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Hisamitsu Omori,1 Noritaka Higashi,2 Takeshi Nawa,3 Toshiki Fukui,4 Toshihiko Kaise,5 Takeo Suzuki5 1Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan; 3Department of Internal Medicine, Hitachi General Hospital, Hitachi, Japan; 4Center for Preventive Medical Treatment, Olive Takamatsu Medical Clinic, Takamatsu, Japan; 5Japan Development Division, GlaxoSmithKline K.K., Tokyo, JapanCorrespondence: Toshihiko KaiseJapan Development Division, GlaxoSmithKline K.K., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, JapanTel +81 80 5927 9500Fax +81 3 4231 5993Email toshihiko.kaise@gsk.comPurpose: The purpose of this study was to estimate the prevalence of subjects with chronic cough and phlegm and describe their characteristics including the presence or absence of airflow limitation among the general population in Japan.Subjects and Methods: This was an observational cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited. The existence of chronic cough and phlegm, airflow limitation, and treatment for respiratory diseases were examined. Chronic cough and phlegm were defined as having both symptoms for at least 3 months of the year and for at least 2 consecutive years, or as receiving any treatment for chronic bronchitis at the time of recruitment. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) less than 0.7.Results: In a total of 22,293 subjects, 380 subjects (1.7%) had chronic cough and phlegm. Among these 380 subjects, 21.8% received treatment for a respiratory disease, and 11.6% had airflow limitation. Compared to subjects without both chronic cough and phlegm but with airflow limitation, subjects with chronic cough and phlegm without airflow limitation were younger, more likely to be current smokers (39.6%), and had higher total scores on a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Scores of CAT questions 1– 4 (cough, phlegm, chest tightness, breathlessness, respectively) were higher in subjects with chronic cough and phlegm regardless of airflow limitation.Conclusion: This study demonstrated that subjects identified to have chronic cough and phlegm in comprehensive health examination settings were symptomatic, while most of them did not receive any treatment for respiratory diseases and did not have airflow limitation. Screening subjects for chronic cough and phlegm in a comprehensive health examination followed by a detailed examination of screened subjects could be an effective approach for better management of chronic cough and phlegm. Smoking cessation should be included in the management, in consideration that around 40% of subjects with chronic cough and phlegm were current smokers.Keywords: respiratory disease, chronic bronchitis, spirometry, lung function, general population, health checkup

A partial replacement of Portland cement (PC) by ground granulated blast furnace slag (GGBFS) is an effective method to improve the durability of concrete due to its lower diffusivity and higher chemical resistance compared to PC. Further, the microstructure of GGBFS blended cementitious materials controls the physicochemical properties and performance of the materials in concrete. Therefore, understanding of cement hydration and cementing behavior of GGBFS is essential to establish microstructure property relationship for predicting performance. In this study, hydration, microstructure development, and chloride ingress into GGBFS-blended cement have been investigated. Solid-phase assemblage and pore solution chemistry of hydrating PC and cement blended with GGBFS were predicted using thermodynamic model and compared with experimental data. A mathematical model integrating PC hydration, GGBFS reaction, thermodynamic equilibrium between hydration products and pore solution, ionic adsorption on C-S-H, multi-component diffusion, and microstructural changes was developed to predict chloride ingress into GGBFS blended cementitious materials. The simulation results on chloride profiles for hydrated slag cement paste, which was prepared with 50% of replacement of PC with GGBFS, were compared with experimental results. The model quantitively predicts the states of chloride such as free, adsorbed on C-S-H, and chemically bound as Friedel’s salt.

Background: Accidental hypothermia (AH) is a major cause of death in mountainous areas globally, and the second highest of mountaineering deaths in Japan, accounting for 37 % in Hokkaido. Managing AH is a significant challenge, particularly when adverse weather complicates the application of recommended rewarming and rapid transfer. To address this, the Hokkaido Police Organization (DOKEI) AH protocol was applied in Hokkaido's remote areas from 2011 to 2022, integrating high-temperature active external rewarming (HT-AER) with on-site sustained treatment., Methods: This study retrospectively analyzed the rescue reports and hospital records of hypothermia patients treated postprotocol, excluding patients with cold exposure, undetectable vital signs at rescue, and inadequate documentation. Protocol adherence and outcomes-hypothermia stage, cardiocirculatory collapse, survival, and neurological status-were assessed., Results: Among the 60 protocol-treated patients (19-74 years, 85 % male), 14 had stage 2 hypothermia, and 3 had stage 3 hypothermia. HT-AER was applied in 96.7 % of the patients. A total of 98.3 % of patients improved before handover without cardiac arrest (CA) or extracorporeal life support (ECLS). Comparatively, ten preprotocol patients (18-60 years, 70 % male) had two CAs, one fatal and six with no improvement., Conclusion: The DOKEI AH protocol demonstrates feasibility in managing stages 1-3 hypothermia, enhancing survival and neurological recovery, and can offer a vital option in challenging AH rescue scenarios., Competing Interests: Declaration of competing interest The authors declare 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(s). Published by Elsevier Inc. All rights reserved.)

Background: Quick arterial cannulation is required in pediatric emergency situation, which require effective local anesthesia to avoid withdrawal movement. However, pediatric local anesthesia could be difficult because of withdrawal movement. Jet injectors, which are needleless and provide local anesthesia quickly, could be helpful for pediatric local anesthesia during arterial cannulation., Aims: This study aimed to examine whether new jet injector "INJEX50" could improve the success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with the current standard of care, infiltration using a 26-gauge needle., Methods: This study was a randomized, double-blind, single-center study. Participants were infants and young children in the pediatric intensive care unit, who required an arterial line. Local anesthesia was performed with either a 26-gauge needle (group C) or INJEX50 (group I) before arterial cannulation. The primary outcome (success of local anesthesia) was the presence of withdrawal movement at the time of skin puncture for arterial cannulation. The secondary outcomes included rescue sedation during arterial cannulation. Data were analyzed using Fisher's exact test and the Mann-Whitney U-test, with values of p < .05 considered statistically significant., Results: Seventy patients were randomly assigned to groups C and I. The local anesthesia success rate in group I (30/35 [86%]) was significantly higher than that in group C (15/35 [43%], odds ratio, 8.00; 95% confidence interval, 2.51-25.5; p = .0005). In conclusion, INJEX50 could improve success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with 26-gauge needle., (© 2024 John Wiley & Sons Ltd.)

Human adenovirus (HAdV) infections present diverse clinical manifestations upon infecting individuals, with respiratory infections predominating in children. We surveyed pediatric hospitalizations due to respiratory HAdV infections across 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to March 2024, recording 473 admissions. While hospitalizations remained below five cases per week from July 2019 to September 2023, a notable surge occurred in late October 2023, with weekly admissions peaking at 15-20 cases from November to December. There were dramatic shifts in the age distribution of hospitalized patients: during 2019-2021, 1-year-old infants and children aged 3-6 years represented 51.4%-54.8% and 4.1%-13.3%, respectively; however, in 2023-2024, while 1-year-old infants represented 19.0%-20.1%, the proportion of children aged 3-6 years increased to 46.2%-50.0%. Understanding the emergence of significant outbreaks of respiratory HAdV infections and the substantial changes in the age distribution of hospitalized cases necessitates further investigation into the circulating types of HAdV in Hokkaido Prefecture and changes in children's neutralizing antibody titers against HAdV., (© 2024 Wiley Periodicals LLC.)

The treatment efficiency and predictors of atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma in real-world practice have not been established. This study aimed to assess the efficacy and safety of atezolizumab plus bevacizumab and to investigate predictors of progression-free survival and overall survival. Patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab therapy in 19 hospitals were enrolled before treatment and observed prospectively. The outcomes of 222 patients in this cohort were analyzed. The objective response rate and disease control rate were 22.0% and 70.6%, respectively, whereas the median progression-free survival was 5.7 months. Independent risk factors for shortened progression-free survival were younger age (<75 years; 3.9 months vs. 8.6 months), higher number of intrahepatic tumors (≥5; 4.0 months vs. 7.9 months), macrovascular invasion (2.3 months vs. 6.7 months), and higher neutrophil-to-lymphocyte ratio (≥3.03; 3.0 months vs. 7.8 months). The median overall survival was not reached; however, independent risk factors for shortened overall survival were absence of hyperlipidemia, higher number of intrahepatic tumors (≥5), macrovascular invasion, higher α-fetoprotein level (≥400 ng/mL), worse Child-Pugh score (≥6), and higher neutrophil-to-lymphocyte ratio (≥3.03). Severe adverse events (grade ≥3) were observed in 96 patients (36.0%), with proteinuria being the most frequent. In conclusion, patients with older age, lower number of intrahepatic tumors, absent macrovascular invasion, and lower neutrophil-to-lymphocyte ratio are expected to have better progression-free survival with atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Tetsuo Takehara has received lecture fees and research grants from Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd. Takahiro Kodama has received lecture fees from Chugai Pharmaceutical Co., Ltd and AstraZeneca K.K. All other authors declare no conflicts of interest., (Copyright: © 2024 Kai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Following the coronavirus disease 2019 (COVID-19) outbreak in February 2020, incidences of various infectious diseases decreased notably in Hokkaido Prefecture, Japan. However, Japan began gradually easing COVID-19 infection control measures in 2022. Here, we conducted a survey of children hospitalized with human metapneumovirus (hMPV), influenza A and B, and respiratory syncytial virus infections in 18 hospitals across Hokkaido Prefecture, Japan, spanning from July 2019 to June 2023. From March 2020 to June 2022 (28 months), only 13 patients were hospitalized with hMPV, and two patients had influenza A. However, in October to November 2022, there was a re-emergence of hMPV infections, with a maximum of 27 hospitalizations per week. From July 2022 to June 2023 (12 months), the number of hMPV-related hospitalizations dramatically increased to 317 patients, with the majority aged 3-6 years (38.2%, [121/317]). Influenza A also showed an increase from December 2022, with a peak of 13 hospitalizations per week in March 2023, considerably fewer than the pre-COVID-19 outbreak in December 2019, when rates reached 45 hospitalizations per week. These findings suggest the possibility of observing more resurgences in infectious diseases in Japan after 2023 if infection control measures continue to be relaxed. Caution is needed in managing potential outbreaks., (© 2023 Wiley Periodicals LLC.)

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions., (© 2023. The Author(s).)

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension., (© 2023. Springer Nature Limited.)

Background: Many reports have reported a reduction in respiratory infectious diseases and infectious gastroenteritis immediately after the coronavirus disease 2019 (COVID-19) pandemic, but data continuing into 2022 are very limited. We sought to understand the current situation of various infectious diseases among children in Japan as of July 2022 to improve public health in the post-COVID-19 era., Methods: We collected data on children hospitalized with infectious diseases in 18 hospitals in Japan from July 2019 to June 2022., Results: In total, 3417 patients were hospitalized during the study period. Respiratory syncytial virus decreased drastically after COVID-19 spread in early 2020, and few patients were hospitalized for it from April 2020 to March 2021. However, an unexpected out-of-season re-emergence of respiratory syncytial virus was observed in August 2021 (50 patients per week), particularly prominent among older children 3-6 years old. A large epidemic of delayed norovirus gastroenteritis was observed in April 2021, suggesting that the nonpharmaceutical interventions for COVID-19 are less effective against norovirus. However, influenza, human metapneumovirus, Mycoplasma pneumoniae , and rotavirus gastroenteritis were rarely seen for more than 2 years., Conclusions: The incidence patterns of various infectious diseases in Japan have changed markedly since the beginning of the COVID-19 pandemic to the present. The epidemic pattern in the post-COVID-19 era is unpredictable and will require continued careful surveillance., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries., Methods: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis., Results: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates., Conclusions: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Introduction: Individuals with neurodevelopmental disorders, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders (SLD) have various types of sensory characteristics., Methods: This study investigated sensory issues in individuals with neurodevelopmental disorders using a web-based questionnaire for qualitative and quantitative analysis, categorized the contents of their three most distressful sensory issues, and evaluated their order of priority., Results: Auditory problems were reported as the most distressing sensory issue among the participants. In addition to auditory problems, individuals with ASD frequently reported more tactile problems, and individuals with SLD reported more visual problems. Among the individual sensory issues, in addition to aversion to sudden, strong, or specific stimuli, some participants reported confusions regarding multiple stimuli presenting concurrently. Additionally, the sensory issues related to foods (i.e., taste) was relatively more common in the minor group., Conclusion: These results suggest that the diversity of sensory issues experienced should be carefully considered when aiding persons with neurodevelopmental disorders., Competing Interests: The 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 © 2023 Wada, Hayashi, Seino, Ishii, Nawa and Nishimaki.)

Aim: Alterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab., Methods: This study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts. Nineteen patients who received prior ATB were included in the ATB (+) group; 86 patients who did not receive prior ATB were included in the ATB (-) group. The therapeutic outcomes were compared between the two groups., Results: Most of the patients' baseline characteristics were not significantly different between the two groups. The objective response rates according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (30.1% vs. 11.1%; p = 0.143) and modified RECIST (mRECIST) (44.6% vs. 27.8%; p = 0.190) were not significantly different between the ATB (-) and ATB (+) groups. The disease control rates were higher in the ATB (-) group than in the ATB (+) group according to RECIST v1.1 (74.7% vs. 44.4%; p = 0.012) and mRECIST (78.3% vs. 50.0%; p = 0.020). Prior ATB use was found to be independently associated with radiological progressive disease of the first therapeutic assessment. The median progression-free survival according to RECIST v1.1 (9.1 months vs. 3.0 months; p = 0.049) and mRECIST (9.1 months vs. 3.0 months; p = 0.036), and overall survival (not reached vs. 11.4 months; p = 0.015) were longer in the ATB (-) group than in the ATB (+) group., Conclusions: Prior ATB use was associated with reduced therapeutic responses in patients with HCC receiving atezolizumab plus bevacizumab., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Professor Tetsuo Takehara has received research grants and lecture fees from Chugai Pharmaceutical Co., Ltd. All other authors declare no conflict of interest., (Copyright: © 2023 Maesaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A man in his 60s had end-stage alcoholic cirrhosis. About six months before his death, hepatic peribiliary cysts (HPBC) rapidly increased, and he developed jaundice and liver failure. The pathological autopsy performed after his death revealed that his intrahepatic bile duct was pressured due to multiple cysts caused by HPBC, which resulted in liver failure. Some cases of HPBC have been associated with alcoholic cirrhosis;however, no other cases of increased HPBC in a short period of time have been reported. Although identifying the cause of increased HPBC in a short time is difficult in this case, it may be have been caused by continuous alcohol drinking after the onset of HPBC. Most patients with HPBC have liver cirrhosis and obstructive jaundice that may promote liver failure as in this case. Therefore, patients with HPBC should not only be instructed for abstinence but also promptly consider effective treatments in the event of obstructive jaundice to prevent liver dysfunction.

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.

An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.

Background: Bifidobacterium breve is widely used as a probiotic in preterm infants and children with congenital surgical conditions, however, some cases of probiotics-induced bacteremia have been reported recently., Objectives: To examine the clinical and bacteriologic features of Bifidobacterium breve bacteremia caused by a probiotic (BBG-01) in term and preterm infants., Methods: We included 298 patients who were admitted to the neonatal intensive care unit of Miyagi Children's Hospital and were given BBG-01 as a probiotic within the period June 2014 to February 2019. We experienced six cases of B. breve bacteremia and assessed their features retrospectively., Results: The incidence rate of B. breve bacteremia in our hospital was 2% (6/298), higher than reported previously. The median age at onset, corrected age, and weight of the patients was 8 days (range: 5-27 days), 35 weeks (range: 26-39 weeks), and 1,940 g (range: 369-2734 g), respectively. The bacteremia triggers were gastrointestinal perforations in two cases, food protein-induced enterocolitis syndrome in two cases, adhesive ileus in one case, ileal volvulus in one case, and aspiration pneumonia following esophageal atresia repair in one case. B. breve was detected on blood cultures after a median of 5 days 13 hours (range: 4 days 18 hours-9 days 13 hours). No patient demonstrated serious symptoms, such as septic shock. All patients received antibiotics and recovered without any sequelae., Conclusions: Ileus and intestinal mucosal damage, such as enteritis, can cause B. breve bacteremia. The incidence of B. breve bacteremia may be higher than reported previously and detection via culture may require a longer time than typically needed for more common bacteria. It is associated with a good prognosis., Competing Interests: The authors declare no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The epidemic of coronavirus disease 2019 (COVID-19) rapidly spread worldwide, and the various infection control measures have a significant influence on the spread of many infectious diseases. However, there have been no multicenter studies on how the number of hospitalized children with various infectious diseases changed before and after the outbreak of COVID-19 in Japan., Methods: We conducted a multicenter, prospective survey for hospitalized pediatric patients in 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to February 2021. We defined July 2019 to February 2020 as pre-COVID-19, and July 2020 to February 2021 as post-COVID-19. We surveyed various infectious diseases by sex and age., Results: In total, 5300 patients were hospitalized during the study period. The number of patients decreased from 4266 in the pre-COVID-19 period to 701 (16.4%) post-COVID-19. Patients with influenza and RSV decreased from 308 to 795 pre-COVID-19 to zero and three (0.4%) post-COVID-19. However, patients with adenovirus (respiratory infection) only decreased to 60.9% (46-28) of pre-COVID levels. Patients with rotavirus, norovirus, and adenovirus gastroenteritis decreased markedly post-COVID-19 to 2.6% (38-1), 27.8% (97-27) and 13.5% (37-5). The number of patients with UTIs was similar across the two periods (109 and 90). KD patients decreased to 31.7% (161-51) post-COVID-19., Conclusions: We suggest that current infection control measures for COVID-19 such as wearing masks, washing hands, and disinfecting hands with alcohol are effective against various infectious diseases. However, these effects vary by disease., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Recent studies, using magnetic resonance imaging (MRI) to assess white matter injury in preterm brains, increasingly recognize punctate white matter lesions (PWML) as the primary lesion type. There are some papers showing the relationship between the size and number of PWML and the prognosis of infants. However, the histopathological features are still unknown. In this study, we experimentally induced periventricular leukomalacia (PVL) in a sheep fetus model, aiming to find whether MRI can visualize necrotic foci (small incipient lesions of PVL) as PWML. Three antenatal insults were employed to induce PVL in preterm fetuses at gestational day 101-117: (i) hypoxia under intrauterine inflammation, (ii) restriction of artificial placental blood flow, and (iii) restriction of artificial placental blood flow after exposure to intrauterine inflammation. MRI was performed 3-5 days after the insults, and standard histological studies of the PVL validated its findings. Of the 89 necrotic foci detected in histological samples from nine fetuses with PVL, 78 were visualized as PWML. Four of the lesions detected as abnormal findings on MRI could not be histologically detected as corresponding abnormal findings. The diagnostic sensitivity and positive predictive values of histologic focal necrosis visualized as PWML were 0.92 and 0.95, respectively. The four lesions were excluded from these analyses. These data suggest that MRI can visualize PVL necrotic foci as PWML 3-5 days after the injury induction. PWML can spontaneously become obscure with time after birth, so their accurate diagnosis in the acute phase can prevent overlooking mild PVL.

Background: Indium is a metal used as a compound called indium-tin oxide for liquid crystal display. Its inhalation causes lung toxicity, resulting in a new occupational lung disease called indium lung. Although the carcinogenicity of indium has been reported in an animal model, its carcinogenicity in humans is unknown., Case Presentation: This is the first reported case of a primary lung cancer originating from indium lung. In this report, we describe a 46-year-old man with interstitial pneumonia-type indium lung diagnosed 16 years ago. The initial symptom was left chest pain, and computed tomography showed a mass adjacent to the aorta with left pleural effusion. Specimens collected using video-assisted thoracoscopy revealed an adenocarcinoma with a high expression of programmed cell death-ligand 1 (cT4N0M1a stage IVA). Although the lesions showed a remarkable aggressive nature, the patient benefited from pembrolizumab, a monoclonal antibody against programmed cell death 1, which was used as second-line therapy for 2 years., Conclusions: It is important for clinicians to be aware of lung cancer development in indium-exposed workers or in patients with indium lung, as this could have an aggressive behavior. Treatment with immune checkpoint inhibitors is an option even in patients with interstitial pneumonia-type indium lung.

Purpose: To identify associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases in health examinees, and to describe the characteristics of each subgroup classified by comorbidities., Subjects and Methods: This was an observational cross-sectional survey carried out in multiple regions of Japan. Subjects aged 40 years older, undergoing comprehensive health examination, were recruited. Airflow limitation was defined as having forced expiratory volume in 1 s/forced vital capacity lower than 70%. Associated factors of having at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases were examined by logistic regression analysis. Subgroup classification by comorbidity patterns was conducted by hierarchical cluster analysis., Results: In a total of 22,293 subjects, 1520 (6.8%) had at least one of the airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases. With this objective variable, the following explanatory variables were significantly associated: older age, higher total score in the chronic obstructive pulmonary disease assessment test (CAT) and coexistence of lung cancer (common in ever-smokers and never-smokers), higher pack-years, lower body mass index, higher C-reactive protein, without coexistence of diabetes mellitus (specific in ever-smokers), male sex, coexistence of anxiety, and sleep disorder (specific in never-smokers). Among the 1520 subjects, 1512 subjects with smoking history data were classified by comorbidity patterns into subgroups of "no comorbidities," "mixed comorbidities," "inflammatory comorbidities," "overweight," "underweight," and "chronic kidney disease." "Inflammatory comorbidities" were specific in ever-smokers, and "underweight" was specific in never-smokers., Conclusion: Several factors were identified as associated factors of having at least one of airflow limitation, chronic cough/phlegm, and currently treated respiratory diseases and they were different between ever-smokers and never-smokers. Different comorbidity patterns were observed by smoking history. These findings could provide information to assist the management of subjects with COPD or at risk for COPD in the general population., Competing Interests: GlaxoSmithKline (GSK) was the funding source and was involved in all stages of this study (WEUSKOP6290). GSK also funded all costs associated with the publishing of the present manuscript. HO, NH, TN, and TF received funding for this study from GSK. TK is an employee of GSK and owns stock of the company; receives pay for part-time lecture from Shiga University of Medical Science. TS is an employee of GSK. The authors report no other potential conflicts of interest for this work., (© 2020 Omori et al.)

Shrinkage-reducing agents have been developed to mitigate shrinkage and to control cracks in concrete. This study aims to evaluate the impact of a newly developed shrinkage-reducing agent (N-SRA) on concrete properties and to compare its properties with a conventional shrinkage-reducing agent (C-SRA). The hydration rate, compressive strength, splitting tensile strength, shrinkage, occurrence of cracking, and freezing and thawing were investigated. N-SRA showed higher surface tension than C-SRA and reduced shrinkage to the same degree as C-SRA with half the dosage of C-SRA. The addition of N-SRA or C-SRA did not influence the early compressive strength but slightly reduced splitting tensile strength at seven days. Concrete with N-SRA showed higher compressive strength at 28 days than those of concrete with C-SRA or without SRA. Furthermore, concrete with N-SRA extended the period for the occurrence of shrinkage cracking under restrained conditions. It was found that N-SRA provided excellent freezing and thawing resistance because of the formation of good air voids, while C-SRA demonstrated inefficient behaviour in such an environment.

Background and study aims  The best method for endoscopic placement of self-expandable metallic stents (SEMS) for distal malignant biliary obstruction (MBO) has not yet been determined. The aim of this study was to evaluate how SEMS placement above the papilla and without endoscopic sphincterotomy (EST) impacts the time to recurrent biliary obstruction (RBO) in patients with distal MBO. Patients and methods  We retrospectively reviewed data for 73 consecutive patients with unresectable distal MBO who underwent endoscopic SEMS placement for the first time at our institution between April 2014 and March 2016. We compared time to RBO of SEMS placement above the papilla (intraductal placement) with SEMS placement across the papilla (transpapillary placement). In the intraductal placement group, we also compared time to RBO of placement without EST with placement with EST. Results  Endoscopic SEMS placement was performed in 30 patients with intraductal placement and in 43 patients with transpapillary placement. The median time to RBO was significantly longer with intraductal placement (307 days) than with transpapillary placement (161 days) ( P  = 0.022). Complication rates did not differ between the two groups. In both univariate and multivariate analysis, intraductal placement was an independent factor contributing to prolonged time to RBO. In intraductal placement, time to RBO was significantly longer in SEMS placement without EST than with EST (363 days vs. 227 days, respectively; P  = 0.026). Conclusions  Intraductal SEMS placement, especially without EST for distal MBO contributed to longer time to RBO., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Aims: Although distinct DNA methylation patterns have been reported, its localization and roles remain to be defined in heart failure. We investigated the cellular and subcellular localization of DNA methylation and its pathophysiological significance in human failing hearts., Methods and Results: Using left ventricular (LV) endomyocardial biopsy specimens from 75 patients with dilated cardiomyopathy (DCM; age: 58 ± 14 years old, %female: 32%) and 20 patients without heart failure (controls; age: 56 ± 17 years old, %female: 45%), we performed immunohistochemistry and immunoelectron microscopy for methylated DNA, 5-methylcytosine (5-mC). We next investigated possible relations of the incidence of 5-mC-positive (%5-mC + ) cardiomyocytes with clinicopathological parameters. Immunopositivity for 5-mC was detected in the cardiomyocytes and other cell types. The %5-mC + cardiomyocytes was significantly greater in DCM hearts than in controls (57 ± 13% in DCM vs. 25 ± 12% in controls, P < 0.0001). The localization of 5-mC immunopositivity in cardiomyocyte nuclei coincided well with that of heterochromatin, as confirmed by immunoelectron microscopy. Substantial DNA methylation was also observed in interstitial non-cardiomyocytes, but the incidences did not differ between control and DCM hearts (39 ± 7.9% in DCM vs. 41 ± 10% in controls, P = 0.4099). In DCM patients, the %5-mC + cardiomyocytes showed a significant inverse correlation with LV functional parameters such as heart rate (r = 0.2391, P = 0.0388), end-diastolic pressure (r = 0.2397, P = 0.0397), and ejection fraction (r = -0.2917, P = 0.0111) and a positive correlation with LV dilatation (volume index at diastole; r = 0.2442, P = 0.0347; and volume index at systole; r = 0.3136, P = 0.0062) and LV hypertrophy (mass index; r = 0.2287, P = 0.0484)-that is, LV remodelling parameters. No significant correlations between DNA methylation and the histological parameters of the biopsies, including cardiomyocyte hypertrophy, fibrosis, and inflammatory cell infiltration, were noted., Conclusions: The present study revealed increased nuclear DNA methylation in cardiomyocytes, but not other cell types, from DCM hearts, with predominant localization in the heterochromatin. Its significant relations with LV functional and remodelling parameters imply a pathophysiological significance of DNA methylation in heart failure., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Tyrosine kinase inhibitors (TKIs) are widely used for systemic chemotherapy of hepatocellular carcinoma (HCC). Arterial thromboembolism (ATE) has been reported to be an adverse event associated with TKI therapy, but its incidence is rare. Here, we report a case of an HCC patient who developed a thrombus in the superior mesenteric artery (SMA) while on TKI therapy. The patient was a 78-year-old Japanese man with hepatitis C virus-associated HCC with multiple nodules. Several sessions of transarterial chemoembolization therapy caused him to become refractory to the treatment. Sorafenib and regorafenib therapy had also been previously performed, but his disease continued to progress gradually. Therefore, we started lenvatinib therapy. When a contrast-enhanced computed tomography (CT) examination was performed 2 months later, we found a thrombus in the SMA. Retrospective analysis of the CT images revealed that the thrombus formed during the sorafenib-regorafenib sequential therapy and it developed rapidly, especially during the lenvatinib therapy. An HCC patient developed a thrombus in the SMA during TKI therapy. The incidence of ATE is rare in TKI treatment; however, long-term or sequential TKI therapy may increase the frequency of ATE. Further study is needed.

We have developed a metallic micro-cavity array filter and an automated detection system for capturing circulating tumor cells (CTCs). In this single institutional pilot study, we assessed the ability of this device to detect CTCs in patients with lung cancer at each stage. Patients diagnosed with lung cancer, undergoing planned surgery for lung cancer, or suspected of having lung cancer were recruited (40 recruited and 2 excluded). Blood samples were obtained from the patients and 3 ml whole blood was applied to the device without any preparation. The captured cells were stained to differentiate the nucleus, and determine cytokeratin and CD45 expression. Subsequently, two operators blinded to clinical information counted the number of CTCs. Sample collection was performed at the time of recruitment, before treatment and ~3 months after initial blood collection. CTC counts at recruitment were 1.4±0.4, 1.8±1.2, 1.3±0.6 and 7.4±5.1 (mean ± SE) in clinical stages I, II, III and IV, respectively. No significant difference was observed among the stages. These data indicated the ability of this device to detect CTCs at early or non-metastatic stages of lung cancer. Further research on a larger scale is needed for a more accurate assessment of the device, and research on the utility of captured cells remains a future challenge., (Copyright © 2019, Spandidos Publications.)