas (ABG) with concurrent continuous pulsed oximetry saturation (Spo 2 ) values. We used our previously validated mathematical model to determine the magnitude of hypoxemia by computing the estimated ePao 2 /Fio 2 (ePF) ratio and comparing it to the Spo 2 /Fio 2 (SF), using PF ratio as the reference standard., Interventions: None., Measurements and Main Results: We analyzed a total of 20,828 ABGs. When Spo 2 was below or equal to 97%, the ePF ratio showed a significantly better hypoxemia classification (none, light/moderate, or severe) than the SF ratio (0.80 vs. 0.72; p < 0.001), a lower fixed bias (16.26 vs. -35.24; p < 0.001), a lower mean absolute error (37.92 vs. 63.93; p < 0.001) and a lower proportional bias (slope of 1.01 vs. 0.81; p < 0.001). ePF ratio has also a better limits of agreement difference from Bland-Altman plot (248.10 vs. 292.45; p < 0.001) and coefficient of determination (0.68 vs. 0.59; p < 0.001). When Spo 2 was above 97%, the ePF ratio had better classification with Kappa (0.53 vs. 0.43; p < 0.001) and lower fixed bias (-0.63 vs. 65.68; p < 0.001)., Conclusions: The PF ratio based on ePF allows for a continuous estimation of hypoxemia severity with a better performance than the SF ratio., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Pulse oximetry is a standart of anesthesia for perioperative monitoring. Due to the principles of Hb oxygen dissociation curve, peripheral oxygen saturation has an approximate sensitivity and specificity of 90% for the detection of hypoxemia., Objectives: The primary outcome of the study was to evaluate ORi Ⓡ as an early parameter to determine hypoxia in morbidly obese patients. The secondary outcome was to compare the effectiveness of ORi Ⓡ with SpO 2 in non-obese patients., Design: Prospective, observational study., Setting: Department of elective operating room at tertiary hospital., Patients and Methods: Observational study included written informed consent from 51 patients with 19 < BMI < 25 kg/m 2 and 51 patients with BMI > 40 kg/m 2 undergoing an elective surgery requiring tracheal intubation. In addition to standard monitors, an ORi sensor was placed and baseline values were recorded. The patients were preoxygenated until end tidal expiratory oxygen concentration is reached to 90%. After anesthesia induction and tracheal intubation, the breathing circuit was not connected tracheal tube until the SpO 2 decreased to 95%. Shapiro-Wilk, Pearson Chi-square, t-test, and Mann Whitney U test were used for the study., Main Outcome Measures: Times of tolerable apnea, ORi Ⓡ and SpO 2 values at the end of preoxygenation, beginning of intubation, beginning of the ORi alarm, when SpO 2 reached 95%, and when ORi reaches a plateau., Sample Size: 102 patients., Results: The alert period: time to reach ORi Ⓡ from 0.24 to a value of 95% SpO 2 was observed as 32 s in morbidly obese patients and 94 s in patients with a normal body mass index. The SpO 2 alert period was determined as time difference between 97% and 95% SpO 2 . The data were recorded as 15 s and 36 s, respectively. It was observed that tolerable apnea, ORi Ⓡ , SpO 2 and added alert times were longer in patients with normal BMI compared to morbidly obese patients., Conclusions: As a result, ORi Ⓡ can provide an early warning to prevent unexpected hypoxia before saturation begins to decrease in morbidly obese patients., Limitations: Inability to perform arterial blood gas sampling in the time periods when we looked at the parameters to determine the relationship between ORi Ⓡ and PaO 2 ., Gov Identifier: NCT05480748 registered 2022-07-29., (© 2024. The Author(s).)

An actin binding protein, gelsolin (GSN) has two isoforms, plasma (pGSN) and cytosolic (cGSN). Changes in pGSN and/or cGSN levels have been shown to be associated with the pathogenesis of several diseases. The aim of this study was to evaluate changes in intracellular and extracellular GSNlevels with HIF-1 in animals exposed to chronic sustained hypoxia (CSH), in addition to apoptosis and the cellular redox status. The rats in the Sham group were exposed to 21% O 2 , and the rats in the hypoxia groups were exposed to 13 and 10% O 2 , respectively. Plasma pGSN, HIF-1α, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS), and lung tissue pGSN, HIF-1α, TAS, TOS, GSN levels, and apoptotic cell numbers were measured. HIF-1α levels were found to increase significantly in the tissue, especially in the group with severe hypoxia, both in biochemical and histological examinations. pGSN levels were also significantly decreased in both plasma and tissue. Significant increases in tissue were observed in cGSN. It was observed that while the antioxidant activity was dominant in the tissue, the oxidant activity was dominant in the plasma. In particular, the response to hypoxia regulated by HIF-1 is very important for cellular survival. The results of this study showed that the increase in cGSN and TAS levels in the lung tissue together with HIF-1α can be considered as the activation of mechanisms for cellular protection., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Deformability and sickling of red blood cells (RBCs) from individuals with sickle cell trait (SCT) was evaluated under harsh biophysical conditions that mimic certain vascular beds in vivo. RBC deformability in osmotic-gradient ektacytometry was decreased in HbAS (SCT) compared to HbAA (wild-type) RBCs at supraphysiological osmolalities. RBC deformability was also measured by oxygen-gradient ektacytometry. Whereas RBC sickling was not observed under isotonic and neutral pH conditions, hypertonicity and acidosis alone or in combination induced reversible sickling of SCT RBC. These data suggest that hyperosmolality and/or acidosis enhance hypoxia-induced sickling of SCT RBC., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Surprisingly, despite the high prevalence of metformin use in type 2 diabetes (T2D) patients with heart disease, limited safety data is available regarding metformin use in patients with acute and critical heart disease., Methods: In this single-center retrospective study, patients admitted to the cardiology department for heart failure (HF) or acute coronary syndrome (ACS) between December 2013 and December 2021 and who underwent arterial blood gas analysis at admission with an estimated glomerular clearance rate of ≥45 ml/min/1.73 m 2 were identified. The incidences of hyperlactatemia, acidosis, and 30-day in-hospital mortality were compared between preadmission metformin users and nonusers., Results: Of 526 admissions, 193/193 metformin users/nonusers were selected in a propensity score-matched model. Metformin users had greater lactate levels (2.55 ± 2.07 mmol/l vs. 2.00 ± 1.80 mmol/l P < 0.01), a greater incidence of hyperlactatemia [odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.63-3.98; P < 0.01] and acidosis (OR = 1.78; 95% CI, 1.00-3.16; P < 0.05) at admission and a greater incidence of in-hospital mortality (OR = 3.83; 95% CI, 1.05-13.94; P < 0.05), especially those with HF/acute myocardial infarction, elderly age, or without preadmission insulin use., Conclusions: Our results suggest that, compared to metformin nonusers, preadmission use of metformin may be associated with a greater incidence of hyperlactatemia and acidosis at admission and greater 30-day in-hospital mortality among T2D patients with HF or ACS at high risk of hypoxia, particularly those without preadmission insulin use. The safety of metformin in this population needs to be confirmed in prospective controlled trials., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression ( IL-6 , TNFα , CXCL8 , ISG15 , IFIT1 , RIGI , IFNβ , CCL5 , and CXCL10 ) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO 2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLS-DA). We found that 26 of 121 children had severe hypoxemia (SpO 2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q -value < 0.05], and ISG15 , IFIT1 , RIGI , IFNβ , CCL5 , and CXCL10 were underexpressed (FC <0.5; q -value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8 , ISG15 , IFIT1 , RIGI , and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pita-Martínez, Goez-Sanz, Virseda-Berdices, Gonzalez-Praetorius, Mazario-Martín, Rodriguez-Mesa, Quero-Delgado, Matías, Martínez and Resino.)

Background: Identification of hypoxaemia and hypercapnia is essential for the diagnosis and treatment of acute respiratory failure. While arterial blood gas (ABG) analysis is standard for PO 2 and PCO 2 measurement, venous blood gas (VBG) analysis is increasingly used as an alternative. Previous systematic reviews established that VBG reporting of PO 2 and PCO 2 is less accurate, but the impacts on clinical management and patient outcomes are unknown., Aims: This study aimed to systematically review available evidence of the clinical impacts of using ABGs or VBGs and examine the arteriovenous difference in blood gas parameters., Methods: A comprehensive search of the MEDLINE, Embase and Cochrane Library databases since inception was conducted. Included studies were prospective or cross-sectional studies comparing peripheral ABG to peripheral VBG in adult non-critical care inpatients presenting with respiratory symptoms., Results: Of 15 119 articles screened, 15 were included. No studies were found that examined clinical impacts resulting from using VBG compared to ABG. Included studies focused on the agreement between ABG and VBG measurements of pH, PO 2 , PCO 2 and HCO 3 - . Due to the heterogeneity of the included studies, qualitative evidence synthesis was performed. While the arteriovenous difference in pH and HCO 3 - was generally predictable, the difference in PO 2 and PCO 2 was more significant and less predictable., Conclusions: Our study reinforces the notion that VBG is not comparable to ABG for physiological measurements. However, a key revelation from our research is the significant lack of data regarding the clinical implications of using VBG instead of ABG, a common scenario in clinical practice. This highlights a critical knowledge gap., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Introduction: Hypoxia is a significant cause of secondary insult in the critically ill trauma or surgical patient. The cause of increased mortality following a brief period of hypoxia is not well understood. The aim of this study is to determine the effect of acute, isolated deviations in oxygen concentration on proinflammatory cytokine release and markers of endothelial stress in a murine model., Methods: Mice were randomized to either control, hypoxia, or hyperoxia group. The control group was exposed to room air for 60 min, the hyperoxia group was exposed to 70% fraction of inspired oxygen, and the hypoxia group was exposed to 10% fraction of inspired oxygen for 60 min. Whole blood collection was completed via cardiac puncture. Serum concentrations of proinflammatory cytokines and endothelial stress markers were analyzed via enzyme-linked immunosorbent assay., Results: Following exposure to hypoxic conditions, there was a significant increase in interleukin (IL)-1α (IL-1 α), IL-1 β, IL-3, IL-4, IL-6, IL-10, tumor necrosis factor α . Following exposure to hyperoxic conditions, there was a significant increase in monocyte chemoattractant protein-1 and regulated upon activation normal T cell expressed and presumably secreted, as well as a significant decrease in IL-12, and IL-17. No clinically significant difference was noted in serum concentration of endothelial stress markers between the treatment groups., Discussion: Exposure to oxygen extremes induces systemic inflammation as measured by proinflammatory cytokines in a murine model. Hyperoxia also demonstrates the ability to downregulate certain inflammatory pathways while inducing others. No effect on serum concentration of endothelial stress markers is observed following acute, isolated hypoxic or hyperoxic conditions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery., Objective: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less., Design: Randomised controlled trial., Setting: A tertiary care paediatric hospital., Participants: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery., Intervention: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively., Main Outcome Measure: The primary outcome was the incidence of SpO2 90% or less during the surgery., Results: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031)., Conclusion: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear., Objective: To investigate the association between the exposure to particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children., Design: Retrospective study., Setting: Single-centre., Participants: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020., Intervention: Information on daily levels of particulate matter with a diameter 10 μm or less and 2.5 μm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data., Main Outcome Measures: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals., Results: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 μm or less in diameter (≥81 μg m -3 , 17/275, 6.2%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 μg m -3 , 472/12 900, 3.7%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P  = 0.035]., Conclusion: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 μm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Purpose: The purpose of this study was to evaluate the accuracy of peripheral oxygen saturation (SpO 2 ) measurements from Polar Elixir™ pulse oximetry technology compared with arterial oxygen saturation (SaO 2 ) measurements during acute stepwise steady-state inspired hypoxia at rest. A post hoc objective was to determine if SpO 2 measurements could be improved by recalibrating the Polar Elixir™ algorithm with SaO 2 values from a random subset of participants., Methods: The International Organization for Standardization (ISO) protocol (ISO 80601-2-61:2017) for evaluating the SpO 2 accuracy of pulse oximeter equipment was followed whereby five plateaus of SaO 2 between 70% and 100% were achieved using stepwise reductions in inspired O 2 during supine rest. Blood samples drawn through a radial arterial catheter from 25 participants were first used to compare SaO 2 with SpO 2 measurements from Polar Elixir™. Then the Polar Elixir™ algorithm was recalibrated using SaO 2 data from 13 random participants, and SpO 2 estimates were recalculated for the other 12 participants. For SaO 2 values between 70% and 100%, root mean square error, intraclass correlation coefficients (ICC), Pearson correlations, and Bland-Altman plots were used to assess the accuracy, agreement, and strength of relationship between SaO 2 values and SpO 2 values from Polar Elixir™., Results: The initial root mean square error for Polar Elixir™ was 4.13%. After recalibrating the algorithm, the RMSE was improved to 2.67%. The ICC revealed excellent levels of agreement between SaO 2 and Polar Elixir™ SpO 2 values both before (ICC(1,3) = 0.837, df = 574, P < 0.001) and after (ICC(1,3) = 0.942, df = 287, P < 0.001) recalibration., Conclusions: Relative to ISO standards, Polar Elixir™ yielded accurate SpO 2 measurements during stepwise inspired hypoxia at rest when compared with SaO 2 values, which were improved by recalibrating the algorithm using a subset of the SaO 2 data., (Copyright © 2024 by the American College of Sports Medicine.)

The embryonic chicken is a valuable model for studying the maturation of cardiovascular physiology and the responses of this organ system to environmental manipulations such as acute hypoxia. Hypoxia determines not only the general cardiovascular response but also is a tool to determine the system's maturation of reflexive control. Several studies suggest embryonic chicken's regulation of the cardiovascular response to hypoxia, but no studies have measured the blood chemistry changes that accompany these responses. To clarify the changes in blood parameters accompanying cardiovascular function changes during acute hypoxia, we designed a study to investigate the blood chemistry (pO 2 , pCO 2 , pH, lactate, glucose, and blood ions) in developing embryos during acute hypoxia (O 2  = 10 %). Embryos ranging from day 13 to 21 of incubation were sampled during a control period and at the end of a 5-min of hypoxia. Hypoxia caused bradycardia on all days of incubation. The maximal blood hypoxic response occurred on day 15, with lactate increasing 7-fold (2.5 to 16.6 mmol/l) while glucose levels decreased by 50 % (136 to 63 mg/dl). Furthermore, hypoxia reduced pH (7.40 to 7.26), which peaked on day 15. These data indicate that a 5-min exposure to 10 % O 2 is sufficient to induce dramatic changes in blood chemistry however chorioallantoic arterial blood pO 2 was unchanged on most days of the study. Therefore, given the cardiovascular response to hypoxia and the increase in blood lactate prior to airbreathing in the chicken embryo, the embryonic tissues experienced an acute stress that may be the basis for the change in cardiovascular function during the exposure., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Back to the sources, postoperative nausea and vomiting, hypo- and hypertension, heart rate alterations, and hypoxemia due to laryngospasm might be considered perioperative complications., Methods: This cross-sectional study was conducted at an Education and Research Hospital between January 2018 and June 2023. The study included a total of 437 cases of thyroid surgery. The demographic data such as age, sex, co-morbidities of the instances, hypotension, hypertension, bradycardia, hypoxemia, and postoperative nausea and vomiting, as well as laboratory data were obtained and analyzed., Results: Of 437 cases, 334 (76%) were females and 103 (24%) were males, with a mean age of 51.83±11.91 years and 55.32±11.87 years, respectively. No statistical significance was realized between the complications, co-morbid diseases, and age. Notably, no liaison between the complications after awakening from the anesthesia and preoperative laboratory parameters was discerned. However, a high but no significant relationship was revealed between the platelet-to-lymphocyte ratio (P/L) in cases with hypoxemia and hypotension. Finally, no significance between laboratory values, bradycardia, hypertension, and postoperative nausea and vomiting was distinguished., Conclusion: We postulate that the so-called inflammatory biomarkers measured at the time of preoperative examination in the blood count concept selectively do not enrich for anticipating complications that arise in the perioperative echelon.

Spontaneous and stimulated production of cytokines by peripheral blood cells obtained from the caudal vein of male Wistar rats was assessed before testing their resistance to oxygen deficiency in a decompression chamber. To study the spontaneous production of cytokines, heparinized blood cells were incubated in a culture medium (24 h, 5% CO 2 , 37°C) and the content of proinflammatory cytokines IL-6 and TNFα and anti-inflammatory IL-10 in the culture medium was assessed by ELISA. To stimulate cytokine production, blood cells were incubated for 24 h with LPS, phytohemagglutinin, and concanavalin A at final concentrations of 2, 4, and 4 μg, respectively. Two weeks after blood sampling, individual resistance of the animals to hypoxia in a decompression chamber was determined. In animals with low resistance to hypoxia, the levels of spontaneous production of all three cytokines were significantly higher, while after stimulation, the level of IL-1β increased by more than 2 times. The animals with spontaneous production of IL-10>50 pg/ml, IL-6>10 pg/ml, and TNFα>10 pg/ml, as well as with the increase in IL-1β production by more than 2 times upon stimulation were classified as low-resistant. At IL-10<15 pg/ml, IL-6<9 pg/ml, and TNFα<7 pg/ml, as well as the absence of the increase in IL-1β production upon stimulation, they were classified as high-resistant. The identified features of spontaneous and stimulated production of cytokines can be used as non-invasive biomarkers to determine the resistance to hypoxia without exposure to sublethal hypoxia in a decompression chamber., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO 2 ] 90-93%) and severe hypoxaemia (ie, SpO 2 <90%). We suggest that moderate hypoxaemia in the primary care setting should prompt careful clinical re-assessment, consideration of referral, and close follow-up. We provide practical guidance to better support front-line health-care workers to use pulse oximetry, including rethinking traditional binary SpO 2 thresholds and promoting a more nuanced approach to identification and emergency treatment of the severely ill child., Competing Interests: Declaration of interests All authors have received institutional fellowship or grant funding related to pulse oximetry and oxygen research, including funding to conduct the original studies reanalysed in this Viewpoint: Save the Children UK (AGF, TC, CK, and HRG); Bill & Melinda Gates Foundation (AGF, TD, HRG, YK, EDM, AHB, SA, and TC); ELMA Philantrophies (YK); Swedish Research Council (HH, CK, and EDM); Einhorn Family Foundation (HH); Wellcome Trust (TC, CK, and EDM); National Institutes of Health (EDM and SH); WHO (TC, EDM, AHB, SA, and TC); United States Agency for International Development (EDM); US Centers for Disease Control and Prevention (EDM); Thrasher Research Fund (EDM); Moderna (EDM); National Health and Medical Research Council (HRG); and Royal Children's Hospital Foundation (HRG). YK is employed by Clinton Health Access Initiative, which contributes to global pulse oximetry and oxygen strategy. TC has received consulting fees from the UN and chairs a steering committee for an adolescent mental health trial in Nepal. HRG and EDM have served as advisers to the Tools for Integrated Management of Childhood Illness–Améliorer l'Identification des détresses Respiratoires chez l'Enfant (AIRE) pulse oximetry trial. EDM co-chairs the Union Child Pneumonia Working Group; HRG and CK co-chair the Lancet Global Health Commission on Medical Oxygen. AGF and HRG are board members for Oxygen for Life Initiative, a non-profit research and implementation group for pulse oximetry and oxygen. HRG, CK, and EDM have served as advisers to Lifebox Foundation, a non-governmental organisation that aims to increases access to pulse oximetry., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Skin pigmentation influences peripheral oxygen saturation (SpO 2 ) compared to arterial saturation of oxygen (SaO 2 ). Occult hypoxemia (SaO 2  ≤ 88% with SpO 2  ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO 2 -SaO 2 discrepancy due to significant hemolysis., Methods: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO 2 and SaO 2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018-5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO 2 -SaO 2 calculations., Results: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively). In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95% CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95% CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08-1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia., Conclusion: SaO 2 should be carefully monitored if using SpO 2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We sought to determine the effects of acute simulated altitude on the maximal lactate steady state (MLSS) and physiological responses to cycling at and 10 W above the MLSS-associated power output (PO) (MLSS p and MLSS p+10 , respectively). Eleven (4 females) participants (means [SD]; 28 [4] yr; V̇o 2max : 54.3 [6.9] mL·kg -1 ·min -1 ) acclimatized to ∼1,100 m performed 30-min constant PO trials in simulated altitudes of 0 m sea level (SL), 1,111 m mild altitude (MILD), and 2,222 m moderate altitude (MOD). MLSS p , defined as the highest PO with stable (<1 mM change) blood lactate concentration ([BLa]) between 10 and 30 min, was significantly lower in MOD (209 [54] W) compared with SL (230 [56] W; P < 0.001) and MILD (225 [58] W; P = 0.001), but MILD and SL were not different ( P = 0.12). V̇o 2 and V̇co 2 decreased at higher simulated altitudes due to lower POs ( P < 0.05), but other end-exercise physiological responses (e.g., [BLa], ventilation [V̇e], heart rate [HR]) were not different between conditions at MLSS p or MLSS p + 10 ( P > 0.05). At the same absolute intensity (MLSS p for MILD), [BLa], HR, and V̇ E and all perceptual variables were exacerbated in MOD compared with SL and MILD ( P < 0.05). Maximum voluntary contraction, voluntary activation, and potentiated twitch forces were exacerbated at MLSS p + 10 relative to MLSS p within conditions ( P < 0.05); however, condition did not affect performance fatiguability at the same relative or absolute intensity ( P > 0.05). As MLSS p decreased in hypoxia, adjustments in PO are needed to ensure the same relative intensity across altitudes, but common indices of exercise intensity may facilitate exercise prescription and monitoring in hypoxia. NEW & NOTEWORTHY This study demonstrates the power output and metabolic rate associated with the maximal lactate steady-state (MLSS) decline in response to simulated altitude; however, common indices of exercise intensity remained unchanged when cycling was performed at the work rate associated with MLSS at each simulated altitude. These results support previous studies that investigated the effects of hypoxia on alternative measures of the critical intensity of exercise and will inform exercise prescription/monitoring across altitudes.

Pulse oximetry is arguably the most impactful monitor ever introduced into respiratory care practice. Recently there has been increased attention to the problem of occult hypoxemia in which patients are hypoxemic despite an acceptable S pO 2 Although occult hypoxemia might be greater in Black patients than white patients, it is not insignificant in whites. In a given population of patients, the bias between S pO 2 and arterial oxygen saturation (S aO 2 ) might be close to zero. However, the limits of agreement can be wide, meaning that S pO 2 might overestimate S aO 2 in many individual patients, which can result in occult hypoxemia in some. Manufactures report accuracy of S pO 2 derived from normal individuals, which might differ from that in the clinical setting. That S pO 2 overestimates S aO 2 in an important number of individuals has caused some to recommend higher S pO 2 targets to avoid occult hypoxemia. There is also evidence that suggests that S pO 2 might not accurately trend S aO 2 Additional research is needed to investigate strategies to mitigate the bias between S pO 2 and S aO 2 Clinicians must be cognizant of the limitations of pulse oximetry when clinically using S pO 2 The aim of this paper is to provide an update on pulse oximetry., Competing Interests: Dr Hess discloses relationships with Daedalus Enterprises, American Association for Respiratory Care, Massachusetts General Hospital, Northeastern University, University of Pittsburgh, Lungpacer, Jones & Bartlett, McGraw Hill, and UpToDate. Dr Hess is Managing Editor of Respiratory Care., (Copyright © 2024 by Daedalus Enterprises.)

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO 2 ] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO 2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO 2 ( p < 0.001, η p 2 = 0.747) and increased heart rate ( p = 0.006, η p 2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum ( p < 0.001, η p 2 = 0.581) and plasma ( p < 0.001, η p 2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min ( p = 0.018) in serum and after 30 min ( p = 0.040) and 90 min ( p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO 2 ) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO 2 to "back-up FiO 2 " during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO 2 before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a "backup FiO 2 " (which reflects FiO 2 -requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www., Clinicaltrials: gov under the registration no. NCT03785899., What Is Known: • Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states. • Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range., What Is New: • Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery. • FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots., (© 2024. The Author(s).)

Background: Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes., Methods: Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls. We targeted pre- and post-op absolute serum quantification of 9 key members of the arginine metabolism pathway by tandem mass spectrometry. Primary outcomes were length of stay (LOS) and post-Stage 2 hypoxemia., Results: Pre-op cases showed alteration in 6 metabolites including decreased arginine and increased asymmetric dimethyl arginine (ADMA) levels compared to controls. Post-op cases demonstrated decreased arginine and citrulline levels persisting through 48 h. Adjusting for clinical variables, lower pre-op and 2 h post-op concentrations of multiple metabolites, including arginine and citrulline, were associated with longer post-op LOS (p < 0.01). Increased ADMA at 24 h was associated with greater post-op hypoxemia burden (p < 0.05)., Conclusion: Arginine metabolism is impaired in interstage SVHD infants and is further deranged following Stage 2 palliation. Patients with greater metabolite alterations experience greater post-op morbidity. Decreased arginine metabolism may be an important driver of pathology in SVHD., Impact: Interstage infants with SVHD have significantly altered arginine-nitric oxide metabolism compared to healthy children with deficiency of multiple pathway intermediates persisting through 48 h post-Stage 2 palliation. After controlling for clinical covariates and classic catheterization-derived predictors of Stage 2 readiness, both lower pre-operation and lower post-operation circulating metabolite levels were associated with longer post-Stage 2 LOS while increased post-Stage 2 ADMA concentration was associated with greater post-op hypoxemia. Arginine metabolism mapping offers potential for development using personalized medicine strategies as a biomarker of Stage 2 readiness and therapeutic target to improve pulmonary vascular health in infants with SVHD., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D., Methods: This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90 non - specific ), T90 associated with acute oxygen desaturation (T90 desaturation ) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease., Results: Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90 desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90 non-specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD., Conclusion: While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease., (© 2024. The Author(s).)

Objectives: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata., Design: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata., Setting: Twenty-five PICUs across the United States., Patients: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data., Interventions: None., Measurements and Main Results: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS., Conclusions: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches., Competing Interests: This work was supported by grant R21HD096402 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (Dr. Sanchez-Pinto). Drs. Atreya and Sanchez-Pinto received funding from R21GM151703. Cincinnati Children’s Hospital Medical Center (CCHMC) and the estate of the late Dr. Hector Wong hold patents for the pediatric sepsis biomarker risk model (PERSEVERE) for risk stratification of pediatric sepsis patients and gene expression-based adaptive endotypes. Dr. Atreya received funding from the National Institute of Child Health and Human Development (NICHD) (R21HD096402) and the National Institute of General Medical Sciences, he disclosed he holds patents for the pediatric sepsis biomarker risk model (PERSEVERE) for risk stratification of pediatric sepsis patients and gene expression-based adaptive endotypes. Drs. Atreya, Bennett, Faustino, Lufti, and Sanchez-Pinto received support for article research from the National Institutes of Health (NIH). Dr. Bennett’s institution received funding from the NICHD, the National Center for Advancing Translational Sciences, and the National Heart, Lung, and Blood Institute. Drs. Faustino and Sanchez-Pinto’s institutions received funding from the NIH. Dr. Cvijanovich’s institution received funding from CCHMC, Boston Children’s Hospital, the Centers for Disease Control, and Nationwide Children’s Hospital. Dr. Thomas received funding from Bayer AG. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia ([Formula: see text] = 0.21) or normobaric hypoxia ([Formula: see text] = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI. NEW & NOTEWORTHY Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures.

Objective: To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs., Methods: A prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI., Results: A total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p<0.001) was observed. The OSI cut-off value for predicting an OI of >15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05)., Conclusion: The findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Bui-Binh-Bao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost., Methods: Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2)., Results: SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2., Conclusions: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL., (© 2024. The Author(s).)

Objectives: Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown., Methods: We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles., Results: The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.058, P = 0.011), total cholesterol (TC) (β = 0.100, P < 0.001), total triglycerides (TG) (β = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (β = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (β = 0.051, P = 0.049), apolipoprotein B (apoB) (β = 0.136, P < 0.001), apolipoprotein E (apoE) (β = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles., Conclusions: We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA., Trial Registration: ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China., (© 2024. The Author(s).)

Objective: To explore the association between PaCO 2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure., Methods: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure., Results: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO 2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO 2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO 2  ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO 2 >32 mmHg were set as reference. In patients with PaCO 2  ≤ 32 mmHg, one unit increment of PaCO 2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO 2 >32 mmHg., Conclusions: PaCO 2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO 2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point., (© 2024. The Author(s).)

Background: Obstructive sleep apnea (OSA) is one of the risk factors for diabetes mellitus type 2 (DM2). As OSA is associated with the disruption of the circadian rhythm, it affects circadian clock proteins, including neuronal PAS domain protein 2 (NPAS2) and nuclear receptor subfamily 1 group D member 1 (Rev-Erb-α). These proteins have been shown to be related to metabolic abnormalities, i.a., insulin resistance., Objectives: The present pilot study aimed to investigate the NPAS2 and Rev-Erb-α protein serum levels in the groups of patients with severe OSA and severe OSA+DM2 in comparison with healthy controls, taking into account correlations with polysomnography (PSG) parameters (e.g., oxygen saturation (SpO2) variables)., Material and Methods: A total of 40 participants were included in the study. They were split into 3 groups as follows: the OSA group (n = 17; apnea-hypopnea index (AHI) >30, no DM2); the OSA+DM2 group (n = 7; AHI > 30 and DM2); and the control group (n = 16; AHI < 5, no DM2). All participants underwent a nocturnal PSG examination and had their blood collected the following morning. The serum levels of NPAS2 and Rev-Erb-α proteins were assessed using the enzyme-linked immunosorbent assay (ELISA)., Results: The mean NPAS2 protein level was significantly lower in the OSA group as compared to healthy individuals (p = 0.017). Additionally, the OSA group presented with lower NPAS2 protein levels as compared to the OSA+DM2 group, but only a tendency was observed (p = 0.094). No differences in the Rev-Erb-α protein concentration were noticed. Furthermore, a negative correlation between AHI during rapid eye movement (REM) sleep and the NPAS2 protein serum level was observed (r = -0.478; p = 0.002)., Conclusions: Serum NPAS2 protein might be involved in metabolic dysregulation present among OSA patients, while the mechanism itself may be associated with REM sleep.

Background: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes., Methods: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO 2 :FiO 2  > 300 or (ii) SpO2: FiO 2  > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described., Results: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001)., Conclusions: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials., (© 2024. The Author(s).)

Objective: To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS)., Material and Methods: We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge., Results: We found a direct correlation between the duration of hypoxemia with SpO 2 less than 90% ( r =0.327, p =0.035) and less than 85% ( r =0.461, p =0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value ( r =-0.328, p =0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO 2 less than 85% ( r =-0.389, p =0.028). A regression model showed that BDNF level was associated with the minimum SpO 2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index., Conclusion: The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.

Background: Hypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China., Methods: Anonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI., Results: A total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14-24 mmol/L (calculated using Hoffmann and refineR) and 15-24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14-25 mmol/L (calculated using Hoffmann and Bhattacharya), 16-23 mmol/L (EM), 15-24 mmol/L (kosmic), and 14.2-24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14-24 mmol/L (calculated using Hoffmann and refineR), 15-24 mmol/L (Bhattacharya and kosmic), and 15-23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22-29 mmol/L) that was provided by the manufacturer., Conclusion: The tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy., Material and Methods: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG 1 ), n =35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG 2 ) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent., Results: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG 2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG 1 , after treatment it was 0.07 (0.06; 0.09) in the MG 2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG 1 and MG 2 ., Conclusion: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

Background: Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia., Objective: The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020., Methods: This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005., Results: The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005)., Conclusion: HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future., Competing Interests: There are no conflicts of interest., (© 2022 Rusdiana Rusdiana, Ahmad Moradi, Sry Suryani Widjaja, Mutiara Indah Sari, Hidayat Hidayat, Maya Savira,Rina Amelia, Rusmalawaty Rusmalawaty.)

Objectives: This research aims to study the prognostic role of serum S100 as a predictor of mortality in vascular and traumatic brain injuries., Methods: This prospective cohort study involved 219 patients. In the blood serum, neuron-specific markers (S100, NSE) and glucose, acid-base state and gas composition of arterial blood were obtained at admission, on the 3rd, 5th and 7th days of patients' stay in the intensive care unit., Results: The most significant risk factor for an unfavorable outcome is the marker S100 with a cut-off point of 0.2 mcg/l. The analysis results indicate a statistically significant direct relationship between S100 > 0.2 mcg/l and NSE ≥ 18.9 ng/ml compared to other variables, while the chance ratio (OR) is 11.9 (95%CI:3.2927-1.6693;). With blood sugar increase above 7.4 mmol/l, the OR is 3.82 (95% CI: 2.1289-0.5539;); with a Glasgow scale below 13 points, the OR is 3.69 (95% CI: 2.1316-0.4819;); with an increase in pCO2 < 43.5 mm Hg, the OR was 3.15 (95% CI: 1.8916- 0.4062;). The obtained model certainty measure according to pseudo R2 Nagelkerke criterion is 263.5, showing the excellent quality of the mathematical model's predictive ability. The developed prognostic model, including the dependent variable S100 and independent variables as predictors of a poor outcome of NSE, pCO2, GCS and Hb, reached a cut-off point of 84.51%, AUC - 0.88 with high levels of sensitivity and specificity: 91.89% and 64.14%, respectively., Novelty: This model can be used to predict the outcome in patients with acute cerebral pathology.

Background Inadequate pulmonary vascular growth results in morbidity for many children with single-ventricle heart disease (SVHD). Endothelin 1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle proliferation. Circulating ET1 levels and their association with outcomes have not been studied during early SVHD palliation. We aimed to define circulating levels of ET1 in patients with SVHD undergoing stage 2 palliation and evaluate their relationship to postoperative hypoxemia. We hypothesized that patients with SVHD with higher ET1 concentration would have a greater post-stage 2 hypoxemia. Methods and Results Prospective cohort study of 55 subjects with SVHD undergoing stage 2 palliation and 50 controls. Samples for ET1 analysis were collected at preoperation (systemic and pulmonary vein) and 2, 24, and 48 hours postoperation for cases and a single time point for controls. The primary outcome was percentage of first 48 postoperative hours with clinically significant hypoxemia (saturation, <70%). ET1 concentration was lower in preoperative cases than controls (2.2 versus 2.7 pg/mL; P =0.0015) and in the pulmonary vein than systemic vein (1.7 versus 2.2 pg/mL; P <0.001). ET1 level increased by 2 hours postoperation and trended back to baseline by 48 hours. Higher preoperative pulmonary vein ET1 and 2 hours postoperative ET1 were associated with larger hypoxemia burden (10.6% versus 2.7% [ P =0.0081]; and 7.6% versus 3.2% [ P =0.01], respectively). Multivariable testing demonstrated ET1 concentration and cardiopulmonary bypass time were associated with hypoxemia, whereas catheterization measurements and clinical variables were not. Conclusions Infants with SVHD with higher perioperative ET1 concentration experience more post-stage 2 hypoxemia. ET1 activity may be a modifiable risk factor of pulmonary vascular inadequacy for stage 2 palliation.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO 2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl- β -hexosaminidase, ↑ β -glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min-normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min-hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects., Competing Interests: There is no conflict of interests., (Copyright © 2022 Mateusz Maciejczyk et al.)

Objective: Hypoxia induces interleukin-6 (IL-6) production in obstructive sleep apnea syndrome (OSAS). Low serum 25 hydroxyvitamin D (25(OH)D) levels have been linked to OSAS susceptibility. Serum 25(OH)D levels have been negatively correlated with serum IL-6 levels in patients with chronic inflammation. No data exist to assess whether there is a correlation between 25(OH)D and IL-6 serum levels in OSAS, while the impact of continuous positive airway pressure (CPAP) therapy on IL-6 or 25(OH)D levels needs further investigation. We aimed to compare the serum 25(OH)D and IL-6 levels between OSAS patients and controls, examine a possible correlation between 25(OH)D and IL-6 levels and the changes of their concentrations after twelve months of CPAP therapy in OSAS patients., Methods: 15 newly-diagnosed OSAS patients and 15 non-apneic controls were recruited. Serum IL-6 and 25(OH)D levels were measured in the study population at baseline and twelve months after CPAP initiation in OSAS patients., Results: IL-6 levels were elevated in OSAS patients than controls and were positively and negatively correlated with body mass index (BMI) and minimum oxyhemoglobin saturation (minSpO 2 ), respectively. Diabetes mellitus, BMI and minSpO 2 independently predicted IL-6 levels. No difference was found in 25(OH)D levels between groups. No correlation between IL-6 and 25(OH)D levels was detected. Effective CPAP therapy did not impact IL-6 or 25(OH)D levels after one year in OSAS patients., Conclusions: No correlation between IL-6 and 25(OH)D levels was found. IL-6 levels were significantly elevated in OSAS patients than the controls and positively correlated with BMI, diabetes mellitus, and nocturnal hypoxemia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m -2 ] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m -2 ) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

This study investigated the 30-days altitude training (2500 m, LHTH-live and training high) on hematological responses and aerobic-anaerobic performances parameters of high-level Paralympic athletes. Aerobic capacity was assessed by 3000 m run, and anaerobic variables (velocity, force and mechanical power) by a maximal 30-s semi-tethered running test (AO30). These assessments were carried out at low altitude before (PRE) and after LHTH (5-6 and 15-16 days, POST1 and POST2, respectively). During LHTH, hematological analyzes were performed on days 1, 12, 20 and 30. After LHTH, aerobic performance decreased 1.7% in POST1, but showed an amazing increase in POST2 (15.4 s reduction in the 3000 m test, 2.8%). Regarding anaerobic parameters, athletes showed a reduction in velocity, force and power in POST1, but velocity and power returned to their initial conditions in POST2. In addition, all participants had higher hemoglobin (Hb) values at the end of LHTH (30 days), but at POST2 these results were close to those of PRE. The centrality metrics obtained by complex networks (pondered degree, pagerank and betweenness) in the PRE and POST2 scenarios highlighted hemoglobin, hematocrit (Hct) and minimum force, velocity and power, suggesting these variables on the way to increasing endurance performance. The Jaccard's distance metrics showed dissimilarity between the PRE and POST2 graphs, and Hb and Hct as more prominent nodes for all centrality metrics. These results indicate that adaptive process from LHTH was highlighted by the complex networks, which can help understanding the better aerobic performance at low altitude after 16 days in Paralympic athletes., (© 2022. The Author(s).)

Dark caves lacking primary productivity can expose subterranean animals to hypoxia. We used the surface-dwelling (surface fish) and cave-dwelling (cavefish) morphs of Astyanax mexicanus as a model for understanding the mechanisms of hypoxia tolerance in the cave environment. Primitive hematopoiesis, which is restricted to the posterior lateral mesoderm in other teleosts, also occurs in the anterior lateral mesoderm in Astyanax , potentially pre-adapting surface fish for hypoxic cave colonization. Cavefish have enlarged both hematopoietic domains and develop more erythrocytes than surface fish, which are required for normal development in both morphs. Laboratory-induced hypoxia suppresses growth in surface fish but not in cavefish. Both morphs respond to hypoxia by overexpressing hypoxia-inducible factor 1 ( hif1 ) pathway genes, and some hif1 genes are constitutively upregulated in normoxic cavefish to similar levels as in hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive hif1 gene overexpression., Competing Interests: Cv, WJ No competing interests declared, (© 2022, van der Weele and Jeffery.)

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33-36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week ( p = 0.03) while a non-significant difference was observed after 4 weeks ( p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.

Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT predicts both occurrence and magnitude of potential hypoxemic events 30 minutes in the future, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond., Competing Interests: The authors have declared that no competing interests exist.

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.