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This paper explores how what I call 'administrative categories' have been adopted by the Japanese government and experts in autism support and what roles these categories have played in local settings. Since support practices for children and adults with autism began in the 1950s in Japan, the Japanese government and people engaging in autism support have used Japanese-specific administrative categories, instead of relying on a medical concept of autism, such as 'severe moving disabilities' (SMD), 'emotional disturbance', and 'extremely disruptive behavioural disorders' (EDBD). To understand the emergence of these three autism-related administrative categories in Japan, historical materials published from the 1950s to the 1990s by Japanese authors (doctors, psychologists, teachers, educationalists, welfare workers, government officials, and parents) and interview data with 19 leading experts of autism in Japan were collected and analysed thematically. The analysis revealed that the governmental ministries aimed to focus on establishing administrative support by avoiding engaging in aetiological debates among doctors, and to describe the political agenda more vividly. Administrative categories filled the gap between local interests and international medical concepts, enabling the concept of autism to be rooted in Japan's administrative systems. Three roles of administrative categories were identified: i) separation from medicine, ii) describing local problems, and iii) claimsmaking to wider actors and the public. I concluded that looking purely at medical and specifically diagnostic concepts limits our understanding of the formation of practices regarding disabilities, and thus more focus should be placed on categorisation practices outside of medicine. In addition, to the literature on the globalisation of Euro-American psychiatric concepts, this study contributes to our knowledge of a form of locality that has not been central in the exploration of the influence of globalisation on local settings and the relationships between the local and the global., Competing Interests: Declaration of competing interest The author declares that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.)

Revised idiopathic pulmonary fibrosis treatment guidelines were published in 2015, and nintedanib was conditionally recommended. Although diarrhea is reported to be a common major adverse event associated with nintedanib, there have been few reports on detailed endoscopic findings of nintedanib-associated enterocolitis. A 74-year-old woman was diagnosed with idiopathic pulmonary fibrosis 4 years ago in May. She was started on nintedanib (300 mg). Three months later, hepatic dysfunction was observed; therefore, the drug was temporarily discontinued and then resumed at a dose reduction of 200 mg. Five months later, the patient developed diarrhea, and the dose was reduced to 150 mg. However, no effect was noted; hence, colonoscopy was performed. Various inflammatory lesions, such as erythema and erosions, were observed continuously at the rectum, which resembled ulcerative colitis. No improvement was observed 2 months after follow-up colonoscopy, and nintedanib-related enterocolitis was suspected. The dose was further reduced to 100 mg. Since the endoscopic findings of nintedanib-associated enterocolitis are similar to those of ulcerative colitis, it is critical to consider patients with diarrhea who are taking nintedanib as having associated enterocolitis and attempt to reduce or discontinue the drug if diarrhea does not improve with antidiarrheal agents., (© 2023. Japanese Society of Gastroenterology.)

Background: Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches., Methods: A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not., Results: Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor-1 (TTF-1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001)., Conclusions: Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF-1 positivity, could enhance disease control rates and extend survival., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Sarcopenia, characterized by skeletal muscle atrophy and physical inactivity, is a manifestation of chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. The serum creatinine (Cr)/cystatin C (CysC) ratio has been proposed as a marker of sarcopenia, given its correlation with total skeletal muscle mass, and as a prognostic indicator in COPD. This study aimed to evaluate the usefulness of the serum Cr/CysC ratio as a prognostic determinant in these patients., Methods: A total of 124 outpatients with COPD were enrolled in this study. Their serum Cr and CysC levels were measured. Survival time analyses were conducted to compare mortality rates between the low and high serum Cr/CysC ratio groups. Multivariate analysis was performed to investigate the association between various factors., Results: Using a serum Cr/CysC cut-off value of 0.885, the mortality rate (per 1000 person-years) for overall mortality was significantly higher in the low serum Cr/CysC ratio group (69.2 versus 28.6; hazard ratio, 2.47; 95% confidence interval, 1.06-5.79; p < 0.05). Similarly, the mortality rate due to respiratory disease was also higher (37.8 versus 8.2; hazard ratio, 4.68; 95% confidence interval, 1.05-20.9; p < 0.05). Multivariate Cox proportional hazards analysis revealed that serum Cr/CysC was an independent risk factor for respiratory disease mortality, regardless of age and airflow limitations., Conclusions: The serum Cr/CysC ratio could be a valuable clinical parameter for identifying sarcopenia and severe airflow obstruction. The study findings highlight the utility of this ratio as a prognostic predictor in patients with COPD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Several options for second-line therapy are available for patients with advanced non-small cell lung cancer (NSCLC); however, the optimal therapy remains unclear. Docetaxel (DTX) monotherapy and DTX plus ramucirumab (RAM) are the recommended second-line treatment options. However, the efficacy of these treatments remains unsatisfactory. The aim of this study was to identify the clinical characteristics of patients with NSCLC who respond to DTX or DTX + RAM and factors that predict response., Methods: Patients with NSCLC treated with DTX or DTX + RAM after second-line therapy were retrospectively analyzed. Patients were compared with those who responded or did not respond to the post-treatment efficacy assessment., Results: Of 53 patients, 12 (22.6%) had lung cancer that responded to DTX or DTX + RAM therapy (response group). Multivariate analysis identified the absence of immune checkpoint inhibitors (ICIs) in the immediate prior therapy and a reduced dose of DTX after the second cycle as significant independent risk factors predicting nonresponse to DTX and DTX + RAM therapy in patients with NSCLC. The overall survival was significantly longer in the response group compared to the nonresponse group (p = 0.016)., Conclusions: Our results suggest that DTX and DTX + RAM therapies immediately after treatment with ICI-containing regimens as well as continuation of DTX without dose reduction after the second cycle may increase the response rate and prolong survival in patients with NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background and Objectives : Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods : We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results : The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions : Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

Background: Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with programmed death ligand-1 (PD-L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD-L1 expression <50% has not yet been fully elucidated. The aim of this study was to identify the clinical characteristics of NSCLC patients with PD-L1 expression <50% who respond to single-agent ICIs and factors that predict response., Methods: Patients with advanced or recurrent NSCLC with a PD-L1 tumor proportion score (TPS) of 50% or less who received new monotherapy with an ICI between July 2012 and December 2022 were retrospectively analyzed. Patients with response were compared with those without response in the post-treatment response assessment., Results: Among the 37 patients, six (16.2%) NSCLC patients in the response group responded to ICI monotherapy and had a significantly lower body mass index (BMI) (p = 0.003). Significantly more patients in the response group developed immune-related adverse events (irAEs) than in the nonresponse group (p < 0.001). Multivariate analysis identified high BMI as a significant independent risk factor predicting nonresponse to ICI monotherapy in NSCLC patients with PD-L1 < 50%., Conclusions: Among NSCLC patients with PD-L1 < 50%, those with a higher BMI were more likely to be nonresponders to ICI monotherapy. In addition, the group that responded to ICI monotherapy may have been at higher risk of developing irAEs, suggesting that careful follow-up is warranted., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Study Objectives: Poor adherence to continuous positive airway pressure (CPAP) has been a critical issue in treating obstructive sleep apnea. Because long-term CPAP adherence may be established shortly after treatment begins, early intervention is essential. This study aimed to identify the potential factors affecting CPAP therapy adherence during diagnostic polysomnography and auto CPAP titration polysomnography., Methods: This retrospective observational study included 463 patients with obstructive sleep apnea who underwent consecutive diagnostic polysomnography and titration polysomnography. We recorded their demographic, anthropometric, and lifestyle factors and obtained self-reported comments regarding their sleep status following both polysomnography evaluations. CPAP adherence was evaluated following 3 months of treatment., Results: A total of 312 patients (67.4%) fulfilled the criteria for good adherence. Each patient's CPAP adherence was categorized as "poor" (< 4 hours/night or <70% of nights), "good" (≥ 4 hours/night and ≥ 70% of nights), or "excellent" (≥ 6 hours/night and ≥ 80% of nights). There were no significant differences in arterial oxyhemoglobin saturation measured by pulse oximetry and apnea-hypopnea index during diagnostic polysomnography among 3 groups. The polysomnographic evaluations indicated that patients with better adherence displayed more significant improvements in sleep parameters, including apnea-hypopnea index, sleep efficacy, sleep latency, and sleep architecture, which were correlated with an improvement in self-reported sleep quality., Conclusions: Polysomnographic evaluations enabled CPAP adherence prediction and a comparison of self-reported sleep quality with and without CPAP; CPAP adherence led to improvements in polysomnographic parameters. Our findings suggest that titration polysomnography and self-reported sleep improvement with CPAP could be used for adherence prediction in clinical practice., Citation: Shirahata T, Uchida Y, Uchida T, et al. Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea. J Clin Sleep Med . 2023;19(8):1465-1473., (© 2023 American Academy of Sleep Medicine.)

Background: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy., Methods: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group)., Results: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001)., Conclusions: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The influence of sugammadex exposure during pregnancy on progesterone withdrawal and miscarriage is unknown. We aimed to compare the fetal outcomes in pregnant patients who had undergone non-obstetric surgery with and without sugammadex., Methods: We retrospectively reviewed the medical charts of pregnant women who underwent non-obstetric surgery at three tertiary perinatal care centers in Japan from January 2013 to December 2020. The women were divided into those who received general anesthesia with sugammadex (GA with SGX) and those who received general anesthesia without sugammadex (GA without SGX). We compared miscarriages and preterm births within four weeks after surgery., Results: Among the 124 women, 73 and 51 were included in the GA with SGX and GA without SGX groups, respectively. The two groups showed no differences in the rate of miscarriages or preterm births (3.0 % vs 4.3 %; odds ratio 1.42, 95 % confidence interval 0.19 to 10.47; P = 1.00). The SGX and no SGX groups were missing outcomes for 8.2 % and 7.8 % of cases, respectively., Conclusions: Having GA with SGX or GA without SGX did not result in different rates of miscarriage or preterm birth within four weeks after the procedure. These findings do not exclude a potential association between sugammadex exposure during pregnancy and adverse pregnancy outcomes. Missing data may have obscured possible adverse outcomes from sugammadex exposure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The clinical characteristics and risk factors for cancer recurrence have not been well evaluated regarding early recurrence in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) who receive concurrent chemoradiotherapy (CRT). The aim of this study was to determine the clinical characteristics and risk factors of patients with stage III unresectable LA-NSCLC treated with CRT who developed early recurrence., Methods: We retrospectively reviewed the clinical records of 46 patients diagnosed with stage III unresectable LA-NSCLC treated with CRT at our center between July 2012 and July 2021. A tumor proportion score (TPS) < 50% was defined as "low expression" and a TPS > 50% was defined as "high expression.", Results: A total of 17 (37.0%) patients had a confirmed recurrence within 1 year of treatment. More patients had a lower body mass index in the early recurrence group than in the later recurrence group (p = 0.038). A higher number of patients in the late recurrence group underwent surgery after CRT (p = 0.036). Patients with a higher TPS were more likely to experience late recurrence than early recurrence (p = 0.001), whereas more patients with stage N3 disease were in the early recurrence group (p = 0.011). Multivariate analysis identified lower TPS expression as an independent risk factor for early recurrence after CRT. Overall survival was prolonged in the late recurrence group (p < 0.001)., Conclusions: A lower TPS may be a predictor of early recurrence after CRT in patients with LA-NSCLC. These patients should be closely monitored for post-treatment recurrence., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Oxidative stress is known to activate tumor suppressor p53, which inhibits cell cycle progression and induces apoptosis. Levels of p53 in lung tissues from patients with chronic obstructive pulmonary disease (COPD) are increased compared with levels in nonsmokers or smokers without emphysema. A polymorphism in p53 codon 72 (rs1042522) is associated with emphysematous changes in patients with COPD. However, whether oxidative stress in the serum is associated with the p53 polymorphism and disease severity in COPD patients is unclear., Patients and Methods: A total of 251 patients with a history of smoking more than 10 pack-years were enrolled in this study, and serum levels of derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and d-ROMs/BAP ratio (oxidative stress index; OSI) were measured. The percent low-attenuation area (LAA%) and cross-sectional area of the erector spinae muscles (ESM CSA ) at the Th 12 level were calculated from chest high-resolution computed tomography images. p53 codon 72 C/G genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis., Results: In patients carrying the p53 GG genotype, LAA% was significantly higher than in those carrying the CC genotype. d-ROM levels and OSI were associated with COPD severity and correlated with airflow limitation and markers of muscle atrophy (ESM CSA and creatinine/cystatin C ratio). Associations between markers of oxidative stress and COPD severity were observed primarily in patients carrying the p53 codon 72 GG genotype., Conclusion: Susceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism., Competing Interests: The authors report no conflicts of interest in this work. The authors confirm that the data supporting the findings of this study are available within the article., (© 2022 Yamamura et al.)

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18 F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18 F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SUL max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SUL max , 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18 F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade., (© 2022. The Author(s).)

Background: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs., Methods: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021., Results: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059)., Conclusions: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Muscle atrophy is a major clinical feature of chronic obstructive pulmonary disease (COPD) and is considered a predictor of mortality in COPD patients. Recently, the cross-sectional area (CSA) of the erector spinae muscles measured by chest computed tomography (CT) scans (ESM CSA ) has been reported as a clinical parameter reflecting disease severity and future prognosis in patients with COPD. In addition, the serum creatinine (Cr)/cystatin C (CysC) ratio has been considered a quantitative marker of residual muscle mass, because serum Cr levels are affected by muscle mass, and correction by CysC counteracts the effect of renal function on serum Cr levels. The purpose of this study was to assess whether the serum Cr level corrected by serum CysC can be used as a predictive marker of pulmonary function and disease severity in patients with COPD., Patients and Methods: A total of 99 patients without COPD and 201 patients with COPD, with a smoking history of more than 10 pack-years were enrolled in this study, and serum Cr and CysC levels were measured. On chest high-resolution CT images, %low attenuation area (LAA%) (≤960 Hounsfield units (HU)) and ESM CSA at the Th 12 level were identified., Results: There was a significant correlation between the ESM CSA and the Cr/CysC ratio. The Cr/CysC ratio was significantly associated with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) values, especially in former smokers., Conclusion: The serum Cr/CysC ratio could be a convenient substitute for the measurement of muscle atrophy and pulmonary function testing in patients with COPD., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Nishiki et al.)

Yellow nail syndrome (YNS) is a rare disease comprising the clinical triad of yellow nail discoloration, pleural effusion, and lower limb lymphedema. We encountered a difficult-to-treat case of YNS in which the diagnosis was finally made based on intranodal lymphangiography. An 84-year-old man was admitted to our hospital with pleural effusion and yellow-green discoloration of the nails, accompanied by onychomycosis and limb lymphedema. Intranodal lymphangiography revealed a slow contrast flow and narrowing of the thoracic duct, suggesting lymphatic duct dysplasia and leading to the diagnosis of YNS.

Background: The risk of cancer treatment-related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified., Methods: We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021., Results: Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment-related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non-AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment-related AEs., Conclusions: Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment-related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear., Methods: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs., Results: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months ( p < 0.037) and 35.0 and 41.0 months ( p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs., Conclusions: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit.

Background: The effect of second-line treatment on overall survival (OS) may be affected by subsequent treatment in patients with non-small cell lung cancer (NSCLC); however, in such patients, the correlation between post-progression survival (PPS) and OS is unclear. Our study assessed the correlation of progression-free survival (PFS) and PPS with OS, using individual patient data, in advanced NSCLC patients who were treated with second-line nivolumab monotherapy, METHODS: Between January 2016 and March 2019, we evaluated 92 NSCLC patients who received second-line nivolumab treatment after first-line platinum-based combination chemotherapy. Using individual patient data, the correlations of PFS and PPS with OS were examined., Results: Linear regression and Spearman rank correlation analysis demonstrated that PPS was strongly correlated with OS (r = 0.85, p < 0.05, R 2 = 0.75), while PFS was moderately correlated with OS (r = 0.65, p < 0.05, R 2 = 0.42). Performance status at the beginning of second-line treatment, immune checkpoint inhibitor rechallenge, and the number of treatment regimens used post-progression, after the second-line treatment significantly correlated with PPS (p < 0.05). In advanced NSCLC patients who underwent second-line treatment with nivolumab, in comparison to PFS, there was a stronger correlation between PPS and OS., Conclusions: Our findings suggest that subsequent treatment for disease progression after a second-line nivolumab treatment had a significant impact on OS., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Immune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce., Methods: This study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed., Results: One hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39-84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group ( p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups., Conclusion: The administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group., Competing Interests: AM, KyK, OY, and HK received research grants and received honorarium as speakers from the Ono Pharmaceutical Company, Bristol-Myers Company, and Chugai Pharmaceutical Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mouri, Kaira, Yamaguchi, Hashimoto, Miura, Shiono, Shinomiya, Akagami, Imai, Kobayashi and Kagamu.)

Background: There is currently insufficient information available on effective therapies that can be administered to patients with non-small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, sequential treatment via programmed death-1 (PD-1) blockade followed by EGFR-TKI rechallenge is suggested to improve the therapeutic efficacy in such patients., Methods: A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR-TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR-TKI rechallenge immediately after the failure of PD-1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD-1 inhibitor therapy before EGFR-TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti-PD-1 therapy and at EGFR-TKI rechallenge., Results: The objective response rates of EGFR-TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression-free survival (PFS) and overall survival (OS) after EGFR-TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR-TKIs was observed in patients with partial response (PR) and without PR after EGFR-TKI rechallenge. In particular, the sequential treatment of PD-1 blockade therapy followed by EGFR-TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR-TKI rechallenge consecutively for the third time yielded a PR without increased toxicities., Conclusions: EGFR-TKI rechallenge immediately after PD-1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR-TKIs., (© 2021The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings., Methods: In this single-institution retrospective study conducted from May 2017 to October 2019, pembrolizumab was administered to 72 Japanese patients with treatment-naïve advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥50%. Patients with ILD were assigned to the ILD group, and those without to the non-ILD group. Between-group comparisons were then performed., Results: Of the 72 patients, 61 (84.7%) were male. The median age was 70 years. A total of 64 patients (88.9%) had a smoking history, median PD-L1 TPS status was 77.5%, and 10 of the 72 patients (13.9%) had ILD on pretreatment computed tomography. The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 75.0%. The ORR was 70.0% and DCR was 90.0% in the ILD group, while the ORR was 41.9% and DCR was 72.6% in the non-ILD group. The median overall survival was 568 days; the value in the non-ILD group was 521 days, while in the ILD group was not reached. There was no significant difference between the two groups (log-lank, P = 0.73)., Conclusions: Pembrolizumab was administered to patients with pre-existing ILD with no difference in prognosis compared to patients without ILD. In patients with ILD, physicians should consider the expected long-term prognosis and risk of adverse events., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: In Japan, approximately half of all lung cancer patients are aged > 75 years, and the proportion of older patients is increasing. In older patients, it is necessary to consider comorbidities and concomitant drug use to ensure optimal cancer treatment; however, geriatric assessment (GA) is not widely performed. We plan to conduct a study (ENSURE-GA) of GA in older lung cancer patients to determine whether GA with intervention improves patient satisfaction with their treatment., Methods: The study will be a phase III comparative clinical trial with a cluster-randomized design, and it will be conducted at 81 sites distributed throughout Japan. Approximately 1000 lung cancer patients aged ≥ 75 years will be enrolled in the study. All participants will undergo a standardized GA before starting treatment (using an iPad). At the intervention sites, the GA results and intervention method recommended on the basis of the GA results will be returned as an instant report to guide the physician's choice of intervention. At the control sites, the physician will decide on interventions based on standard practice. All participants will complete a patient satisfaction survey before treatment initiation (after the GA) and 3 months later., Discussion: The purpose of the ENSURE-GA study is to evaluate whether GA with interventions improves patient satisfaction with treatment outcomes. The study may lead to the increased use of GA and improved treatment of cancer in older adults. The results will also be used to prepare guidelines for treating older cancer patients and will provide a foundation for the development of a standardized geriatric oncology system., Trial Registration: The study has been registered in the University Hospital Medical Information Network database (no. UMIN000037590). The registration date is August 4, 2019, and the protocol version is 2.0. ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000042853 .).

Background: The feasibility and safety of laparoscopic extensive resection (ER) for complicated appendicitis (CA) has not been clarified. We assessed the feasibility of laparoscopic ER versus open ER for CA., Methods: We retrospectively enrolled consecutive 983 patients who underwent emergency surgery for appendicitis, including 91 patients who underwent ER for CA, between April 2007 and October 2019., Results: Thirty-three patients underwent laparoscopic ER, and 58 patients underwent open ER. There were no significant differences in the reasons for performing ER between laparoscopic ER and open ER. The rates of suspicious for malignant tumor did not differ between laparoscopic and open ER [15.2% (5/33) vs. 17.2% (10/58)]. Blood loss was less in laparoscopic ER than in open ER (P=0.028). Superficial surgical site infection was less frequent in laparoscopic ER than in open ER (P=0.047). In addition, laparoscopic ER tended to be associated with a shorter hospital stay, lower rate of postoperative ileus, and higher rate of intra-abdominal abscess., Conclusion: Laparoscopic ER is feasible, and it is associated with less intraoperative blood loss and a lower frequency of postoperative superficial surgical site infection than open ER., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Lung cancer patients presenting with osteoblastic bone metastases at the first visit is rare. We investigated the clinical characteristics and gene mutation rate of non-small cell lung cancer patients with osteoblastic bone metastases at the time of the initial diagnosis., Materials and Methods: We retrospectively screened newly diagnosed non-small cell lung cancer patients with osteoblastic bone metastases who presented from June 2015 to March 2021, and analyzed their clinical characteristics and status of EGFR gene mutations, EML4-ALK translocation and ROS1 rearrangements. For comparison, we collected data from patients with non-small cell lung cancer who had osteolytic bone metastases at their first visit between June 2015 and March 2021., Results: Fifty patients had bone metastases at the initial diagnosis. Among them, eight patients (8/50 = 16%) had osteoblastic bone metastases, and the lung tumors in all of them were histopathologically adenocarcinomas. Among the eight cases, two were EGFR mutation-positive, none were EML4-ALK translocation-positive, two were ROS1 rearrangement-positive, and the remaining four cases were negative for all three gene mutations/rearrangements. Compared with the osteolytic bone metastasis group, the percentage of non-smokers was higher (p = 0.020) and the ROS1 rearrangement positivity rate was higher (p = 0.05) in the osteoblastic bone metastasis group., Conclusion: Our results indicate that osteoblastic bone metastases in NSCLC are suggestive of adenocarcinoma, and that a high proportion of these patients might be positive for ROS1 rearrangements, and hence, indicated for more aggressive diagnostic biopsies., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Self-expandable metallic stent (SEMS) placement is an urgent procedure for patients with malignant central airway stenoses (CASs) and central airway fistulas (CAFs). The aim of this study was to determine the outcome and survival after SEMS placement in patients with malignant CASs and CAFs., Methods: SEMSs were inserted into 20 patients with malignant CASs and four with malignant CAFs. Hospital records, the modified Medical Research Council dyspnea scale (mMRC) grade, performance status (PS), symptoms, procedure-related complications and survival after placement were retrospectively reviewed., Results: Spiral Z stents were inserted in nine patients, covered Ultraflex stents in 14, and a bare Ultraflex in one patient. After SEMS placement, 20 patients (83.3%) showed improvement in mMRC grade, 19 (79.2%) showed improvement in PS, and 21 (87.5%) showed improvement in symptoms. There were three patients whose stents migrated out of place, but there were no patients with obstructive granulation, infection, or mucous plugs. Median survival days after stent insertion was 98 days for CAS and 103 days for CAF, and mean survival days was 383 ± 707 days for CAS and 93 ± 33 days for CAF. Two patients with CAS by malignant lymphoma and thymic cancer survived more than six years because they were also treated with efficient therapies. The five-year survival rate after stent insertion was 7.7%., Conclusions: SEMS placement for CAS and CAF is associated with improvement in mMRC grade, PS and symptoms in 87.5% of patients. Patients with a malignant CAS are usually terminal, but the possibility of increasing survival rate will become a reality with new efficient therapies., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Reasonable clinical outcomes and improved survival of patients following SEMS placement for thoracic malignancy with central airway stenosis and fistula., What This Study Adds: The possibility of increasing survival rate will become a reality with new efficient therapies., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare tumor with an aggressive clinical course. However, there is limited knowledge of its treatment strategy. This retrospective study aimed to assess the efficacy and safety of anti-programed death-1 (PD-1) blockade monotherapy in previously treated advanced LCNEC., Methods: Eleven patients with previously treated advanced LCNEC who received immune checkpoint inhibitor monotherapy between January 2015 and November 2020 were retrospectively analyzed for efficacy and safety., Results: Of a total of 11 patients (median [range] age, 66 [37-79] years; 8 men [73%] and 3 women [27%]), 8 patients had performance status (PS) 0-1 [73%] and 3 patients had PS 2 [27%]; 9 patients received 1 prior chemotherapy [82%] and 2 patients received 2 prior chemotherapies [18%]. The median follow-up duration was 4.6 months. Although PD-1 blockade was administered at median cycles of 3 (range, 1-12), overall response rate, median progression-free survival, and median overall survival were 9.1%, 2.7 months, and 4.6 months, respectively. Any adverse events were observed in 9 patients (82%), including 1 patient with grade 3 pneumonitis as a serious adverse event., Conclusion: Anti-PD-1 blockade monotherapy as a subsequent line for previously treated advanced LCNEC exhibited usefulness and tolerability and was identified as a valid treatment option., (© 2021 S. Karger AG, Basel.)

Rationale: Cardiotoxicity related to osimertinib, including cardiac failure, QT prolongation, and atrial fibrillation, has been reported as an extremely rare incidence in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of osimertinib-induced cardiomyopathy., Patient Concerns: A 76-year old woman was treated with afatinib (40 mg/day) as the 1st line treatment due to recurrence after surgical resection for pulmonary adenocarcinoma. However, she experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy., Diagnosis: Four months after osimertinib initiation, she complained of fever and progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating osimertinib-induced cardiomyopathy., Interventions and Outcomes: She was treated with furosemide, carvedilol, and enalapril, and her cardiac function, her symptoms, and condition improved 3 weeks after the withdrawal of osimertinib., Lessons: Physicians should be alert of the cardiomyopathy-causing potential of osimertinib in advanced NSCLC patients.

Background: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non-small cell lung cancer (NSCLC). There is a real-world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice., Methods: From July 2018 to August 2019, 41 patients with locally advanced NSCLC, who underwent chemoradiotherapy followed by durvalumab, were retrospectively analyzed in the study using our medical records., Results: The median age of patients was 72 years (range: 51-80 years). A total of 33 patients were male and eight were female, and 40 patients (98%) received a total radiation dose of 60 Gy as concomitant chemoradiotherapy. The median V20 for the entire cohort was 18.9% (range: 3.5-29.9). Any adverse events during chemoradiotherapy and durvalumab were observed in 32 patients (78.0%), while three patients (7.3%) experienced grade 3 toxicities. In total, 25 (61.0%) patients experienced pneumonitis, four (9.8%) thyroid dysfunction, three (7.3%) myopathy, two (4.9%) rash or eruption, one (2.4%) bowel disease and one (2.4%) malaise. Grade 3 pneumonitis, thyroid dysfunction and myopathy were observed in one (2.4%), one (2.4%) and one (2.4%), respectively. A total of 22 (53.7%) patients were unable to continue durvalumab due to pneumonitis. However, durvalumab was finally readministered to six patients., Conclusions: The adherence to lung dose constraints such as V20 as well as close treatment monitoring are a prerequisite for the management of pneumonitis during maintenance therapy with durvalumab., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Limited information is available on the occurrence of synchronous malignancy in patients with advanced thymic cancer (TC) who have achieved long-term survival due to sequential chemotherapy. Here, we present two cases of hematological malignancies in long-term survivors with advanced TC., Case Reports: A 56-year-old man underwent surgical resection following the diagnosis of TC with a histological indication of squamous cell carcinoma. He received sequential chemotherapy, including carboplatin plus paclitaxel, amrubicin, and S-1, due to multiple pulmonary metastases. After >4 years of first-line chemotherapy, he developed consistent myelosuppression and a definite diagnosis of acute promyelocytic leukemia was made following bone marrow analysis. A 49-year-old man with advanced TC received carboplatin plus paclitaxel with amrubicin as second-line therapy due to recurrence. Amrubicin was administered for 54 cycles but T-cell lymphoblastic lymphoma without recurrence of TC was confirmed following transbronchial nodal biopsy due to marked lymphadenopathy., Conclusion: Physicians should be alert to the occurrence of hematological malignancy in patients with thymic cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment., Methods: In this single-institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the EGFR mutation., Results: Of the 47 patients, 20 (42.6%) were men and 27 (57.4%) were women. The median age was 71 years (range 37-83 years). A total of 19 patients (40.4%) had a smoking history. Furthermore, seven patients (14.9%) received osimertinib immediately after nivolumab therapy, while 40 patients (85.1%) were treated with osimertinib after treatment with drugs other than nivolumab. The frequency of grade 3 or 4 hepatotoxicity was significantly higher in patients with nivolumab prior to osimertinib (4/7; 57.1%) than in those treated with drugs other than nivolumab prior to osimertinib (2/40; 5.0%) (P = 0.0026). Liver biopsies were performed in two patients who received osimertinib immediately after nivolumab. In both patients, CD-8-positive T cell infiltration was predominantly observed in the liver tissues., Conclusions: The use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboring EGFR mutation acquired T790M resistance., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Minnamide A is a lipopeptide with a unique repeating structure consisting of hydroxy and proposed β-branched methyl groups. The absolute configuration of minnamide A was determined by a combination of chemical degradation, chiral HPLC analyses, and synthetic methods. Minnamide A showed growth-inhibitory activity toward HeLa cells with an IC 50 value of 0.17 μM and rapidly induced cell death at a concentration of 2 μM. Minnamide A induced the copper-mediated accumulation of reactive oxygen species.

Background: The use of microscopic computed tomography to assess the key functional parameters of systolic emptying or diastolic filling in small animals has not been previously reported. The aim of the study was to test whether microscopic computed tomography can assess the dynamics of both left ventricle and right ventricle (RV) diastolic filling and systolic emptying in an experimental model of pulmonary arterial hypertension Methods and Results: The Wistar-Kyoto rats were injected subcutaneously with the VEGF (vascular endothelial growth factor)-receptor inhibitor SU5416 (20 mg/kg body weight) and were then exposed to chronic hypoxia (10% oxygen) for 21 days (SU5416-hypoxia) followed by normoxia for an additional 2 weeks. Thereafter, multiphase cine cardiac images were acquired using a microscopic computed tomography scanner in conjunction with a blood-pool iodinated contrast agent. Examination of the 3-dimensional images of SU5416-hypoxia rats confirmed the presence of severe pulmonary arterial hypertension. Functional parameters that describe the dynamics of ventricular systolic ejection and diastolic filling were calculated. RV peak ejection rate was significantly decreased ( P<0.03) in SU5416-hypoxia rats compared with controls. RV peak filling rate had a significant decrease compared with controls ( P<0.03), particularly in the early phase of diastole ( P<0.03). This was accompanied by increased time to peak filling rate ( P<0.03) and total filling time ( P<0.06). Spearman analysis between microscopic computed tomography RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation., Conclusions: We developed a method that allows rapid and accurate assessment of cardiac functional indices and that paves the way for more extensive preclinical cardiovascular research.

In 2014, the γ-pyrone-containing polyketide, yoshinone A, was isolated from the marine cyanobacterium Leptolyngbya sp. and its structure was determined. Yoshinone A inhibited differentiation of 3T3-L1 cells into adipocytes, with an EC 50 value of 420 nM without any cytotoxicity, and therefore is expected to be a lead compound for obesity drugs. To establish its absolute configuration, and to provide sufficient amounts for further research, the total synthesis of yoshinone A was achieved through synthesis of its two possible diastereomers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (TPR), and airway pressure (AWP) to angiotensin II, endothelin-1, vasopressin, phenylephrine, and thromboxane A2 analog U46619 in anesthetized BALB/c mice. Pulmonary arterial pressure, left atrial pressure (LAP), and aortic blood flow were measured. TPR increased dose-dependently in response to consecutive administration of all vasoconstrictors except vasopressin which reduced TPR at the highest dose of 100 nmol/kg. At high doses of vasoconstrictors, pulmonary arterial pressure and AWP increased due to increased LAP, as demonstrated by the separate LAP elevation experiments. When LAP transiently increased at high doses, PVR did not increase but decreased. Nonetheless, enodothelin-1, angiotensin II, and U46619 increased PVR. Vasopressin at 100 nmol/kg increased AWP without LAP elevation. In conclusion, the high doses of the vasoconstrictors studied here exert indirectly a transient pulmonary vasodilatory and AWP increasing actions due to pulmonary congestion evoked by strong systemic vasoconstriction. Nevertheless, enodothelin-1, angiotensin II, and U46619 cause pulmonary vasoconstriction, and vasopressin constricts airway in anesthetized BALB/c mice.

The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.e., errors of the estimated areas in the closer distances accumulate to those in the further distances. Here we present a new technique of acoustic reflection from measuring transmitted acoustic waves in the airway with three microphones and without employing a wave tube. Using miniaturized microphones mounted on a catheter, we estimated reflection coefficients among the microphones and separated incidental and reflected waves. A model study showed that the estimated cross-sectional area vs. distance function was coincident with the conventional two-microphone method, and it did not change with altered cross-sectional areas at the microphone position, although the estimated cross-sectional areas are relative values to that at the microphone position. The pharyngeal cross-sectional areas including retropalatal and retroglossal regions and the closing site during sleep was visualized in patients with obstructive sleep apnea. The method can be applicable to larger or smaller bronchi to evaluate the airspace and function in these localized airways.

Systemic anaphylaxis accompanies pulmonary vasoconstriction and bronchoconstriction, which may contribute to increased right heart afterload, and finally anaphylactic hypotension. However, the pulmonary response to anaphylaxis is not known in mice. We determined the pulmonary vascular and bronchial response to systemic anaphylaxis in anesthetized BALB/c mice. We also clarified the roles of β-adrenoceptors, nitric oxide, and cyclooxygenase metabolites in these responses. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure, systolic pulmonary arterial pressure, central venous pressure, airway pressure, and aortic blood flow were continuously measured. In sensitized control mice, mean arterial pressure, and aortic blood flow substantially decreased soon after the antigen injection, while systolic pulmonary arterial pressure and airway pressure did not increase. In contrast, in mice pretreated with either the β(2)-adrenoceptor antagonist ICI 118,551 (0.2 mg/kg; n = 6), or L-NAME (50 mg/kg; n = 6), but not with the β(1)-adrenoceptor antagonist atenolol (2 mg/kg; n = 6) or indomethacin (5 mg/kg; n = 6), systolic pulmonary arterial pressure increased by 7 mmHg at 1.5 min after antigen. In L-NAME pretreated mice, pulmonary hypertension was sustained over 30 min of the experimental period. Airway pressure did not significantly change after antigen in any mice studied. In conclusion, pulmonary response to systemic anaphylaxis does not increase the right heart afterload and, therefore, may not contribute to the initial decrease in venous return and anaphylactic hypotension in anesthetized mice. β(2)-adrenoceptor activation and nitric oxide, but not β(1)-adrenoceptor activation or cyclooxygenase metabolites, attenuate the antigen-induced pulmonary vasoconstriction.

In collaboration between the in-hospital nutrition support team and infection control team, we attempted to standardize the management of infusion therapy. We report on a simple and effective at-home infusion therapy, after total parenteral nutrition(TPN)therapy, by using a Broviac catheter in a discharged patient with a severe skin condition. The patient was a man in his 50s who had amyloidosis. Because of dysphagia and complications of the digestive organs, TPN was chosen as the method for nutritional management. At the beginning the patient repeated infection and a trouble of the skin, but the insertion site was managed by the existing standardized manual. However, switching to a Broviac catheter improved the existing disease. Dermatopathy was improved and there was no catheter-related bloodstream infection under the new management method. Furthermore, the patient is now able to feed orally. Patients should be evaluated individually, and for the case that is hard to care with a manual, it is necessary to choose the best possible method.

To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.