High-Performance Photodetectors Based on Semiconducting Graphene Nanoribbons.

The inherent zero-band gap nature of graphene and its fast photocarrier recombination rate result in poor optical gain and responsivity when graphene is used as the light absorption medium in photodetectors. Here, semiconducting graphene nanoribbons with a direct bandgap of 1.8 eV are synthesized and employed to construct a vertical heterojunction photodetector. At a bias voltage of -5 V, the photodetector exhibits a responsivity of 1052 A/W, outperforming previous graphene-based heterojunction photodetectors by several orders of magnitude. The achieved detectivity of 3.13 × 1013 Jones and response time of 310 µs are also among the best values for graphene-based heterojunction photodetectors reported until date. Furthermore, even under zero bias, the photodetector demonstrates a high responsivity and detectivity of 1.04 A/W and 2.45 × 1012 Jones, respectively. The work shows a great potential of graphene nanoribbon-based photodetection technology.

Animal models of acute exacerbation of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.

DMF-Assisted Radical Cyclization of o-Isocyanodiaryl Ethers via 1,5-Aryl Migration: Construction of 2-Arylbenzoxazoles.

A novel DMF-assisted radical cyclization of o-isocyanodiaryl ethers via 1,5-aryl migration has been developed for the synthesis of a series of 2-arylbenzoxazoles by the FeCl3/TBHP/Et3N catalytic system in DMF. However, N,N-dimethylbenzo[d]thiazole-2-carboxamide and N,N-dimethylbenzo[d]selenazole-2-carboxamide were obtained from the corresponding substrate 2-isocyanophenyl p-methoxyphenyl thioether and 2-isocyanodiphenyl selenoether under the same conditions. A possible mechanism may involve aryl 1,5-migration and DMF-assisted radical cyclization of o-isocyanodiaryl ethers.

Patient empowerment and self-management behaviour of chronic disease patients: A moderated mediation model of self-efficacy and health locus of control.

AIMS: To explore the role of self-efficacy (SE) in the effect of patient empowerment on self-management behaviours among patients with chronic illness and to investigate the moderating effect of three types of health locus of control (HLC) in this moderated mediation model. DESIGN: Cross-sectional design. METHODS: Data were collected in a general tertiary hospital, and a sample of 254 patients was recruited between August and October 2020. The effect of moderation and mediation was tested by the PROCESS macro (Model 4 and Model 8) for SPSS 25.0 by Hayes using 5000 bootstrap samples. RESULTS: Self-efficacy significantly mediated the relationship between patient empowerment and self-management behaviour with a 95% confidence interval excluding zero. The chance HLC demonstrated a moderating effect, and the interaction effect on SE and self-management behaviour was significant. CONCLUSION: Patient empowerment may improve confidence and adherence to self-management among people with chronic illness, and such benefits were conditional on the HLC of patients. IMPACT: This study addresses the relationship between patient empowerment and self-management behaviour in patients with different personality characteristics. This result indicated that classifying the type of HLC may enable the identification of subgroups of patients who may subsequently benefit from patient empowerment. In a patient-centred programme, nurses and other healthcare professionals correctly identifying patients' HLC type and understanding the implications and then providing appropriate health care plans for patients with different health beliefs may be useful to tailor the decision-making process.

Investigation into the effects of leukemia inhibitory factor on the bone repair capacity of BMSCs-loaded BCP scaffolds in the mouse calvarial bone defect model.

Leukemia inhibitory factor (LIF) is known to play a major role in bone physiology. In the present study, we examined the in vitro effects of LIF on osteoblast differentiation of bone marrow stem cells (BMSCs) and explored in vivo effects of LIF on the bone repair capacity of BMSCs-loaded biphasic calcium phosphate (BCP) scaffolds in mouse calvarial bone defect model. The mRNA and protein expression levels in the BMSCs were determined by quantitative real-time PCR and western blot, respectively; the in vitro osteoblast differentiation of the BMSCs was evaluated by using Alizarin Red S staining. The bone volume and bone density in the repaired calvarial bone defect were determined by Micro-CT. Bone regeneration was also histologically evaluated by hematoxylin and eosin staining and Masson's trichrome staining. Hypoxia treatment induced the up-regulation of Lif mRNA and LIF protein in the BMSCs. Lif overexpression up-regulated the mRNA expression levels of osteopontin and Runt-related transcription factor 2, and increased intensity of Alizarin Red S staining in the BMSCs; while Lif silence exerted the opposite effects. The in vivo studies showed that implantation of Lif-overexpressing BMSCs-loaded BCP scaffolds significantly increased the bone volume and bone density at 4 and 8 weeks after transplantation, and promoted the regeneration of bone tissues in the mouse calvarial bone defect at 8 weeks after transplantation when compared to the BMSCs-loaded BCP scaffolds group; while Lif-silencing BMSCs-loaded BCP scaffolds had the opposite effects. The present study for the first time demonstrated that LIF promoted the in vitro osteoblast differentiation of hypoxia-treated BMSCs; and further studies revealed that LIF exerted enhanced effects on the bone repair capacity of BMSCs-load BCP scaffolds in mouse calvarial bone defect model. However, future studies are warranted to determine the detailed mechanisms of LIF in the large-scale bone defect repair.

The effect of dobutamine in sepsis: a propensity score matched analysis.

BACKGROUND: The use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use of dobutamine was associated with decreased hospital mortality in sepsis patients. METHODS: Based on the analysis of MIMIC III public database, we performed a big-data, real world study. According to the use of dobutamine or not, patients were categorized as the dobutamine group or non dobutamine group.We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality. RESULTS: In the present study, after screening 38,605 patients, 2826 patients with sepsis were included. 121 patients were in dobutamine group and 2165 patients were in non dobutamine group. Compared with patients in non-dobutamine group, patients in dobutamine group had a lower MAP, higher HR, higher RR, higher severity of illness scores. 72 of 121 patients (59.5%) in the dobutamine group and 754 of 2165 patients (34.8%) in the non-dobutamine group died in the hospital, which resulted in a significant between-group difference (OR 1.56, 95% CI 1.01-2.40; P = 0.000). For the secondary outcomes, patients in dobutamine group received more MV use, more renal replacement therapy use, had longer ICU stay durations and more cardiac arrhythmias than those in non-dobutamine group. After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistently higher in dobutamine group than that in non-dobutamine group (60.2% vs. 49.4%, OR 1.55, 95% CI 1.01-2.37; P = 0.044). CONCLUSIONS: Among patients with sepsis, our study showed that the use of dobutamine was not associated with decreased hospital mortality. Further large scale, randomized controlled studies are warrented to confirm our findings.

Analysis of Risk Factors in Endoscopic Retrograde Cholangiopancreatography-Related Immediate and Delayed Hemorrhage.

BACKGROUND/AIMS: Hemorrhage is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). However, there is a lack of comparative studies on immediate and delayed hemorrhage. The present study aims to explore the relevant risk factors of immediate and delayed hemorrhage of ERCP and compare the similarities and differences. METHODS: ERCP cases conducted by our hospital between January 2017 and January 2020 were selected for retrospective analysis. Then age, gender, basic disease, laboratory examinations, and other relevant clinical information were collected for the analysis. RESULTS: A total of 1009 ERCP cases were included in the present study. Among these cases, 76 patients were in the immediate hemorrhage group, 28 patients were in the delayed hemorrhage group, and 905 patients were in the non-hemorrhage group. The univariate analysis revealed that choledocholithiasis, pre-cut, and endoscopic papillary sphincterotomy (EST) were risk factors for immediate hemorrhage, while cholangitis, jaundice, coronary heart disease, pre-cut, high postoperative lipase at four hours and amylase at 24 h, high postoperative leukocyte, urea, bilirubin, low postoperative platelet counts and fibrinogen, and prolonged prothrombin time (PT) and thrombin time (TT) were risk factors for delayed hemorrhage. The logistic regression analysis revealed that EST, pre-cut, and activated partial thromboplastin time (APTT) were independent risk factors for immediate hemorrhage, while high amylase at 24 h after ERCP, high postoperative urea, prolonged TT, and coronary heart disease were independent risk factors for delayed hemorrhage. CONCLUSIONS: Pre-cut was a common risk factor for immediate and delayed hemorrhage, while other risk factors were different.

Hepatitis B Vaccination Response in Hemodialysis Patients: The Impact of Dialysis Shift.

BACKGROUND/AIMS: Hepatitis B (HB) vaccination in hemodialysis patients is important as they are at a higher risk of contracting HB. However, hemodialysis patients have a lower HB seroconversion rate than their healthy counterparts. As better sleep has been associated with better seroconversion in healthy populations and early hemodialysis start has been linked to significant sleep-wake disturbances in hemodialysis patients, we examined if hemodialysis treatment start time is associated with HB vaccination response. METHODS: Demographics, standard-of-care clinical, laboratory, and treatment parameters, dialysis shift data, HB antigen status, HB vaccination status, and HB titers were collected from hemodialysis patients in Fresenius clinics from January 2010 to December 2015. Patients in our analysis received 90% of dialysis treatments either before or after 8:30 a.m., were negative for HB antigen, and received a complete series of HB vaccination (Engerix B® or Recombivax HB™). Univariate and multivariate regression models examined whether dialysis start time is a predictor of HB vaccination response. RESULTS: Patients were 65 years old, 57% male, and had a HD vintage of 10 months. Patients whose dialysis treatments started before 8:30 a.m. were more likely to be younger, male, and have a greater dialysis vintage. Patients receiving Engerix B® and starting dialysis before 8:30 a.m. had a significantly higher seroconversion rate compared to patients who started dialysis after 8:30 a.m. Early dialysis start was a significant predictor of seroconversion in univariate and multivariate regression including male gender, but not in multivariate regression including age, neutrophil-to-lymphocyte ratio, and vintage. CONCLUSION: While better sleep following vaccination is associated with seroconversion in the general population, this is not the case in hemodialysis patients after multivariate adjustment. In the context of end-stage kidney disease, early dialysis start is not a significant predictor of HB vaccination response. The association between objectively measured postvaccination sleep duration and seroconversion rate should be investigated.

Extracorporeal membrane oxygenation versus mechanical ventilation alone in adults with severe acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: COVID-19 can lead to acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is considered to be a salvage strategy for severe ARDS. However, the effect of ECMO therapy on severe ARDS remains inconclusive. We aimed to evaluate the effects of ECMO for adults with severe ARDS. METHODS: We searched six databases (EMBASE, Medline, the Cochrane Library, Web of Science, Wanfang databases and CNKI) from inception to May 2020 to screen relevant high-quality observational studies and randomised controlled trials. We used the random effects model for outcome calculation. Trial sequential analysis (TSA), heterogeneity, sensitivity analysis and publication bias were explored. The primary outcome was 90-day mortality. RESULTS: Seven studies (two RCTs and five observational studies) with a total of 867 patients were included. Compared with MV therapy alone, ECMO therapy significantly reduced the mortality at 90 days (based on RCT studies, Risk Ratio [RR] 0.74, 95% confidence Interval (CI) 0.59-0.93, P = .01, I2  = 0%, moderate quality; based on observational studies, RR 0.61, 95% CI 0.46-0.81, P < .001, I2  = 0%, low quality) and at 30 and 60 days. TSA results were consistent with the primary outcome. Furthermore, device-related adverse events were similar between the ECMO group and MV alone group (RR, 2.09; 95% CI, 0.27-16.03, P = .48, I2  = 0%, moderate quality). CONCLUSIONS: This study showed that the ECMO group exhibited a significantly lower mortality rate compared with the MV alone group at 90, 30 and 60 days for severe ARDS patients.

The effect of dobutamine vs milrinone in sepsis: A big data, real-world study.

BACKGROUND: The use of dobutamine in patients with sepsis is questionable. Some studies reported milrinone was used as an alternative inotropic agent. We aim to evaluate whether milrinone is better than dobutamine in patients with sepsis. METHODS: Based on the analysis of MIMIC III public database, we performed a big data, real-world study. According to the use of dobutamine or milrinone, patients were categorised as the dobutamine group or milrinone group. We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality. RESULTS: In this study, after screening 38 605 patients, 235 patients with sepsis were included. One hundred and eighty-three patients were in the dobutamine group and 52 patients were in the milrinone group. For the primary outcome of hospital mortality, there was no significant between-group difference (73/183 in dobutamine group vs 23/52 in milrinone group, OR 0.84, 95% CI 0.45-1.56; P = .574). After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistent with the overall result (50% vs 41.3%, OR 1.42, 95% CI 0.68-2.97; P = .349). For the secondary outcomes, more patients in milrinone group received RRT use (46.2% vs 22.4%, P = .001), had longer length of ICU stay (20.97 ± 22.84 days vs 11.10 ± 11.54 days, P = .004) and hospital stay (26.14 ± 25.13 days vs 14.51 ± 13.11 days, P = .002) than those in dobutamine group. CONCLUSIONS: Compared with dobutamine, the use of milrinone did not decrease hospital mortality in patients with sepsis. Furthermore, milrinone was associated with more RRT therapy, longer length of ICU stay and hospital stay than dobutamine.

Ethical considerations referred to in child health research published in leading nursing journals: 2015-2019.

BACKGROUND: Child health research comprises complex ethical considerations. Understanding the extent to which the ethical process is reported in child health research is needed to improve reporting. AIMS: To identify reportage of ethical considerations in child health research in leading nursing and paediatric journals. METHODS: All child health research published between 2015 and 2019 in 10 leading nursing journals and two paediatric journals were retrieved and critically appraised for the reportage of informed consent and ethical approval. RESULTS: Eight hundred and fifty-one child health research papers were included. Although 544 (79.9%) of the prospective studies mentioned informed consent, only 300 (55.2%) reported that written informed consent was obtained from the participants. Overall, 748 (87.9%) of child health research papers noted obtaining research ethics committee approval. Articles that mentioned financial support were significantly more likely to report informed consent and ethical approval than unfunded studies (all P < 0.001). Prospective studies showed higher rates of reportage of ethical approval compared to retrospective studies (P = 0.027). Rates of child consent (assent) obtained in different age groups of children ranged from 29.6% to 66.3%. CONCLUSION: Despite improvements in the reportage of ethical review and approval processes in child health research, consistent and transparent reports are still lacking.

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements.

RATIONALE & OBJECTIVES: Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements. STUDY DESIGN: Comparative study of 2 diagnostic tests. SETTING & PARTICIPANTS: Prevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured. TESTS COMPARED: During the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V. OUTCOMES: Concordance between the 2 methods of calculating Kt/V. RESULTS: Among 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were-0.63%±7.7% and-0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods. LIMITATIONS: Data were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions. CONCLUSIONS: A new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.

Clinical and predictive value of simplified creatinine index used as muscle mass surrogate in end-stage kidney disease haemodialysis patients-results from the international MONitoring Dialysis Outcome initiative.

BACKGROUND: Protein-energy wasting, muscle mass (MM) loss and sarcopenia are highly prevalent and associated with poor outcome in haemodialysis (HD) patients. Monitoring of MM and/or muscle metabolism in HD patients is of paramount importance for timely detection of muscle loss and to intervene adequately. In this study we assessed the reliability and reproducibility of a simplified creatinine index (SCI) as a surrogate marker of MM and explored its predictive value on outcome. METHOD: We included all in-centre HD patients from 16 European countries with at least one SCI. The baseline period was defined as 30 days before and after the first multifrequency bioimpedance spectroscopy measurement; the subsequent 7 years constituted the follow-up. SCI was calculated by the Canaud equation. Multivariate Cox proportional hazards models were applied to assess the association of SCI with all-cause mortality. Using backward analysis, we explored the trends of SCI before death. Bland-Altman analysis was performed to analyse the agreement between estimated and measured MM. RESULTS: We included 23 495 HD patients; 3662 were incident. Females and older patients have lower baseline SCI. Higher SCI was associated with a lower risk of mortality [hazard ratio 0.81 (95% confidence interval 0.79-0.82)]. SCI decline accelerated ∼5-7 months before death. Lean tissue index (LTI) estimated by SCI was correlated with measured LTI in both sexes (males: R2 = 0.94; females: R2 = 0.92; both P < 0.001). Bland-Altman analysis showed that measured LTI was 4.71 kg/m2 (±2 SD: -12.54-3.12) lower than estimated LTI. CONCLUSION: SCI is a simple, easily obtainable and clinically relevant surrogate marker of MM in HD patients.

Statistical Reporting in Nursing Research: Addressing a Common Error in Reporting of p Values (p = .000).

PURPOSE: The confidence in a study will be reduced due to the incorrect representation of statistical results. However, it is unknown to what extent p values are incorrectly represented in published nursing journals. The study aims to evaluate the articles in 30 nursing journals in terms of the error in reporting of p values (p = .000). DESIGN AND METHODS: This was a bibliometric analysis. All papers published in 10 leading nursing journals (between 2015 and 2019), the 10 bottom nursing journals (2019), and 10 selected key nursing journals (2019) indexed in the Science Citation Index Journal Citation Reports were reviewed to detect errors in reporting of p values (p = .000). RESULTS: A total of 3,788 papers were reviewed. Notably, it was found that 93.3% (28/30) of the nursing journals contained incorrect representation of p values (p = .000). The reporting rate of these journals ranges from 0% to 57.1%, with an overall rate of 12.8% (486/3,788). In addition, the rate of incorrect representation of p values (p = .000) showed no statistically significant difference between different publication years (Χ2 = 4.976, p = .290). However, the rate of reporting was different between study types, journals, and regions (p = .007, p = .020, and p < .001, respectively). CONCLUSIONS: The incorrect representation of p values is common in nursing journals. CLINICAL RELEVANCE: We recommend that both publishers and researchers be responsible for preventing statistical errors in manuscripts. Furthermore, various kinds of statistical training methods should be adopted to ensure that nurses and journal reviewers have enough statistical literacy.

Hypocalcemia-Induced Slowing of Human Sinus Node Pacemaking.

Each heartbeat is initiated by cyclic spontaneous depolarization of cardiomyocytes in the sinus node forming the primary natural pacemaker. In patients with end-stage renal disease undergoing hemodialysis, it was recently shown that the heart rate drops to very low values before they suffer from sudden cardiac death with an unexplained high incidence. We hypothesize that the electrolyte changes commonly occurring in these patients affect sinus node beating rate and could be responsible for severe bradycardia. To test this hypothesis, we extended the Fabbri et al. computational model of human sinus node cells to account for the dynamic intracellular balance of ion concentrations. Using this model, we systematically tested the effect of altered extracellular potassium, calcium, and sodium concentrations. Although sodium changes had negligible (0.15 bpm/mM) and potassium changes mild effects (8 bpm/mM), calcium changes markedly affected the beating rate (46 bpm/mM ionized calcium without autonomic control). This pronounced bradycardic effect of hypocalcemia was mediated primarily by ICaL attenuation due to reduced driving force, particularly during late depolarization. This, in turn, caused secondary reduction of calcium concentration in the intracellular compartments and subsequent attenuation of inward INaCa and reduction of intracellular sodium. Our in silico findings are complemented and substantiated by an empirical database study comprising 22,501 pairs of blood samples and in vivo heart rate measurements in hemodialysis patients and healthy individuals. A reduction of extracellular calcium was correlated with a decrease of heartrate by 9.9 bpm/mM total serum calcium (p < 0.001) with intact autonomic control in the cross-sectional population. In conclusion, we present mechanistic in silico and empirical in vivo data supporting the so far neglected but experimentally testable and potentially important mechanism of hypocalcemia-induced bradycardia and asystole, potentially responsible for the highly increased and so far unexplained risk of sudden cardiac death in the hemodialysis patient population.

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.

BACKGROUND: Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative. METHODS: All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group. RESULTS: We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results. CONCLUSION: Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.

High-flow nasal cannula oxygen therapy versus conventional oxygen therapy in patients after planned extubation: a systematic review and meta-analysis.

BACKGROUND: The effect of high-flow nasal cannula (HFNC) therapy in patients after planned extubation remains inconclusive. We aimed to perform a rigorous and comprehensive systematic meta-analysis to robustly quantify the benefits of HFNC for patients after planned extubation by investigating postextubation respiratory failure and other outcomes. METHOD: We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library from inception to August 2018. Two researchers screened studies and collected the data independently. Randomized controlled trials (RCTs) and crossover studies were included. The main outcome was postextubation respiratory failure. RESULTS: Ten studies (seven RCTs and three crossover studies; HFNC group: 856 patients; Conventional oxygen therapy (COT) group: 852 patients) were included. Compared with COT, HFNC may significantly reduce postextubation respiratory failure (RR, 0.61; 95% CI, 0.41, 0.92; z = 2.38; P = 0.02) and respiratory rates (standardized mean differences (SMD), - 0.70; 95% CI, - 1.16, - 0.25; z = 3.03; P = 0.002) and increase PaO2 (SMD, 0.30; 95% CI, 0.04, 0.56; z = 2.23; P = 0.03). There were no significant differences in reintubation rate, length of ICU and hospital stay, comfort score, PaCO2, mortality in ICU and hospital, and severe adverse events between HFNC and COT group. CONCLUSIONS: Our meta-analysis demonstrated that compared with COT, HFNC may significantly reduce postextubation respiratory failure and respiratory rates, increase PaO2, and be safely administered in patients after planned extubation. Further large-scale, multicenter studies are needed to confirm our results.

Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling.

BACKGROUND: Hypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown. METHODS: In this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model. RESULTS: The peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and µ-CT results showed that CoCl2 treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2 treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect. CONCLUSIONS: The in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.

Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.