Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors...     

Prognostic value of pacing-induced mechanical alternans in patients with mild-to-moderate idiopathic dilated cardiomyopathy in sinus rhythm.

OBJECTIVES: The relation between the occurrence of pacing-induced mechanical alternans and prognosis in patients with mild-to-moderate idiopathic dilated cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The myocardial expression of genes for Ca2+-handling proteins in such patients was also examined. BACKGROUND: Mechanical alternans occurs in some patients with severe heart failure, but the relation between the occurrence of mechanical alternans and prognosis in patients with IDCM has remained unknown. METHODS: Left ventricular (LV) pressure was measured during atrial pacing, and LV endomyocardial biopsy specimens were collected in 36 IDCM patients and 8 controls. Idiopathic dilated cardiomyopathy patients were divided into two groups consisting of 22 individuals who did not develop mechanical alternans at heart rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The patients were followed up for a mean of 3.7 years. RESULTS: There was no significant difference in LV ejection fraction or the plasma concentration of brain natriuretic peptide between groups A and B. The myocardial abundance of ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca2+-ATPase mRNA was significantly lower in group B than in group A or controls. Stepwise multivariate analysis identified pacing-induced mechanical alternans as the strongest predictor of cardiac events. Event-free survival in group A was significantly greater than that in group B. CONCLUSIONS: The occurrence of pacing-induced mechanical alternans is a potentially useful indicator of poor prognosis in patients with mild-to-moderate IDCM in sinus rhythm.     

Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism

Parathyroid hormone (PTH) and its related receptor (PTHR) are essential regulators of calcium homeostasis and bone physiology. PTH activates PTHR by interacting with a ligand-binding site localized within the N-terminal extracellular domain (the N-domain) and the domain comprising the seven transmembrane helices and the connecting extracellular loops (the J-domain). PTH binding triggers a conformational switch in the receptor, leading to receptor activation and subsequent cellular responses. The process of receptor activation occurs rapidly, within approximately 1 s, but the binding event preceding receptor activation is not understood. By recording FRET between tetramethyl-rhodamine in PTH(1-34) and GFP in the N-domain of the receptor, we measured the binding event in real time in living cells. We show that the association time course between PTH(1-34) and PTHR involves a two-step binding process where the agonist initially binds the receptor with a fast time constant (tau approximately 140 ms) and then with slower kinetics (tau approximately 1 s). The fast and slow phases were assigned to hormone association to the receptor N- and J domains, respectively. Our data indicate that the slow binding step to the J-domain coincides with a conformational switch in the receptor, also monitored by FRET between the enhanced cyan fluorescent protein and the enhanced yellow fluorescent protein in the PTHR sensor, PTHR enhanced cyan fluorescent protein/enhanced yellow fluorescent protein (PTHR(CFP/YFP)). These data suggest that the conformational change that switches the receptor into its active state proceeds in a sequential manner, with the first rapid binding step event preceding receptor activation by PTH(1-34).     

Hemangioma located just above the left main coronary artery, in a subject who had cardiac arrest due to ventricular fibrillation, led to a diagnosis of Brugada syndrome

We report the case of a 38-year-old Asian man with a pericardial hemangioma on the left main coronary artery. The patient presented initially at our hospital after cardiopulmonary resuscitation following an episode of ventricular fibrillation (VF). Because of spontaneous coved-type ST segment elevation on the higher intercostal space V1 to V2 in a 12-lead electrocardiogram, documented VF in the absence of structural heart disease, and a family history of sudden death, he was diagnosed with Brugada syndrome. Transesophageal echocardiography showed a smooth-surfaced mass with well-demarcated borders, directly above the left main coronary artery. Computed tomography confirmed the presence of the mass, which showed no enhancement at early phase, but did demonstrate homogenous enhancement at delay phase by contrast material. There were no findings from either the nuclear medicine or the tumor marker investigations which indicated that the mass located just above the main coronary arteries was malignant. Therefore, taken together, these findings suggested that the tumor might be a pericardial hemangioma. The relationship between the location of the hemangioma just above the left main coronary artery and the occurrence of VF was not clear, i.e. whether the presence of the hemangioma caused the stimulation of the left main coronary artery and as a result, led to the spasm of the left main coronary artery and the occurrence of VF. Furthermore, as the tumor did not extend into any of the adjacent structures, such as the coronary arteries or the right ventricular outflow tract, surgical resection was not performed; instead, the patient received a dual chamber implantable cardioverter-defibrillator.     

The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland–Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130–250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.     

Physical therapists’ perceptions and experiences about barriers and facilitators of therapeutic patient-centred relationships during outpatient rehabilitation: a qualitative study

Background

Over recent years there has been a paradigm shift towards a patient-centred biopsychosocial care model in physical therapy. This new paradigm features a growing interest in understanding the contextual factors that influence the patient's experience of disease, pain and recovery. This includes generalized consensus regarding the importance of establishing a therapeutic relationship that is centred on the patient.

Role of Institutional Climate on Underrepresented Faculty Perceptions and Decision Making in Use of Work–Family Policies

The authors examined the institutional challenges that underrepresented minority (URM) faculty perceive in higher education with use of family support workplace policies. Evidence reveals that faculty encounter differences in access to information and explanations of how to use workplace–family statutes. A qualitative study of 58 URM faculty members highlighted five particularly notable themes: (a) faculty perceptions of how the institution views their family caregiving responsibilities, (b) inadequate compensation matters in the utilization of formal policies, (c) informal policies are often inaccessible and invisible, (d) social networks affect the inclusiveness of work–family institutional practices, and (e) fear of being regarded as a “red flag” constrains decisions regarding the use of policies. Given the push in higher education to diversify its faculty ranks, if administrators are to successfully implement diversity, equity, and inclusion and retain URM faculty, institutions need to pay particular attention to how URM faculty experience the academic climate regarding work–family balance.     

Carbon-ion beams induce production of an immune mediator protein,high mobility group box 1, at levels comparable with X-ray irradiation

X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D₁₀, the dose at which 10% of cells survive, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D₁₀ dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D₁₀ dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams.