Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r ²×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSV_D: RSV_D= TSV − FSV) and regurgitant fraction (RF: RF = RSV_D/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSV_D (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m²) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.     

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.     

Upcycling of Pharmaceutical Glass into Highly Porous Ceramics: From Foams to Membranes

The present COVID-19 emergency has dramatically increased the demand for pharmaceutical containers, especially vials. End-of-life containers, however, cannot be easily recycled in the manufacturing of new articles. This paper presents some strategies for upcycling of pharmaceutical glass into various porous ceramics. Suspensions of a fine glass powder (70 vol%) are used as a starting material. Highly uniform cellular structures may be easily prepared by vigorous mechanical stirring of partially gelified suspensions with added surfactant, followed by drying and firing at 550–650 °C. Stabilization of the cellular structures at temperatures as low as the glass transition temperature (T_g) of the used glass is facilitated by thermal decomposition of the gel phase, instead of viscous flow sintering of glass. This finding enabled the preparation of glass membranes (∼78 vol% open porosity), by direct firing of hardened suspensions, avoiding any surfactant addition and mechanical stirring. The powders obtained by crushing of hardened suspensions, even in unfired state, may be used as a low-cost sorbent for dye removal.     

Mealtime Regularity Is Associated with Dietary Balance among Preschool Children in Japan—A Study of Lifestyle Changes during the COVID-19 Pandemic

The novel coronavirus-19 (COVID-19) pandemic has considerably impacted children’s lives. The aim of this study was to determine whether the pandemic affected mealtime regularity among preschool children and whether maintaining regular mealtimes or changes in mealtime regularity during the pandemic were related to dietary balance, including chronological relationships. This online cross-sectional survey involving individuals registered with a company that provides meals to children aged 2−6 years was conducted in February 2021. Using a 40-point scale, a healthy diet score (HDS) was developed to evaluate children’s dietary balance. The participants were divided into four groups based on their responses, and multiple regression analyses were performed with the HDS as the dependent variable. Maintaining regular mealtimes was associated with practices such as waking and going to bed earlier, less snacking, and eating breakfast every day. Even after adjusting for basic attributes, lifestyle habits, household circumstances, and other factors, regular mealtimes were still positively correlated with the HDS. These findings indicate that maintaining regular mealtimes is associated with higher HDS scores and better lifestyle habits. Furthermore, as the changed HDS was higher in the group whose mealtimes became regular during the pandemic, adopting regular mealtimes may lead to a more balanced diet.     

Duloxetine-induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone in a Super-elderly Patient

Duloxetine is widely used for pain control and depressive syndromes. One of its potential side effects is syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Duloxetine-induced SIADH causes hyponatremia, which leads to a variety of symptoms and has previously been reported in the elderly. In the present case, we experienced a case of the rapid onset of SIADH in a super-elderly woman receiving low-dose duloxetine. Elderly patients tend to have lower duloxetine doses and an earlier onset than non-elderly patients. When hyponatremia occurs after duloxetine administration, duloxetine-induced SIADH should be considered, especially in high-risk elderly patients, regardless of the duloxetine dose or duration of treatment.     

Erk pathways negatively regulate matrix mineralization

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.