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In hospitalized coronavirus disease 2019 (COVID-19) patients, anticoagulation therapy is administered to prevent thrombosis. However, anticoagulation sometimes causes bleeding complications. We herein report two Japanese cases of severe COVID-19 in which spontaneous muscle hematomas (SMH) developed under therapeutic anticoagulation with unfractionated heparin. Although the activated partial prothrombin time was within the optimal range, contrast-enhanced computed tomography (CECT) revealed SMH in the bilateral iliopsoas muscles in both cases, which required emergent transcatheter embolization. Close monitoring of the coagulation system and the early diagnosis of bleeding complications through CECT are needed in severe COVID-19 patients treated with anticoagulants.

Background This study aimed to examine risk factors associated with critical coronavirus disease 19 (COVID-19) and to establish a risk predictive model for Japanese patients. Methods We retrospectively assessed adult Japanese patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center, Tokyo, Japan between February 1, 2020 and March 10, 2021. The patients were divided into critical and non-critical groups based on their condition during the clinical courses. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between clinical characteristics and critical illness. Based on the results, we established a predictive model for the development of critical COVID-19. Results In total, 300 patients were enrolled in this study. Among them, 86 were included in the critical group. Analyses revealed that age ≥65 y, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL were independently associated with the development of critical COVID-19. Next, a predictive model for the development of critical COVID-19 was created, and this included the following variables: age ≥65 y, male sex, diabetes, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL. The area under the receiver operating characteristic curve of the model was 0.86 (95% confidence interval, 0.81–0.90). Using a cutoff score of 12, the positive and negative predictive values of 74.0% and 80.4% were obtained, respectively. Conclusions Upon diagnosis, the predictive model can be used to identify adult Japanese patients with COVID-19 who will require intensive treatment.

Background Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib—a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. Methods Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. Results In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively. Conclusions Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.

Skeletal muscle atrophy often complicates idiopathic pulmonary fibrosis (IPF). IPF patients frequently experience acute exacerbation (AE), but the association between skeletal muscle atrophy and mortality remains unknown in AE-IPF patients. Herein, cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) of AE-IPF patients were analysed via computed tomography. Primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan–Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. Among the 212 patients, 94 (44%) died during the observation period. The low ESMCSA group (2) had a significantly worse prognosis than the high group (≥ 25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00–2.33], p = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98–2.60]; model 2, 1.55 [0.95–2.56] and model 3, 1.67 [1.00–2.78]). A similar trend was observed between low PMCSA and poor prognosis (HR [95% CI]: 1.39 [0.88–2.20]). In conclusion, low ESMCSA is associated with high 90-day mortality in AE-IPF patients.

The prolonged pandemic of coronavirus disease 2019 (COVID-19) has resulted in mental burden among healthcare workers (HCWs). This study aimed to conduct a repeated study to assess changes in psychological concerns among Japanese HCWs.This study is the second survey involving HCWs at the Japanese Red Cross Medical Center conducted between November 20, 2020 and December 4, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale, Center for Epidemiologic Studies Depression Scale, and 10-item Connor-Davidson Resilience Scale, respectively.The survey included 594 HCWs, comprising 95 physicians, 261 nurses, 150 other co-medical staff, and 88 office workers. Among them, 46 (7.7%) and 152 (25.6%) developed moderate-to-severe symptoms of anxiety and depression, respectively. Compared with those in the initial survey conducted 6 months earlier, the resilience score did not change, whereas the anxiety and depression scores improved significantly (P0.001, P = 0.033, respectively). However, the frequency of HCWs developing moderate-to-severe symptoms of anxiety or depression did not significantly improve. Multivariable logistic regression analysis showed that having higher anxiety symptoms was a risk factor for depression symptoms, while older HCWs and those with higher resilience were less likely to develop depression symptoms.Many HCWs still suffer from psychological concerns during the COVID-19 pandemic.

Background The association of treatment-induced tumor shrinkage with symptom palliation for patients with lung cancer remains unknown. We investigated this correlation using the Edmonton Symptom Assessment System–Revised. Methods Using the in-hospital cancer registry, we identified patients receiving chemotherapy and/or immunotherapy for newly diagnosed advanced or metastatic lung cancer. Tumor response and post-treatment Edmonton Symptom Assessment System–Revised were obtained after 2–3 treatment cycles. Patients were divided into groups with or without >30% unidirectional tumor shrinkage (objective response [OR] or non-OR [N-OR] groups, respectively). They were further classified as good-objective response (>50% unidirectional tumor shrinkage), moderate-objective response (30–50% shrinkage), progressive disease (>20% tumor growth or new lesion) or stable disease (SD; N-objective response and non-progressive disease). The primary endpoint was change in the total Edmonton Symptom Assessment System–Revised score from baseline. The Mann–Whitney U test was used for analysis. Results In total, 113 patients were enrolled. The total Edmonton Symptom Assessment System–Revised score was significantly more improved in the OR group versus the N-OR group (median: 5 vs. 2, respectively; P = 0.013). This association was more prominent in patients with small-cell lung cancer and large-cell neuroendocrine tumor than those with other histology. Sensitivity analyses showed that the total Edmonton Symptom Assessment System–Revised score was more improved in the OR group versus the SD group (median: 5 vs. 3, respectively; P = 0.029) and in the ‘good-OR’ group versus the ‘moderate-OR and SD’ group (median: 7.5 vs. 2, respectively; P = 0.003), suggesting that greater tumor shrinkage led to more symptom amelioration. Conclusions Tumor shrinkage was associated with Edmonton Symptom Assessment System–Revised score improvement in patients with lung cancer receiving systemic therapy.

Objective Coronavirus disease 2019 (COVID-19) is spreading around the world. The aim of this study was to assess the degree of anxiety, depression, resilience, and other psychiatric symptoms among healthcare workers in Japan during the COVID-19 pandemic. Methods This survey involved medical healthcare workers at the Japanese Red Cross Medical Center (Tokyo, Japan) between April 22 and May 15, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale (GAD-7), Center for Epidemiologic Studies Depression Scale (CES-D), and 10-item Connor-Davidson Resilience Scale. Furthermore, we added original questionnaires comprising three factors: (i) anxiety and fear of infection and death; (ii) isolation and unreasonable treatment; and (iii) motivation and escape behavior at work. Results In total, 848 healthcare workers participated in this survey: 104 doctors, 461 nurses, 184 other co-medical staff, and 99 office workers. Among all participants, 85 (10.0%) developed moderate-to-severe anxiety disorder, and 237 (27.9%) developed depression. Problems with anxiety and fear of infection and death, isolation and unreasonable treatment, and motivation and escape from work were higher in the depression group than in the non-depression group (total CES-D score ≥ 16 points). Being a nurse and high total GAD-7 scores were risk factors of depression. Older workers and those with higher resilience were less likely to develop depression than others. Conclusion During the COVID-19 epidemic, many healthcare workers suffered from psychiatric symptoms. Psychological support and interventions for protecting the mental health of them are needed.

Objective Patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT) are at a risk of CO2 retention because of excessive oxygen administration. The CapnoEye™ is a novel portable capnometer that can measure end-tidal CO2 (EtCO2) noninvasively. This retrospective study evaluated the usefulness of this device. Methods EtCO2 was measured using the CapnoEye™. The EtCO2 and partial pressure of venous carbon dioxide (PvCO2) were analyzed, and other clinical data were assessed. Patients Sixty-one consecutive patients with chronic respiratory failure receiving LTOT in the outpatient department at the Japanese Red Cross Medical Center between July 2017 and March 2018 were retrospectively reviewed. Results There was a significant correlation between EtCO2 and PvCO2 (r=0.63) in the total study population as well as in the COPD group (r=0.65) and ILD group (r=0.67). The PvCO2 and EtCO2 gradient was correlated with only the body mass index in a multivariate analysis (p=0.0235). The EtCO2 levels on the day of admission were significantly higher than those in the same patients when they were in a stable condition (p=0.0049). There was a significant correlation between ΔEtCO2 and ΔPvCO2 (r=0.4). A receiver-operating characteristic curve analysis revealed the optimal cut-off EtCO2 value for identifying hypercapnia to be 34 mmHg (p=0.0005). Conclusion The evaluation of EtCO2 by the CapnoEye™ was useful for predicting PvCO2. The body mass index was identified as a possible predictor of the PvCO2 and EtCO2 gradient. An increase in EtCO2 may indicate deterioration of the respiratory status in patients with chronic respiratory failure receiving LTOT.

Immune checkpoint inhibitors have changed the landscape of classic cancer treatment. However, their use is associated with the emergence of new adverse events. An elderly man with rheumatoid arthritis was started on pembrolizumab for newly diagnosed advanced lung cancer. He subsequently developed hemophagocytic lymphohistiocytosis (HLH), which is potentially fatal but has not been properly established as an immune checkpoint inhibition-induced event. We herein report the case of a patient with pembrolizumab-induced HLH.

AIM The current study reports the type of salvage chemotherapy following osimertinib and its treatment efficacy in patients with non-small-cell lung carcinoma (NSCLC) who acquire resistance to osimertinib. PATIENTS AND METHODS In this retrospective cohort study, data from the medical charts of 40 patients with NSCLC treated with osimertinib were obtained, primarily focusing on 14 undergoing salvage chemotherapy including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) or cytotoxic agents immediately following osimertinib. The treatment efficacy of salvage chemotherapy was evaluated. RESULTS Five and nine patients received EGFR-TKI and cytotoxic agents following osimertinib, respectively. The overall response rate to EGFR-TKI treatment following osimertinib tended to be lower than that for cytotoxic agents (0% vs. 44.4%). The median progression-free-survival was significantly poorer in patients receiving EGFR-TKI treatment than in those receiving cytotoxic agents. CONCLUSION Cytotoxic agent administration should be considered more frequently than EGFR-TKIs for patients with NSCLC resistant to osimertinib.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.

BackgroundRadial endobronchial ultrasonography (R-EBUS) has been used in conjunction with transbronchial lung cryobiopsy (TBLC) to diagnose diffuse parenchymal lung disease (DPLD) and to decrease the risk of bleeding complications. The diagnostic utility of different R-EBUS signs, however, remains unknown.ObjectivesThis study aimed to determine whether different R-EBUS signs could be used to more accurately diagnose DPLD and whether bronchial bleeding could be prevented with use of R-EBUS during TBLC.MethodEighty-seven patients with DPLD were included in this multicentre prospective study, with 49 patients undergoing R-EBUS. R-EBUS signals were characterised as displaying either dense or blizzard signs. Pathological confidence of specimens obtained from TBLC was compared between patients with dense versus blizzard signs, and severity of bronchial bleeding was determined based on whether R-EBUS was performed or not.ResultsAll patients with dense signs on R-EBUS showed consolidation on high-resolution CT (HRCT) imaging. Pathological confidence of lung specimens was significantly higher in patients with dense signs versus those with blizzard signs (pConclusionsThe dense R-EBUS sign corresponded with consolidation on HRCT. High-quality lung specimens may be obtainable when the dense sign is observed on R-EBUS, and R-EBUS combined with TBLC may reduce risk of bronchial bleeding and shorten procedure times.

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Background The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear. Methods The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition. Results In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p

Introduction: The frequency of detection of peripheral pulmonary lesion (PPL) in suspected early lung cancer has been increasing, and whether preoperative pathological diagnosis (PPD) for small PPLs should always be established before their surgical resection can become a worrisome problem for physicians. The aim of the study was to clarify the impact of obtaining PPD on surgical and postoperative outcomes of lung resection for early stage lung cancer. Material and methods: This was a retrospective review of cases that underwent surgical resection for known or suspected primary lung cancer presenting pathological stage 0 or I, enrolled from June 2006 to May 2016. The patients divided into two groups according to PPD group (n = 57) and non-PPD group (n = 157) were compared. The procedure, node dissection, operation time, amount of bleeding, postoperative complications, postoperative length of stay, and postoperative recurrences were analyzed. Results: Among the 214 patients, no significant differences in operation time (248.5 ± 88.6 versus 257.6 ± 89.0, min, mean ± SD, p = 0.328), amount of bleeding (195.3 ± 176.5 vs. 188.1 ± 236.1, mL, p = 0.460), postoperative complication (5.2% vs. 4.5%, p = 0.728), postoperative length of stay (10.6 ± 6.3 vs. 10.4 ± 5.3, days, p = 0.827), or postoperative recurrences (21.0% vs. 17.2%, p = 0.550) were seen between PPD and non-PPD groups. Conclusions: Therefore, PPD had less impact on surgical and postoperative outcomes of pathological stage 0 or I lung cancer; direct surgical resection without non-surgical biopsy would be acceptable with careful selection of cases.

Severe bronchial asthma is a chronic disorder of the airways that may be accompanied by comorbid diseases. Invasive treatment, including surgery, in patients with severe asthma has limitations depending on the degree of control of the asthma. A 71-year-old woman was diagnosed with squamous cell carcinoma with high programmed death-ligand 1 (PD-L1) expression and cT3N0M1a. After 13 cycles of pembrolizumab every 3 weeks, chest computed tomography (CT) revealed a dramatic decrease in the lesion size in the left upper lobe, but the size of the lesion in the right lower lobe was significantly increased. The pathological findings of the right residual tumor by CT-guided transthoracic needle biopsy (CTNB) revealed squamous cell carcinoma with no PD-L1 expression, and right lower lobectomy was recommended. However, because the patient had frequent asthma attacks and cough, surgery was considered risky. Increased blood eosinophil count was observed, and benralizumab was administered for asthma control. The symptoms disappeared 2 days after benralizumab administration, and peak flow increased. Surgery was performed 5 days after benralizumab administration. There was a marked reduction in the eosinophil count of the surgical tissue compared with the preoperative CTNB tissue. No asthma attacks were observed during and after surgery, and the control of asthma and lung cancer was stable. Benralizumab is considered promising for the treatment of eosinophilic severe uncontrolled asthma. Keywords: Interleukin-5 receptor α monoclonal antibody, Immune checkpoint inhibitor, Lung cancer, Severe uncontrolled asthma, Video-assisted thoracic surgery

Background Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. Case presentation An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. Conclusions We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

BackgroundThe use of several promising drugs for coronavirus disease 2019 (COVID-19) has emerged. However, considering the pathophysiology of COVID-19, the effect of a single agent is limited. Hence, the current study aimed to compare the clinical outcomes between patients who received combination treatment with remdesivir, dexamethasone, and tocilizumab (RDT) and those who did not.MethodsPatients who received combination therapy with RDT at Japanese Red Cross Medical Center were included in the RDT group, and those who did not in the control group. The mortality rate and presence of severe adverse events were compared between the two groups.ResultsIn total, 46 patients (n = 29, control group and n = 17, RDT group) with severe COVID-19 were enrolled in this study. The 28-day mortality rate was significantly lower in the RDT group than in the control group, with 1 (6%) and 9 (31%) deaths recorded, respectively (P = 0.04). Further, both groups did not present with severe adverse events.ConclusionsInformation on the outcomes of combination therapy with RDT was considered useful for the treatment of severe COVID-19.

Background Most lung cancer patients present with lesions in both lung fields and lymphadenopathy. Thus, transbronchial lung cryobiopsy (TBLC) and endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are commonly performed for diagnosing lung cancer. However, the adequacy of these samples for next‐generation sequencing (NGS) analysis remains unclear. This study aimed to compare the adequacy between TBLC and EBUS‐TBNA samples for NGS analysis. Methods This retrospective cohort study included patients whose lung samples were collected via TBLC or EBUS‐TBNA and analyzed using NGS. Out of 46 genes, the number of genes in TBNA and TBLC samples that could not be assessed via NGS analysis was mainly evaluated. Results A total of 37 patients were included and classified into two groups (TBLC group, n = 18 and TBNA group, n = 19). The mean number of genes that could not be evaluated via NGS analysis was significantly lower in the TBLC group than in the TBNA group (0.9 vs. 10.3, P = 0.024). The median total area of tumor cells in TBLC samples was significantly greater than that in TBNA samples (6.3 [1.6–4.2] vs. 2.6 [0.2–17.3] mm2, P, The adequacy for next generation sequencing (NGS) in transbronchial lung cryobiopsy (TBLC) and endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) samples remains unclear. We found the mean number of genes which could not be assessed via NGS was significantly lower in TBLC samples than EBUS‐TBNA samples. TBLC could obtain adequate samples with a high concentration of uncrushed tumor cells for NGS.

Objective The medical costs associated with cancer treatment have increased rapidly in Japan; however, little data exist on actual costs, especially for end-of-life care. Therefore, this study aimed to examine the medical costs of lung cancer patients during the last 3 months before death and to compare the costs with those of initial anticancer treatment. Methods We retrospectively evaluated all patients who died from lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 August 2019. Patients were classified into three cohorts (2008–2011, 2012–2015 and 2016–2019) according to the year of death; the medical costs were evaluated for each cohort. Costs were then divided into outpatient and inpatient costs and calculated per month. Results Seventy-nine small cell lung cancer and 213 non-small cell lung cancer patients were included. For small cell lung cancer and non-small cell lung cancer patients, most end-of-life medical costs were inpatient costs across all cohorts. The median monthly medical costs for the last 3 months among both small cell lung cancer and non-small cell lung cancer patients did not differ significantly among the cohorts, but the mean monthly costs for non-small cell lung cancer tended to increase. The monthly medical costs for the last 3 months were significantly higher than those for the first year in SCLC (P = 0.013) and non-small cell lung cancer (P Conclusions The medical costs during the end-of-life period for lung cancer were high and surpassed those for initial treatment.

Objective In 2014, an autochthonous dengue fever outbreak occurred around the Yoyogi Park in Japan for the first time in 70 years. Despite no local cases reported since then, the risk of another outbreak remains high. This study reviews the autochthonous dengue fever cases of the outbreak, investigates its causes, and delineates preventive measures against autochthonous dengue epidemics. Methods We conducted a case series study of 15 patients who visited our institution during the 2014 outbreak. We collected and evaluated data on the surveillance of vector mosquitoes, weather, pest control, travelers’ origins and destinations, and imported dengue fever cases using reports made by public institutions. Results All patients recovered with supportive treatments and none met the diagnostic criteria for severe dengue infection. Twelve patients with positive real-time polymerase chain reactions were confirmed as having dengue virus-1 infections. We found no obvious associations between the number of mosquitoes and the weather, or between the number of imported dengue fever cases and that of travelers. Insect growth regulator (IGR) against vector mosquitoes has been used since 2014 for pest control, but the number of larvae has not declined in the Yoyogi Park, although that of imagoes has been relatively suppressed. Conclusion The 2014 outbreak emerged without particularly favorable climate conditions for vector mosquitoes. We found no obvious associations between the number of travelers or the imported dengue fever cases and the outbreak, but the increasing number of travelers may contribute to another outbreak. Pest control, including IGR, remains essential for infection control., Highlights • We studied 15 patients with autochthonous dengue fever during a local outbreak. • This outbreak emerged without favorable climate conditions for mosquitoes. • There were no increased number of travelers or imported dengue cases. • Pest control using insect growth regulator can be effective for infection control.

Objectives Japan’s healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer. Methods We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis—Cohort 1: 2008–2010, Cohort 2: 2011–2014 and Cohort 3: 2015–2018—and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis. Results Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P Conclusions In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.

Background Coronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19. Methods We retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity. Results A total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p

Transbronchial lung cryobiopsy (TBLC) has been increasingly utilised to diagnose diffuse parenchymal lung diseases (DPLDs) and lung cancers; however, TBLC protocols have not yet been standardised and the rate of complications associated with this procedure vary widely. Therefore, this prospective multicentre observational study investigated the safety and utility of the TBLC technique in patients with diffuse and localised respiratory diseases. This study was conducted at multiple medical centres in Japan between July 2018 and April 2019. The study's primary end-point was the rate of severe or serious adverse events associated with TBLC. Adverse events included bronchial bleeding, pneumothorax, pneumonia, respiratory failure, and an acute exacerbation of interstitial pneumonia. Adverse events were graded according to severity. During the TBLC procedure, an endobronchial balloon catheter for bronchial blockade was used in all patients. Pathological confidence and quality of specimens were categorised into three groups. A total of 112 patients were included. Neither severe nor serious adverse events were identified; therefore, the primary end-point was met. Nineteen patients (17%) experienced no bronchial bleeding. Mild or moderate bronchial bleeding was identified in 67% and 16% of patients, respectively. Mild pneumothoraces were identified in four patients (3.6%). The safety profile in patients aged ≥75 years was not significantly different from younger patients. Definite or probable pathological diagnoses were made in 84.9% of patients. This TBLC protocol with routine use of an endobronchial balloon had an acceptable safety profile and diagnostic yield in patients, including elderly ones, with diffuse and localised respiratory diseases., This multicentre prospective study showed an acceptable safety profile and diagnostic yield for transbronchial cryobiopsy with routine use of an endobronchial balloon for patients with diffuse and localised respiratory diseases, including elderly patients https://bit.ly/2Vv8Gky