Prolonged Intradialytic Hypoxemia Is Associated With Functional Disturbances in Erythrocytes.
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ABSTRACT:
SUBMITTER: Hartzell S
PROVIDER: S-EPMC8484120 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Prolonged Intradialytic Hypoxemia Is Associated With Functional Disturbances in Erythrocytes.
Hartzell Susan S Haverly Meredith M Farouk Samira S Kuntsevich Viktoriya V Cantarelli Chiara C Cravedi Paolo P
Kidney international reports 20210712 10
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Project description:Background and objectivesIntradialytic hypoxemia has been recognized for decades, but its associations with outcomes have not yet been assessed in a large patient cohort.Design, setting, participants, & measurementsOur retrospective cohort study was conducted between January of 2012 and January of 2015. We recorded blood oxygen saturation every minute during hemodialysis in patients with arteriovenous access. A 6-month baseline period with at least 10 treatments with oxygen saturation measurements preceded a 12-month follow-up. Patients were stratified by the presence or absence of prolonged intradialytic hypoxemia defined as oxygen saturation <90% for at least one third of the treatment time. Demographic, laboratory, and treatment data and hospitalization and mortality rates were compared between the groups. Multivariate Cox regression analysis was used to assess baseline predictors of all-cause mortality during follow-up.ResultsIn total, 100 (10%) of 983 patients had prolonged intradialytic hypoxemia. These patients were older (+3.6 years; 95% confidence interval, 0.8 to 6.3), had longer dialysis vintage (+1.2 years; 95% confidence interval, 0.3 to 2.1), and had higher prevalence of congestive heart failure (+10.8%; 95% confidence interval, 1.6 to 20.7) and chronic obstructive pulmonary disease (+13%; 95% confidence interval, 5 to 21.2). They also resembled an inflammatory phenotype, with lower serum albumin levels (-0.1 g/dl; 95% confidence interval, -0.2 to 0) and higher neutrophil-to-lymphocyte ratios (+1; 95% confidence interval, 0.5 to 1.6). They had lower hemoglobin levels (-0.2 g/dl; 95% confidence interval, -0.4 to 0) and required more erythropoietin (+1374 U per hemodialysis treatment; 95% confidence interval, 343 to 2405). During follow-up, all-cause hospitalization (1113 hospitalizations; univariate hazard ratio, 1.46; 95% confidence interval, 1.22 to 1.73) and mortality (89 deaths; adjusted hazard ratio, 1.98; 95% confidence interval, 1.14 to 3.43) were higher in patients with prolonged intradialytic hypoxemia.ConclusionsProlonged intradialytic hypoxemia was associated with laboratory indicators of inflammation, higher erythropoietin requirements, and higher all-cause hospitalization and mortality.
| S-EPMC4822673 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following.MethodsIn this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).ResultsFive hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021).InterpretationSurvivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.
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Project description:Background:The pathophysiology of a paradoxical systolic blood pressure (SBP) rise during hemodialysis (HD) is not yet fully understood. Recent research indicated that 10% of chronic HD patients suffer from prolonged intradialytic hypoxemia. Since hypoxemia induces a sympathetic response we entertained the hypothesis that peridialytic SBP change is associated with arterial oxygen saturation (SaO2). Methods:We retrospectively analyzed intradialytic SaO2 and peridialytic SBP change in chronic HD patients with arteriovenous vascular access. Patients were followed for 6 months. We defined persistent intradialytic hypertension (piHTN) as average peridialytic SBP increase ≥10 mmHg over 6 months. Linear mixed effects (LME) models were used to explore associations between peridialytic SBP change and intradialytic SaO2 in univariate and adjusted analyses. Results:We assessed 982 patients (29 872 HD treatments; 59% males; 53% whites). Pre-dialysis SBP was 146.7 ± 26.5 mmHg and decreased on average by 10.1 ± 24.5 mmHg. Fifty-three (5.7%) patients had piHTN. piHTN patients had lower intradialytic SaO2, body weight and interdialytic weight gain. LME models revealed that with every percentage point lower mean SaO2, the peridialytic SBP change increased by 0.46 mmHg (P < 0.001). This finding was corroborated in multivariate analyses. Conclusion:We observed an inverse relationship between intradialytic SaO2 and the blood pressure response to HD. These findings support the notion that hypoxemia activates mechanisms that partially blunt the intradialytic blood pressure decline, possibly by sympathetic activation and endothelin-1 secretion. To further explore that hypothesis, specifically designed prospective studies are required.
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Project description:AIMS:Among patients with neuromyelitis optica spectrum disorder (NMOSD), fatigue is commonly complained about and is one of the most debilitating symptoms. This study aimed to investigate the incidence of fatigue and explore impacting factors attributed to fatigue in NMOSD. METHODS:Thirty-three patients with NMOSD and twenty matched healthy controls were enrolled. A battery of self-reported questionnaires was conducted to assess quality of sleep, daytime sleepiness, fatigue, depression, and level of activity of daily life. The structure of sleep was assessed by polysomnography with blood oxygen saturation monitored by noninvasive pulse oximeter. Brain and spinal cord lesions were evaluated by MRIs. RESULTS:Fatigue was more severe and more prevalent among the patients with NMOSD compared with controls (fatigue score which ranges from 0 to 11 with higher scores indicating more severe fatigue: 6.4 ± 0.6 vs. 3.8 ± 0.4, P = 0.002; incidence, 64% vs. 35%, P = 0.043), and it was negatively associated with daily activity level (r = 0.455, P = 0.008). The patients with fatigue had higher Pittsburgh Sleep Quality Index score, higher Epworth Sleepiness Scale score, lower blood oxygen state, and higher depression score than patients without fatigue; blood oxygen was especially negatively correlated with fatigue (nadir SpO2 , r = -0.558, P = 0.001; mean SpO2 , r = -0.457, P = 0.007); depression was also positively correlated with fatigue (r = 0.599, P < 0.001). CONCLUSION:Patients with NMOSD experienced significant fatigue, which had an obvious impact on their daily activity. Fatigue in these patients was related to hypoxemia, sleep disturbances, and depression.
| S-EPMC4478121 | biostudies-literature
Project description:Community-acquired respiratory distress syndrome (CARDS) toxin is a unique Mycoplasma pneumoniae virulence factor. Molecular assays targeting this toxin are more sensitive than existing diagnostics, but these assays have not been used to investigate the role of M pneumoniae as a nosocomial infection in critical illness. We sought to determine the incidence of M pneumoniae among mechanically ventilated subjects using these novel assays and to investigate the impact of this pathogen on pulmonary outcomes.We conducted a prospective observational study enrolling subjects with suspected ventilator-associated pneumonia (VAP) undergoing BAL in the surgical trauma ICU at a level I trauma center. Lavage fluid and serum samples were tested for M pneumoniae using assays to detect CARDS toxin gene sequences, protein, or antitoxin antibodies.We collected samples from 37 subjects, with 41% (15 of 37) testing positive using these assays. The positive and negative groups did not differ significantly in baseline demographic characteristics, including age, sex, injury severity, or number of ventilator days before bronchoscopy. The positive group had significantly fewer ventilator-free days (P = .04) and lower average oxygenation (P = .02). These differences were most pronounced among subjects with ARDS.Evidence is provided that M pneumoniae is present in a substantial number of subjects with suspected VAP. Subjects testing positive experience a significantly longer ventilator course and worse oxygenation compared with subjects testing negative.
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Project description:Attempts to apply artificial nano/micromotors for diverse biomedical applications have inspired a variety of strategies for designing motors with diverse propulsion mechanisms and functions. However, existing artificial motors are made exclusively of synthetic materials, which are subject to serious immune attack and clearance upon entering the bloodstream. Herein we report an elegant approach that turns natural red blood cells (RBCs) into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into the RBCs, where their asymmetric distribution within the cells results in a net magnetization, thus enabling magnetic alignment and guidance under acoustic propulsion. The RBC motors display efficient guided and prolonged propulsion in various biological fluids, including undiluted whole blood. The stability and functionality of the RBC motors, as well as the tolerability of regular RBCs to the ultrasound operation, are carefully examined. Since the RBC motors preserve the biological and structural features of regular RBCs, these motors possess a wide range of antigenic, transport, and mechanical properties that common synthetic motors cannot achieve and thus hold considerable promise for a number of practical biomedical uses.
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Project description:Red blood cells (RBCs) attract significant interest as carriers of biomolecules, drugs, and nanoparticles. In this regard, versatile technologies to attach molecules and ligands to the RBC surface are of great importance. Reported here is a fast and efficient surface painting strategy to attach ligands to the surface of RBCs, and the factors that control the stability and circulation properties of the modified RBCs in vivo. Distearoyl phosphatidylethanolamine anchor-conjugated immunoglobulin (IgG) efficiently incorporates in the RBC membrane following 15-30 min incubation. The optimized RBCs show prolonged circulation in vivo (70% of the injected dose after 48 h) and efficient retention of IgG in the membrane with terminal half-life of 73 h. The IgG construct is gradually lost from the RBCs mainly due to the transfer to plasma components, liver endothelial cells, and Kupffer cells. The ligand retention efficiency is partially dictated by ligand type, anchor type, and ligand concentration in the membrane, while RBC half-life is determined by initial concentration of the ligand in the membrane and presence of PEG linker between the ligand and the anchor. This work provides important guidance for non-covalent surface painting of RBCs as well as other types of blood borne cells for in vivo therapeutic and targeting applications.
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Project description:Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
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Project description:Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5; leucine-rich, glioma-inactivated protein 1 (LGI1); contactin-associated protein 2 (CASPR2); N-methyl-D-aspartate (NMDA)-receptor; Ma2; dipeptidyl-peptidase-like protein-6 (DPPX); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R); anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu); anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri); gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R); metabotropic glutamate receptor 5 (mGluR5); and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.
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Project description:Hemodialysis (HD) patients frequently experience cognitive and physical impairments due to various factors, including age, comorbidities, and the demanding nature of the treatment. This study explores the impact of a 12 week integrated cognitive and physical training program on the functional capacity of patients on HD. A single blind, randomized controlled trial was conducted with 44 patients on HD. Participants were divided into an experimental (EXP) group that received a combined intervention of intradialytic cycling and cognitive training, and a control (CON) group receiving standard HD treatment. The Trail Making Test (TMT), Timed Up and Go (TUG) test, and TUG dual task test (TUG-dual) were conducted before and after the intervention. The EXP group demonstrated significant improvements in cognitive function, as evidenced by decreased TMT completion times (TMTA: -3.6 s, P = 0.006; TMTB: -14.0 s, P < 0.001; TMTB - TMTA: -10.4 s, P = 0.004). In contrast, the CON group experienced a significant decline in TMTA and TMTB. In addition, the EXP group exhibited enhanced mobility, with reduced TUG completion times (-0.8 s, P < 0.001) and improved cognitive motor performance in the TUG-dual (-1.0 s, P < 0.001), whereas the CON group showed no significant changes. This study demonstrates that a 12 week combined cognitive and physical training program during HD sessions significantly enhances cognitive function and mobility in patients on HD. These findings suggest that integrated interventions can mitigate functional declines in this population and improve their overall quality of life. Further research with larger samples and active control groups is warranted to confirm and expand upon these promising results.
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