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The propagation and transformation of multi-directional and uni-directional random waves over a coast with complicated bathymetric and geometric features are studied experimentally and numerically. Laboratory investigation indicates that wave energy convergence and divergence cause strong coastal currents to develop and inversely modify the wave fields. A coastal spectral wave model, based on the wave action balance equation with diffraction effect (WABED), is used to simulate the transformation of random waves over the complicated bathymetry. The diffraction effect in the wave model is derived from a parabolic approximation of wave theory, and the mean energy dissipation rate per unit horizontal area due to wave breaking is parameterized by the bore-based formulation with a breaker index of 0.73. The numerically simulated wave field without considering coastal currents is different from that of experiments, whereas model results considering currents clearly reproduce the intensification of wave height in front of concave shorelines.

Key Clinical Message: In addition to the reentrant map, the wave speed map can be helpful in accurately identifying the CTI gap during radiofrequency application for atrial flutter(AFL). However, in complex cases involving extensive scarring and multiple low-velocity local areas, this technique may not be useful., Abstract: A 73-year-old male patient with a history of pulmonary vein isolation and cavotricuspid isthmus ablation underwent a second catheter ablation owing to recurrent atrial flutter (AFL). The AFL was diagnosed as cavotricuspid isthmus-dependent AFL caused by the reconnection of the previous cavotricuspid isthmus ablation. Wave speed mapping was performed at the same site, and results comprehensively revealed a low-velocity local area. The AFL was terminated after the first radiofrequency application, and the block line was easily completed. Therefore, this technique could be an adjunctive tool for cavotricuspid isthmus gap identification and minimal radiofrequency application., Competing Interests: All authors have no conflicts of interest to disclose., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Hospital-based specialized palliative care teams (HSPC) are important for symptom management and ethics support, especially during complex decision-making, but the needs of patients with noncancer diseases and their families from the HSPC are unclear. This study aimed to (I) compare the prevalence of symptom between patients with and without cancer and explore changes in symptom intensity after HSPC consultation in patients with noncancer; (II) determine factors related to ethics support; and (III) compare the percentage of request contents from patients and their families when a certified nurse specialist in gerontological nursing (geriatric care nurse below) is present in the HSPC to that when a certified nurse specialist in palliative care (palliative care nurse below) is present in the HSPC., Methods: We utilized a retrospective cohort study to analyze 761 patients (360 with noncancer and 401 with cancer) referred to our HSPC at the National Center for Geriatrics and Gerontology using 10-year data (since 2011) available in an electronic medical record database. (I) Symptom scores of the Support Team Assessment Schedule were compared between noncancer and cancer groups and between initial and 1-week assessments for noncancer patients. (II) Ethics support was compared between noncancer (including dementia) and cancer. The presence or absence of ethics support requests, which was set as the objective variable, was examined using logistic regression analysis. (III) The percentage of request contents selected from nine items defaulted on the electronic medical record when a geriatric care nurse was present in our HSPC were compared to those when a palliative care nurse was present in our HSPC., Results: Compared to those with cancer, patients with noncancer suffered more from dyspnea and sputum accumulation. More than 10% of patients with noncancer had suffered from pain, dyspnea, sputum accumulation, and anorexia that required treatment, with symptom scores showing improvement after 1 week of HSPC involvement, except for the sputum accumulation. Moreover, for anorexia, symptom scores improved, but >10% of these patients continued to suffer. Patients with noncancer diseases, including dementia, received ethics support than those with cancer without dementia. More requests for ethics support were received when a geriatric care nurse was in the HSPC than when a palliative care nurse was in the HSPC. Logistic regression analysis revealed that requests for ethics support were more frequent from patients or families with impaired decision-making capacity or when the patient lacked an advocate., Conclusions: The needs of patients with noncancer diseases and families from the HSPC in Japan included (I) symptom management for intractable conditions, such as sputum accumulation; (II) ethics support for patients with noncancer diseases, including dementia, with impaired decision-making capacity, and without advocates; and (III) advice on ethics issues from a geriatric care nurse.

Background/aim: Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients., Patients and Methods: Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores., Results: Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×10 3 /μl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients., Conclusion: Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Symptoms of catatonia include silence, motionlessness, and postural retention. Although it is important to detect and treat catatonia early, before it becomes severe, postoperative cases have inherent risks that hinder diagnosis and treatment. A 60-year-old man with schizophrenia underwent endoscopic/thoracoscopic esophagectomy and was extubated in the operating room. In the intensive care unit (ICU), he had stiffness in the neck, ankles, and knees, catalepsy during passive knee flexion, mild disturbance of consciousness, mild creatine kinase elevation, and respiratory depression. Intravenous diazepam was administered for diagnosis, and the patient's rapid improvement indicated catatonia. He was intubated and started on lorazepam; tapering produced no recurrence of symptoms. The patient was extubated and transferred to the general ward on postoperative Day 2. Because this patient was extubated in the operating room and was managed postoperatively in the ICU with a full-time doctor, his symptoms were easily recognized and early diagnosis was possible. Thus, we were able to administer drug therapy quickly and adequately and perform forward management that accounted for postoperative risks, thereby achieving a favorable outcome.

In Japan, use of a report for providing information from pharmacies to medical institutions called as "tracing report (TR)" is not widespread especially in the field of cancer chemotherapy. Identification of the factors related to submission of TRs could enhance the necessity of TRs. The purpose of this study is to clarify the factors related to submission of TRs regarding cancer chemotherapy through a questionnaire survey. A questionnaire survey was conducted at the live web-based seminar regarding cancer chemotherapy held for pharmacists in January 2023. After the questionnaire survey, the participants were divided into those who had submitted at least one TR regarding cancer chemotherapy within one month before the seminar (TR group) and those who had not (non-TR group). The multivariate analysis was conducted to identify factors related to submission of TRs regarding cancer chemotherapy. Of 118 participants, the responses from 93 pharmacy pharmacists involved in dispensing drugs who agreed to participate in this study and fulfilled all questionnaire were analyzed. TR group included 21 participants and non-TR group included 72. As a result of multivariate analysis, "Years of experience in counseling and following-up with patients undergoing cancer chemotherapy (odds ratio: 4.81, p=0.02)" and "Types of workplaces (odds ratio: 3.79, p=0.02)" significantly increased the incidence of submission of TRs regarding cancer chemotherapy. It was revealed that experience of intervention in cancer chemotherapy cases and an environment in which prescriptions for cancer chemotherapy can be handled on a daily basis are important for submission of TRs regarding cancer chemotherapy.

Introduction: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes., Methods and Analysis: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results., Ethics and Dissemination: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals., Trial Registration Number: UMIN000047023., Competing Interests: Competing interests: The following authors have potential conflicts of interest: YO received research funding from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Pfizer and Boston Scientific Japan, and accepted remuneration from Bayer Healthcare, Daiichi-Sankyo and Bristol-Meyers Squibb. KNas accepted remuneration from Johnson & Johnson K.K. TK received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Bayer Healthcare, Boston Scientific and Medtronic Japan. HF accepted remuneration from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Abbott Medical Japan, Medtronic Japan and Japan Lifeline. SN received speaker honoraria from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb and Medtronic Japan. WS received grants from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim; and remuneration for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi Sankyo, Nippon Boehringer Ingelheim, Bristol-Meyers Squibb, K.K., Bayer Yakuhin, Pfizer, Ono Pharmaceutical and Medtronic Japan. YM received lecture fees from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Japan Lifeline K.K, Medtronic Japan, Pfizer and Boston Scientific Japan. SSu received research funding from Daiichi Sankyo and remuneration from Bristol-Myers Squibb and Daiichi Sankyo. MHar received research funding from BIOTRONIK Japan, Medtronic Japan, Abbott Japan, Japan Lifeline, Nihon Kohden and Boston Scientific Japan, and accepted remuneration from Nippon Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Meyers Squibb, Medtronic Japan, Japan Life Line and Abbott Japan. TY received speaker honoraria from Medtronic Japan and Abbott Medical Japan. MTo received research funding from Japan Lifeline and consulting fee from Medtronic Japan. MTa belongs to the Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine. This section supported by an endowment from Abbott Japan, Medtronic Japan and Boston Scientific Japan. MS is affiliated with an endowed division supported by BIOTRONIK Japan, Boston Scientific Japan K.K., Medtronic Japan and Abbott Medical Japan. AO taught courses endowed by BIOTRONIK, Abbott, Medtronic, Boston Scientific Japan and Japan Lifeline. KSa accepted remuneration from Abbott Japan, Medtronic Japan and Japan Lifeline. HKi accepted remuneration from Otsuka Pharmaceutical., AstraZeneca, Bristol-Meyers Squibb, Ono Pharmaceutical, Pfizer and Novo Nordisk. KMu received honoraria for Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, MSD, Kyowa Kirin, Yakult Pharmaceutical and Boehringer Ingelheim. KKus received speaker honoraria from Daiichi-Sankyo, Nippon Boehringer Ingelheim, Bayer Yakuhin, Pfizer and Medtronic Japan, and research grants from Medtronic Japan and JSR. KoM received speaker honoraria from Medtronic Japan and Abbott Japan, and research funding from Bristol-Meyers Squibb, Pfizer, Medtronic Japan, Japan Lifeline and Boston Scientific Japan., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Oxygenator exchange during extracorporeal membrane oxygenation (ECMO) is a life-threatening procedure. D-dimer has been used to predict oxygenator failure, but it is a parameter used a few days before oxygenator exchange. This study investigated parameters before and immediately after ECMO initiation that predict oxygenator exchange., Methods: This was a single-center, retrospective study of 28 patients who received veno-venous ECMO with heparin/silicone-coated polypropylene oxygenator (NSH-R HPO-23WH-C; Senko Medical Inc., Tokyo, Japan), due to acute respiratory failure, from April 2015 to March 2020. Clinical data before ECMO initiation and during the first 3 days on ECMO were compared between the patients with oxygenator exchange (exchange group) and those without oxygenator exchange (non-exchange group)., Results: Nine (32%) patients required oxygenator exchange. The exchange group had significantly higher white blood cell count (WBC) (16,944 ± 2423/µL vs 10,342 ± 1442/µL, p  < 0.05) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (31 ± 5 vs 25 ± 8, p  < 0.05) before ECMO initiation than the non-exchange group. The partial pressure of oxygen at the outlet of the oxygenator (PO 2 outlet ) and activated partial thromboplastin time (aPTT) during the first 3 days on ECMO were significantly lower in the exchange group than in the non-exchange group., Conclusions: High WBC and APACHE II score before ECMO initiation, low PO 2 outlet , and aPTT during the first 3 days on ECMO were associated with oxygenator exchange during veno-venous ECMO. These parameters could be used to avoid unexpected oxygenator exchange.

Objective: To investigate the effects of discontinuing antihypertensive drugs on the characteristics of patients with frailty syndrome., Methods: This prospective pilot study was conducted between March 2016 and July 2019. Among patients who visited the frailty clinic within this period, outpatients who received antihypertensive drugs at their first visit and were followed-up for about 1 year were enrolled. Participants who discontinued or continued antihypertensive drugs during 1 year of follow-up were classified into a discontinuation group or continuation group, respectively. Each domain in the Kihon checklist (KCL), fall risk score, short physical performance battery (SPPB) score, and skeletal muscle index (SMI) were assessed at the first visit and 1-year follow-up assessment, and were compared between the two groups., Results: Among 498 patients who attended the frailty clinic, 78 were enrolled (discontinuation group, n  = 19; continuation group, n  = 59). At the first visit, SMI scores were significantly higher in the discontinuation versus continuation group. At the 1-year assessment, physical strength in the KCL for the discontinuation group and various SPPB scores for both groups were significantly improved, and the fall risk score was improved in the continuation group., Conclusion: Discontinuation of antihypertensive drugs may positively affect physical performance.

A NIMA-related protein kinase, MpNEK1, directs tip growth of rhizoids through microtubule depolymerization in a liverwort Marchantia polymorpha . The Mp nek1 knockouts were shown to develop curly and spiral rhizoids due to the fluctuated direction of growth. Still, physiological roles and mechanisms of MpNEK1-dependent rhizoid tip growth remain to be clarified. Here, we developed novel culture methods to further study rhizoid growth of M. polymorpha , in which plants were grown on vertical plates. We applied the established methods to investigate MpNEK1 function in rhizoid growth. Rhizoids of the wild-type and Mp nek1 plants grew toward the gravity. The aerial rhizoids were longer in Mp nek1 than in the wild type. When the rhizoids were grown on the surface of a cellophane sheet, rhizoid length was comparable between the wild type and Mp nek1 , whereas Mp nek1 developed more rhizoids compared to the wild type. We also applied gellan gum, which is more transparent than agar, to analyze rhizoids grown in the medium. Rhizoids of Mp nek1 displayed defect on entering into the solid medium. These results suggest that Mp nek1 rhizoids have the deficiency in invasive tip growth. Thus, stable directional growth is important for rhizoids to get into the soil to anchor plant body and to adsorb water and nutrients. Collectively, our newly designed growth systems are valuable for analyzing rhizoid growth., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Backgrounds: An adverse increased risk of atrial fibrillation (AF) can be detected by measuring the p-wave indices, including prolonged p-wave duration, the PR interval, abnormal p-wave terminal force, and abnormal p-wave axis (aPWA). Our purpose was to characterize the AF patient population with an aPWA and to identify whether the aPWA was associated with recurrence after catheter ablation of AF., Methods: This study retrospectively included 249 patients with AF who underwent catheter ablation in our hospital from October 2015 to May 2019. We measured the p-wave indices and left atrial cavity size (LAVI) before the catheter ablation. A logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence of AF recurrence over 12 months after the ablation., Results: An aPWA was observed in 35 patients (14%). There were significantly more patients with an aPWA in the non-PAF than PAF patients (26% versus 7%, p < 0.001). The patients with an aPWA had a significantly larger LAVI values (37 ± 12 versus 45 ± 11 ml/m2, p = 0.016). In a multivariate analysis, an aPWA (odds ratio, 4.27; 95% confidence interval, 1.75-10.4; p = 0.001) and the LAVI (odds ratio, 1.04; 95% confidence interval, 1.00-1.08; p = 0.032) were independently associated with recurrence after catheter ablation., Conclusions: Our results demonstrated that measuring the aPWA in patients with atrial fibrillation before ablation was useful for identifying patients at a higher risk of recurrence after catheter ablation of AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Systematic reviews have identified effective strategies for increasing postal response rates to questionnaires; however, most studies have isolated single techniques, testing the effect of each one individually. Despite providing insight into explanatory mechanisms, this approach lacks ecological validity, given that multiple techniques are often combined in routine practice., Methods: We used a two-armed parallel randomised controlled trial (n = 2702), nested within a cross-sectional health survey study, to evaluate whether using a pragmatic combination of behavioural science and evidenced-based techniques (e.g., personalisation, social norms messaging) in a study invitation letter increased response to the survey, when compared with a standard invitation letter. Participants and outcome assessors were blinded to group assignment. We tested this in a sample of women testing positive for human papillomavirus (HPV) at cervical cancer screening in England., Results: Overall, 646 participants responded to the survey (response rate [RR] = 23.9%). Logistic regression revealed higher odds of response in the intervention arm (n = 357/1353, RR = 26.4%) compared with the control arm (n = 289/1349, RR = 21.4%), while adjusting for age, deprivation, clinical site, and clinical test result (aOR = 1.30, 95% CI: 1.09-1.55)., Conclusion: Applying easy-to-implement behavioural science and evidence-based methods to routine invitation letters improved postal response to a health-related survey, whilst adjusting for demographic characteristics. Our findings provide support for the pragmatic adoption of combined techniques in routine research to increase response to postal surveys., Trial Registration: ISRCTN, ISRCTN15113095 . Registered 7 May 2019 - retrospectively registered., (© 2021. The Author(s).)

The successful use of prolonged (ie, >28 days) veno-venous extracorporeal membrane oxygenation (V-V ECMO) is being increasingly reported. However, limited data are available on its outcomes. This study investigated the outcomes of acute respiratory distress syndrome (ARDS) patients on prolonged ECMO support. We retrospectively evaluated 57 patients requiring V-V ECMO for ARDS between 2015 and 2020. The patients were divided into two groups according to ECMO duration: (a) ≤28 days group (n = 43, 75%) or (b) >28 days (n = 14, 25%) group. Clinical characteristics, complications, and outcomes between these two groups were statistically compared. There were no significant differences in demographics, comorbidity, ARDS etiology, and severity scores between the two groups. However, the mechanical ventilation period before ECMO initiation was significantly longer in the >28 days group than in the ≤28 days group (10.5 days vs. 1 day; P < .05). The incidence of positive bacterial blood culture results during ECMO was significantly higher in the >28 days group than in the ≤28 days group (43% vs. 9%; P < .05). Additionally, the hospital survival rate was significantly lower in the >28 days group than in the ≤28 days ECMO group (21% vs. 60%; P < .05). Prolonged ECMO was associated with worse hospital survival outcomes. Early initiation of ECMO along with meticulous care and appropriate treatment against infection during ECMO could improve the hospital survival of ARDS patients on prolonged ECMO support., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known., Hypothesis: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs., Methods: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT., Results: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT., Conclusion: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July-September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowledged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016-2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted essential health services. Simultaneously, it has created opportunities for citizens to raise awareness of personal hygiene, mask wearing, and other preventive measures. This brief report aims to clarify the epidemiological trends of measles and rubella in Japan and to explore future challenges for controlling these diseases during and after the COVID-19 pandemic. Although Japan eliminated measles in 2015, the number of measles patients has gradually increased since then, and reached 744 in 2019. In the 2010s, Japan experienced two large rubella epidemics, and the majority of the patients were reported in Tokyo and other metropolitan areas. While the transmission of measles and rubella seems to be suppressed during the COVID-19 pandemic, closing the gap in routine childhood vaccination will be challenging in any country. Moreover, supplementary immunization campaigns for adults have also been disrupted, and they must be invigorated. While the pandemic has a devastating effect on a global scale, it should be utilized as a good opportunity to regain faith in vaccines, implement an evidence-based vaccination policy, and strengthen international cooperation.

Guanosine 5'-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-β-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability.

Intravascular lymphoma is a rare disease that progresses to multiple organ dysfunction caused primarily by tumor cell proliferation in small blood vessels. Few studies have investigated critical care management of intravascular lymphoma. We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived. A 64-year-old man with impaired consciousness was diagnosed as having intravascular large B-cell lymphoma by means of a random skin biopsy. The patient arrived at our hospital's intensive care unit (ICU) with impaired consciousness, respiratory failure that required mechanical ventilation, and lactic acidosis that required renal replacement therapy. Mechanical ventilation and renal replacement therapy were continued in the ICU, and his respiratory status and circulatory dynamics eventually stabilized. However, his impaired consciousness and hyperlactatemia did not improve until after the start of chemotherapy with doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab. Although he developed tumor lysis syndrome immediately after chemotherapy, his systemic condition was gradually stabilized by continued critical care management primarily comprising renal replacement therapy. He was weaned from ventilator support after a tracheotomy and moved to the general ward. Hematopoietic malignancy with hyperlactatemia has a very poor prognosis; however, hyperlactatemia and impaired consciousness were dramatically improved in this patient by critical care management and chemotherapy.

Background: Non-cardiac surgery for hypertrophic obstructive cardiomyopathy (HOCM) is considered to require meticulous perioperative care. β-blockers are considered the first-line drugs for patients with HOCM, and they play a key role in preventing cardiovascular complications in perioperative care. The bisoprolol transdermal patch has recently become available in Japan, and it is useful for patients who are unable to take oral medication during perioperative care. The aim of this case series was to assess the hemodynamic features of patients with HOCM who used the bisoprolol transdermal patch during perioperative care for non-cardiac surgery., Methods: Between August 2016 and August 2018, we retrospectively analyzed 10 consecutive cases of HOCM with the patients using the bisoprolol transdermal patch during perioperative care. Hemodynamic and echocardiographic features were evaluated before and after patients were switched from oral bisoprolol to transdermal patch therapy or started transdermal patch therapy as a new β-blocker medication. In addition, cardiovascular complications (all-cause death, cardiac death, heart failure, ventricular tachycardia, and ventricular fibrillation) during the perioperative period were evaluated., Results: There was no significant change in the patients' heart rate, blood pressure, ejection fraction, and pressure gradient in the left ventricle after switching from oral bisoprolol to the transdermal patch therapy. On the other hand, patients who started using the bisoprolol transdermal patch as a new ß-blocker medication tended to have a decreased heart rate and pressure gradient thereafter, but there was no significant difference in blood pressure or ejection fraction. No cardiovascular complications occurred during the perioperative period., Conclusions: We described the utilization of the bisoprolol transdermal patch during perioperative care for non-cardiac surgery in patients with HOCM. We determined that the hemodynamic features of these patients did not change significantly after switching to patch therapy. Further, initiation of the bisoprolol transdermal patch as a new ß-blocker medication sufficiently tended to decrease the pressure gradient. This unique approach can be an alternate treatment option for HOCM., Trial Registration: The registry was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036703). The date of registration was 10/5/2019 and it was "Retrospectively registered".

Background : Nivolumab efficacy in patients with non-small-cell lung cancer (NSCLC) and performance status (PS) of 2-4 is unclear. We aimed to compare survival, treatment efficacy, and safety in patients with NSCLC with poor PS who received nivolumab plus best supportive care (BSC) with those in patients who received BSC alone in a palliative care unit (PCU). Patients and methods : This retrospective study included 99 consecutive patients with NSCLC who received nivolumab plus BSC or BSC alone between December 2015 and March 2018. Results : In total, 43 patients with PS of 0-1 (good PS group) and 20 patients with PS of 2-4 (poor PS group) received nivolumab plus BSC; the remaining 36 patients received BSC alone in the PCU (PC group). Median overall survival was 32 days [95% confidence interval (CI), 21-43] in the poor PS group and 31 days (95% CI, 25-37) in the PC group (hazard ratio, 0.653; 95% CI, 0.368-1.158; P = 0.137). Moreover, median overall survival in patients with PS of 3 or 4 among the poor PS group was not significantly longer than that in the PC group (HR, 1.235; 95% CI, 0.646-2.360; P = 0.516). The frequency of severe pneumonitis in the poor PS group was significantly higher than that in the good PS group (25% vs. 2%, P = 0.010). Conclusion : Survival benefit of nivolumab in patients with NSCLC with poor PS, especially 3 or 4, was not confirmed. Further studies with larger numbers of patients are required to confirm our results., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Left atrial (LA) dilation is associated with morbidity of atrial fibrillation (AF). However, little is known about pulmonary vein (PV) dilation., Purpose: We investigated the PV volume in the patients with AF., Methods and Results: We performed 3dimensional computed tomography (3DCT) in 155 patients and divided them into three groups: 19 patients without AF (non-AF group, mean age 66 ± 12 years), 50 with paroxysmal AF (PAF group, mean age 67 ± 8 years) and 24 with persistent AF (PeAF group, mean age 64 ± 10 years). The absence of AF was diagnosed in patients with a cardiac implantable electronic device for at least 1 year (mean: 59 ± 37 months). We determined the PV volume as the total volume from the orifice to the first branch of each PV. According to the echocardiographic data, the LA dimension (LAD) and LA volume index (LAVI) were largest in the PeAF group followed by the PAF and non-AF group. According to the morphometric data obtained on 3D-CT, the PV volume was similar in PeAF and PAF groups but significantly smaller in the non-AF group (median value: 24 vs 21 vs 14 mL, respectively). According to the receiver operating characteristic curve analysis, the area under the curve for the PV volume in the presence of AF was 0.80, and the optimum cut-off value was 17 mL (sensitivity 74%, specificity 80%)., Conclusion: The PV volume might be useful for predicting the presence of AF before increases in the LAD and LAVI on echocardiography., Competing Interests: The authors declare no conflicts of interest for this article.