BACKGROUND A recent clinical study of patients with inappropriate sinus tachycardia reported that autoantibodies to β-adrenergic receptors (β2ARs) could act as agonists to induce atrial arrhythmias. OBJECTIVE To test the hypothesis that activating autoantibodies to the β2AR in the rabbit atrium are arrhythmogenic. METHODS Five New Zealand white rabbits were immunized with a β2AR second extracellular loop peptide to raise β2AR antibody titers. A catheter-based electrophysiologic study was performed on anesthetized rabbits before and after immunization. Arrhythmia occurrence was determined in response to burst pacing before and after the infusion of acetylcholine in incremental concentrations of 10 μM, 100 μM, and 1 mM at 1 mL/min. RESULTS In the preimmune studies when β2AR antibody titers were undetectable, of a total of 20 events, only 3 episodes of nonsustained (<10 seconds) atrial arrhythmias were induced. In the postimmune studies when β2AR antibody titers ranged from 1:160,000 to 1:1.28 million, burst pacing induced 10 episodes of nonsustained or sustained (≥10 seconds) arrhythmias in 20 events (P = .04 vs preimmune; χ2 and Fisher exact test). Taking into account only the sustained arrhythmias, there were 6 episodes in 20 events in the postimmune studies compared with 0 episodes in 20 events in the preimmune studies (P = .02). Immunized rabbits demonstrated immunoglobulin G deposition in the atria, and their sera induced significant activation of β2AR in transfected cells in vitro compared to the preimmune sera. CONCLUSIONS Enhanced autoantibody activation of β2AR in the rabbit atrium leads to atrial arrhythmias mainly in the form of sustained atrial tachycardia.

To assess the association between low serum creatinine (SCr) value at admission and the risk of respiratory failure requiring mechanical ventilation in hospitalized patients. A retrospective cohort study was conducted at a tertiary referral hospital. All hospitalized adult patients from 2011 through 2013 who had an admission SCr value were included in this study. Patients who were mechanically ventilated at the time of admission were excluded. Admission creatinine was stratified into 7 groups: ≤0.4, 0.5–0.6, 0.7–0.8, 0.9–1.0, 1.1–1.2, 1.3–1.4, and ≥1.5 mg/dL. The primary outcome was the occurrence of respiratory failure requiring mechanical ventilation during hospitalization. Logistic regression analysis was used to assess the independent risk of respiratory failure based on various admission SCr, using SCr of 0.7–0.8 mg/dL as the reference group in the analysis of all patients and female subgroup and of 0.9–1.0 mg/dL in analysis of male subgroup. A total of 67,045 eligible patients, with the mean admission SCr of 1.0 ± 0.4 mg/dL, were studied. Of these patients, 799 (1.1%) had admission SCr of ≤0.4 mg/dL, and 2886 (4.3%) developed respiratory failure requiring mechanical ventilation during hospitalization. The U-curve relationship between admission SCr and respiratory failure during hospitalization was observed, with the nadir incidence of in-hospital respiratory failure in SCr of 0.7–0.8 mg/dL and increased in-hospital respiratory failure associated with both reduced and elevated admission SCr. After adjustment for confounders, very low admission SCr of ≤0.4 mg/dL was significantly associated with increased in-hospital respiratory failure (OR 3.11; 95% CI 2.33–4.17), exceeding the risk related to markedly elevated admission SCr of ≥1.5 mg/dL (OR 1.61; 95% CI 1.39–1.85). The association remained significant in the subgroup analysis of male and female patients. Low SCr value at admission is independently associated with increased in-hospital respiratory failure requiring mechanical ventilation in hospitalized patients.

Background and objectivesThis study aimed to investigate the association between in-hospital trajectories of serum sodium and risk of in-hospital and 1-year mortality in patients in hospital.Design, setting, participants, & measurementsThis is a single-center cohort study. All adult patients who were hospitalized from years 2011 through 2013 who had available admission serum sodium and at least three serum sodium measurements during hospitalization were included. The trend of serum sodium during hospitalization was analyzed using group-based trajectory modeling; the five main trajectories were grouped as follows: (1) stable normonatremia, (2) uncorrected hyponatremia, (3) borderline high serum sodium, (4) corrected hyponatremia, and (5) fluctuating serum sodium. The outcome of interest was in-hospital mortality and 1-year mortality. Stable normonatremia was used as the reference group for outcome comparison.ResultsA total of 43,539 patients were analyzed. Of these, 47% had stable normonatremia, 15% had uncorrected hyponatremia, 31% had borderline high serum sodium, 3% had corrected hyponatremia, and 5% had fluctuating serum sodium trajectory. In adjusted analysis, there was a higher in-hospital mortality among those with uncorrected hyponatremia (odds ratio [OR], 1.33; 95% CI, 1.06 to 1.67), borderline high serum sodium (OR, 1.66; 95% CI, 1.38 to 2.00), corrected hyponatremia (OR, 1.50; 95% CI, 1.02 to 2.20), and fluctuating serum sodium (OR, 4.61; 95% CI, 3.61 to 5.88), compared with those with the normonatremia trajectory. One-year mortality was higher among those with uncorrected hyponatremia (hazard ratio [HR], 1.28; 95% CI, 1.19 to 1.38), borderline high serum sodium (HR, 1.18; 95% CI, 1.11 to 1.26), corrected hyponatremia (HR, 1.24; 95% CI, 1.08 to 1.42), and fluctuating serum sodium (HR, 2.10; 95% CI, 1.89 to 2.33) compared with those with the normonatremia trajectory.ConclusionsMore than half of patients who had been hospitalized had an abnormal serum sodium trajectory during hospitalization. This study demonstrated that not only the absolute serum sodium levels but also their in-hospital trajectories were significantly associated with in-hospital and 1-year mortality. The highest in-hospital and 1-year mortality risk was associated with the fluctuating serum sodium trajectory.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_03_25_CJN.12281019.mp3

Background Fluctuations in serum phosphate levels increased mortality in end-stage renal disease patients. However, the impacts of serum phosphate changes in hospitalized patients remain unclear. This study aimed to test the hypothesis that serum phosphate changes during hospitalization were associated with in-hospital mortality. Methods We included all adult hospitalized patients from January 2009 to December 2013 that had at least two serum phosphate measurements during their hospitalization. We categorized in-hospital serum phosphate changes, defined as the absolute difference between the maximum and minimum serum phosphate, into 5 groups: 0–0.6, 0.7–1.3, 1.4–2.0, 2.1–2.7, ≥2.8 mg/dL. Using serum phosphate change group of 0–0.6 mg/dL as the reference group, the adjusted odds ratio of in-hospital mortality for various serum phosphate change groups was obtained by multivariable logistic regression analysis. Results A total of 28,149 patients were studied. The in-hospital mortality in patients with serum phosphate changes of 0–0.6, 0.7–1.3, 1.4–2.0, 2.1–2.7, ≥2.8 mg/dL was 1.5, 2.0, 3.1, 4.4, and 10.7%, respectively (p < 0.001). When adjusted for confounding factors, larger serum phosphate changes were associated with progressively increased in-hospital mortality with odds ratios of 1.35 (95% 1.04–1.74) in 0.7–1.3 mg/dL, 1.98 (95% CI 1.53–2.55) in 1.4–2.0 mg/dL, 2.68 (95% CI 2.07–3.48) in 2.1–2.7 mg/dL, and 5.04 (95% CI 3.94–6.45) in ≥2.8 mg/dL compared to serum phosphate change group of 0–0.6 mg/dL. A similar result was noted when we further adjusted for either the admission or mean serum phosphate during hospitalization. Conclusion Greater serum phosphate changes were progressively associated with increased in-hospital mortality.