Clinical efficacy and safety of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension.

OBJECTIVE: This study aimed to investigate the safety, tolerability, and efficacy of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension. METHODS: This retrospective cohort study included clinical data from five children and six young adults with pulmonary arterial hypertension receiving selexipag as add-on therapy or as a transition from beraprost sodium or epoprostenol infusion therapy. Clinical efficacy was evaluated by measuring improvement in clinical variables from baseline, including hemodynamic parameters. RESULTS: Of the 11 patients, 6 were switched from beraprost sodium to selexipag and one paediatric patient transitioned from epoprostenol to selexipag. The median maintenance dose of selexipag in children was 80 µg/kg/day. In nine patients undergoing repeat catheterisation, statistically significant improvements were observed after the initiation of selexipag in terms of mean pulmonary arterial pressure (p < 0.01), pulmonary vascular resistance index (p < 0.05), and cardiac index (p < 0.01). None of the patients had clinical worsening after selexipag during follow-up, but one young adult patient discontinued treatment due to severe headache. The most common side effect profiles were headache, nausea, abdominal pain, jaw pain, myalgia, and diarrhoea. CONCLUSIONS: Selexipag may have a favourable safety profile and potential efficacy in children and young adults with pulmonary arterial hypertension.

Clinical differences between children and adults with idiopathic and heritable pulmonary arterial hypertension.

BACKGROUND: Although previous studies have demonstrated that paediatric pulmonary arterial hypertension remains distinct from that in adults, there are limited studies evaluating a direct comparison between children and adults. The aim of this head-to-head comparison study was to compare the gender, haemodynamic parameters, and prognosis between paediatric and adult pulmonary arterial hypertension. METHODS AND RESULTS: We retrospectively assessed the clinical differences in 40 childhood-onset (under 20 years old) patients and 40 adult-onset patients with idiopathic and heritable pulmonary arterial hypertension who were followed up at two centres. There was no female predominance among patients with childhood-onset pulmonary arterial hypertension (child female: 42.5%, adult female: 80%). The percent of New York Heart Association functional class IV in adult-onset pulmonary arterial hypertension tended to be higher than those in childhood-onset pulmonary arterial hypertension (22.5 and 10%, respectively), although children had worse haemodynamic parameters at diagnosis (mean pulmonary artery pressure (children versus adults); median 65 mmHg versus 49 mmHg, p < 0.001). There was no significant difference in the event-free survival rate between the two groups (95% vs. 85%) during the follow-up period (median, 96 months; range, 1-120 months). CONCLUSIONS: Although paediatric pulmonary arterial hypertension patients had worse haemodynamic parameters at diagnosis than adults, children survived as long as adults with appropriate therapeutic strategies.

Polarization-insensitive local-oscillator-carrier loopback modulation for a cost-effective and high-port-count wavelength-routing optical switch.

A wavelength-routing optical switch uses a wavelength-tunable laser at each input port, and this transmitter implements output port selection by tuning the wavelength that is associated with each output port. With coherent transmission, loopback modulation of a local oscillator (LO) carrier generated at the output port can eliminate the need for a wavelength-tunable laser. However, loopback modulation can be unstable since the power fluctuates because fiber traversal by the light creates polarization rotation. Here, we propose a simple polarization-alignment circuit and verify its effectiveness in creating a high-port-count optical switch system. The proposed circuit consists of passive components and aligns the polarization state of the supplied LO carrier to be linearly polarized along the x-direction of a TE-input dual-polarization (DP) IQ modulator. The circuit is shown to yield stable modulation with Q-variation of less than 0.8 dB, regardless of any birefringence along the transmission path. The proposal's effectiveness is verified in optical switch system experiments with DP-QPSK signals; 1,856 × 1,856 switch scale is achieved with loopback modulation.

A case of squamous cell lung cancer treated with anamorelin in combination with a multidisciplinary collaborative approach for treating cancer cachexia.

Anamorelin (ANA) is approved for treating cancer cachexia (CCX) in Japan. We report the case of a 69-year-old man with stage IVB squamous cell lung cancer complicated by CCX, having a 13.6% weight loss in 6 months. After chemotherapy was initiated, his weight was further reduced. Therefore, we started ANA combined with a treatment approach by a multidisciplinary collaboration, including nutritionists and physical therapists. After initiation of ANA, the body weight, appetite, psoas muscle index, and physical functions rapidly improved during chemotherapy. ANA administration combined with a multidisciplinary collaboration approach can be an effective supportive therapy against CCX during chemotherapy.

A case of renal cell carcinoma with late recurrence in the bilateral hilar lymph nodes twenty years after surgery.

Renal cell carcinoma (RCC) is a common malignancy with a high recurrence rate. However, brain and bilateral hilar lymph node (BHL) relapse is rare. A 65-year-old man with a chief complaint of hemosputum visited the primary care clinic. Computed tomography revealed BHL enlargement. Histopathological examination of biopsy specimens from the left lingular bronchus revealed RCC. This finding was similar to that of a left nephrectomy specimen of RCC observed 20 years ago. If patients have a medical history of RCC, physicians should consider the possibility of RCC recurrence, regardless of the number of years relapsed postoperatively.

Design and verification of a LO bank enabled by fixed-wavelength lasers and fast tunable silicon ring filters for creating large scale optical switches.

The fast and widely tunable wavelength bank is a key enabler in creating wavelength-routing optical switches that do not use fast wavelength tunable lasers. A cost-effective design criterion needs to be developed before it can be applied to intra data center networks. In this paper, we develop a systematic method for designing a wavelength bank that yields high port-count and fast wavelength-routing optical switches for intra data center application. The wavelength bank is created with fixed-wavelength laser sources and wavelength-tunable filters with rapid wavelength selectivity. To optimize the optical switching system that uses the wavelength bank for supplying local oscillator (LO) lights for coherent detection, various parameters are analyzed, including effective bandwidth, laser output power, loss distribution, splitter port count, and optical amplifier gain. We carry out numerical simulations for optimizing the tradeoff between system performance and cost. To verify the designed wavelength bank, a silicon ring filter is newly fabricated with an average fiber-to-fiber insertion loss of 5.3 dB over a 22-nm bandwidth. Using 256-Gb/s DP-QPSK signals, experiments demonstrate a 1,024×1,024 optical switch that uses a fabricated silicon ring filter. The effectiveness of the scalable and fast-tunable LO bank is verified by achieving 262.1-Tb/s switch throughput with switching time under 18 µs.

Medicine at mass gatherings: current progress of preparedness of emergency medical services and disaster medical response during 2020 Tokyo Olympic and Paralympic Games from the perspective of the Academic Consortium (AC2020).

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium.

SiN/Si double-layer platform for ultralow-crosstalk multiport optical switches.

We experimentally demonstrate a double-layer platform of silicon nitride and silicon for ultralow-crosstalk multiport optical switches. By using a silicon nitride overpass with a large gap of 1.5 µm, we achieve a crosstalk of less than -50 dB and -45 dB almost entirely in the C-band for 4 × 4 and 16 × 16 switches, respectively. To demonstrate the scalability of the platform, we also measured a 32 × 32 passive test device and show that a worst-case crosstalk of less than -50 dB is feasible with appropriate gate switches.

Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis.

BACKGROUND: Supravalvular aortic stenosis (SVAS) is one of the congenital cardiovascular diseases characterized by stenosis of the aorta. The stenotic lesions occur anywhere above the aortic valve in the aortic tree as well as pulmonary arteries and eventually leads to circulatory failure. The disease gene has been identified on the elastin gene (ELN) and two types of SVAS have been categorized; a familial type and an isolated type with the de novo mutation. METHODS: Fluorescent In situ hybridization (FISH) analysis and gene sequencing were performed in a two-generation family in which severe form of SVAS was diagnosed. RESULTS: None of the patients tested showed microdeletion of ELN, LIMK1, and D7S613. A novel nonsense mutation of ELN (c.160G>T (p.(Gly54*)), RNA not analyzed) was found in exon 3 in three members; two of them died suddenly due to rapid progression of SVAS with possible arrhythmia in early infancy. A point mutation in the 5' untranslated region, which was previously suggested to be associated with SVAS, did not co-segregate with the SVAS phenotype and found to be SNPs. CONCLUSION: Our report shows a broad spectrum of clinical features in family members sharing the identical mutations, suggesting a potential contribution of modifier gene(s) or interactions with environmental factors.

Changes in cardiac function after renal transplantation in children: Significance of pre-transplantation left ventricular hypertrophy.

LVH is a significant risk factor for the development of cardiovascular morbidity. However, few studies have evaluated the changes in cardiac function that occur in pediatric patients with ESRD undergoing RTx. Therefore, we assessed the changes in parameters associated with LVH in children within the first year after RTx. We retrospectively evaluated patients aged < 18 years who underwent initial RTx from April 2014 to December 2016. The patients were divided into 2 groups according to the presence of LVH before RTx. Clinical, biochemical, and echocardiographic parameters including the LVMI before and 1 year after RTx were evaluated in both groups. Twenty-six patients were included in this study. Seven of the 26 patients had LVH before RTx. Among the echocardiographic parameters, the LVMI was significantly improved 1 year after RTx in the initial LVH group (57.79 ± 11.86 vs 42.20 ± 6.03 g/cm2.7 , P = .018), while no change was observed in the initial non-LVH group (32.66 ± 7.52 vs 35.17 ± 12.86 g/cm2.7 , P = .376). Improvement of the ejection fraction was also observed only in the initial LVH group (66.5% ± 5.3% vs 72.2% ± 5.2%, P = .042). Children who had LVH before RTx showed significant improvements in the LVMI and ejection fraction even within 1 year after RTx. To minimize aggravation of cardiac function, early RTx should be considered for patients with LVH.

Clinical Effects of Syncope on Disease Severity and Adverse Outcomes in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension.

Syncope is more common in children with idiopathic pulmonary arterial hypertension (PAH) than in adults with PAH. Although syncope is associated with a poor prognosis in adult PAH, the clinical effects of syncopal events on disease severity and outcome in children have not been carefully investigated. This study assessed the prevalence of syncope in pediatric PAH and examined its clinical, hemodynamic, and prognostic importance. This retrospective study assessed clinical data, including syncope status, from 78 children (37 girls) with idiopathic and heritable PAH (median age at diagnosis, 11 years). Patients were classified as syncopal or non-syncopal, and clinical data from the two groups were compared. The primary outcome was a composite of lung transplantation and cardiac mortality. Overall, 31 (38%) children had a history of syncope at presentation. Median age at diagnosis, sex ratio, brain natriuretic peptide level, and 6-min walk distance at diagnosis did not differ between groups. The hemodynamic parameters of initial right heart catheterization were similar between the syncope and non-syncope group (mean pulmonary artery pressure, 67 versus 71 mm Hg; cardiac index, 2.9 versus 2.9 l/min/m2, respectively). There was not significantly difference in event-free survival rate between two groups. Although syncopal events are common in children with PAH, our findings suggest that syncope may not be correlated with disease severity or outcome in pediatric PAH.

Correction to: Clinical Effects of Syncope on Disease Severity and Adverse Outcomes in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension.

The original version of this article unfortunately contained a mistake in the author name. The co-author name should be Hiroyuki Matsuura instead of Horoyuki Matsuura. The original article has been corrected.

Clinical Impact of Main Pulmonary Artery Dilatation on Outcome in Pediatric Idiopathic and Heritable Pulmonary Arterial Hypertension.

BACKGROUND: Few studies have investigated the clinical impact of pulmonary artery (PA) dilatation on outcomes in pediatric pulmonary arterial hypertension (PAH).Methods and Results:This study investigated the clinical outcomes of idiopathic or heritable PAH in 66 children aged <18 years at diagnosis. Main PA/thorax (MPA/T) ratio was measured on chest radiography in PAH patients. Patients were divided into 2 groups based on MPA/T ratio, and compared with a control group of 166 age- and gender-matched healthy children. Group A had higher MPA/T ratio than normal, and group B had normal MPA/T ratio. Composite outcomes included cardiac death, lung transplantation, and hospitalization due to heart failure. Group A consisted of 27 patients and group B, 39 patients. At diagnosis, group A had significantly higher brain natriuretic peptide (BNP), cardiothoracic ratio, PA pressure, and pulmonary vascular resistance index compared with group B. The number of patients with New York Heart Association (NYHA) functional class III and IV was significantly higher in group A than in group B. Cumulative event-free survival rate was significantly lower in group A. CONCLUSIONS: MPA dilatation correlated with BNP, NYHA functional class, and hemodynamics with regard to disease severity, and may be a potential prognostic factor in pediatric idiopathic and heritable PAH.

Broadband silicon photonics 8 × 8 switch based on double-Mach-Zehnder element switches.

We fabricated and characterized a silicon photonics 8 × 8 strictly non-blocking optical switch based on double-Mach-Zehnder (MZ) element switches. The double-MZ switches, each of which consisted of an intersection and two asymmetric MZ switches, enabled the suppression of crosstalk across a wide wavelength range. The 8 × 8 switch exhibited an average fiber-to-fiber insertion loss of 11.2 dB and -20 dB crosstalk in a bandwidth wider than 30 nm. Furthermore, we constructed an 8 × 8 polarization-diversity switch by using two 8 × 8 switches and demonstrated 32-Gbaud dual-polarization, quadrature-phase-shift-keying, four-channel wavelength-division-multiplexed signal transmission without significant signal degradation.

Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension.

OBJECTIVES: To evaluate the clinical utility of pulmonary artery capacitance index (PACi) in the assessment of disease severity and prognostic value in children with idiopathic and heritable pulmonary arterial hypertension (PAH). STUDY DESIGN: PACi is defined as the ratio of stroke volume index over pulmonary pulse pressure. A retrospective study was performed to compare PACi, brain natriuretic peptide (BNP), 6-minute walk distance, New York Heart association (NYHA) functional class, and adverse outcomes (hospitalization due to heart failure, lung transplantation, and cardiac mortality) in 72 Japanese children (10 ± 3.6 years) with idiopathic and heritable PAH. RESULTS: PACi had significant correlations with pulmonary vascular resistance index (r =-0.73, P < .0001), BNP levels (r = -0.40, P = .0008), and 6-minute walk distance (r = 0.57, P < .05). Statistically significant differences in PACi were observed between NYHA functional class II vs combined III and IV (median; 1.1 vs 0.6 mL/mm Hg/m2, respectively, P < .05). There were 25 of 72 (35%) children who had an adverse event including initiation of hospitalization due to heart failure, lung transplantation, and death. Cumulative event-free survival rate was significantly lower when PACi was <0.85 mL/mm Hg/m2 (log-rank test, P < .0001). CONCLUSIONS: PACi correlated with BNP and NYHA functional class and may serve as a strong prognostic marker in children with idiopathic and heritable PAH.

Cardiac catheterization in children with pulmonary arterial hypertension.

Cardiac catheterization of childhood pulmonary arterial hypertension (PAH) is used to assess the severity of the disease as well as prognosis, selection of the most adequate pulmonary vasodilators, and evaluation of effectiveness. Sudden deterioration of cardiovascular hemodynamics, however, can be easily induced by pain, patient agitation, catheter manipulation, and by vasodilator provocation tests; these could trigger a pulmonary hypertension crisis, vagotony, respiratory distress, and hemoptysis resulting in critical complications, including death. Those patients with New York Heart Association functional class IV are at an especially high risk. It is noteworthy that pulmonary arteriography is a contraindication in patients with PAH. In a review of 7218 adult patients, 76 (1.1%) serious complications, including four deaths, were reported; with regard to the pediatric patients, 29 (10.7%) out of 270 patients with complications, including one with cardiogenic shock requiring cardiopulmonary resuscitation in addition to minor complications, were reported. To prevent serious complications, basic and routine precautions, such as oxygen and concomitant transcutaneous oxygen saturation and electrocardiogram monitoring during transportation to and from the catheter laboratory, are mandatory. Furthermore, the cooperation of experienced physicians and well informed medical staff in addition to meticulous preparation, for example, calculation of prior doses of catecholamine and confirmation of the presence of emergency equipment, is required.