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Abstract Background Sentinel lymph node biopsy (SLNB) underuse has been reported for skin cancers; however, actual performance rates have not been compared. The objective of this study was to investigate the SLNB performance rate in skin cancers covered by health insurance in Japan and compare it with that in breast cancer. Methods This was a retrospective study of the SLNB performance rate in SLNB‐eligible patients with breast or skin cancer from 2018 to 2019, utilizing a database linked to the Hospital‐Based Cancer Registry and Diagnosis Procedure Combination survey. Demographic and tumor characteristics were analyzed using logistic regression. Results A total of 71,652 patients were included in this study. SLNB was performed in 86.4% (57,904/67,036) of the patients with breast cancer, 44.7% (694/1552) with melanomas, 3.1% (89/2849) with squamous cell carcinomas (SCCs), and 13.5% (29/215) with Merkel cell carcinomas (MCCs). The performance rate of SLNB was significantly lower for skin cancers than for breast cancers (odds ratio [OR], 0.03; p

Abstract Background Intravenous (IV) fluid therapy is essential in the treatment of critically ill pediatric surgery and trauma patients. Recent studies have suggested that aggressive fluids may be detrimental to patients. Prospective studies are needed to compare liberal to restricted fluid management in these patients. The primary objective of this pilot trial is to test study feasibility—recruitment and adherence to the study treatment algorithm. Methods We conducted a two-part pilot randomized controlled trial (RCT) comparing liberal to restricted crystalloid fluid management in 50 pediatric post-operative (1–18 years) and trauma (1–15 years) patients admitted to our pediatric intensive care unit (PICU). Patients were randomized to a high (liberal) volume or low (restricted) volume algorithm using unblinded, blocked randomization. A revised treatment algorithm was used after the 29th patient for the second part of the RCT. The goal of the trial was to determine the feasibility of conducting an RCT at a single site for recruitment and retention. We also collected data on the safety of study interventions and clinical outcomes, including pulmonary, infectious, renal, post-operative, and length of stay outcomes. Results Fifty patients were randomized to either liberal (n = 26) or restricted (n = 24) fluid management strategy. After data was obtained on 29 patients, a first study analysis was performed. The volume of fluid administered and triggers for intervention were adapted to optimize the treatment effect and clarity of outcomes. Updated and refined fluid management algorithms were created. These were used for the second part of the RCT on patients 30–50. During this second study period, 54% (21/39, 95% CI 37–70%) of patients approached were enrolled in the study. Of the patients enrolled, 71% (15/21, 95% CI 48–89%) completed the study. This met our a priori recruitment and retention criteria for success. A data safety monitoring committee concluded that no adverse events were related to study interventions. Although the study was not powered to detect differences in outcomes, after the algorithm was revised, we observed a non-significant trend towards improved pulmonary outcomes in patients on the restricted arm, including decreased need for and time on oxygen support and decreased need for mechanical ventilation. Conclusion We demonstrated the feasibility and safety of conducting a single-site RCT comparing liberal to restricted crystalloid fluid management in critically ill pediatric post-operative and trauma patients. We observed trends in improved pulmonary outcomes in patients undergoing restricted fluid management. A definitive multicenter RCT comparing fluid management strategies in these patients is warranted. Trial registration ClinicalTrials.gov, NCT04201704 . Registered 17 December 2019—retrospectively registered.

Summary:. Recently, lymphatic ultrasonography has received increasing attention. Although there are several reports on contrast-enhanced lymphatic ultrasound as a preoperative examination for lymphaticovenous anastomosis (LVA), we have been reporting the usefulness of preoperative noncontrast lymphatic ultrasound. In this article, the detailed procedure for conducting lymphatic ultrasound during the preoperative examination of LVA is thoroughly described. The only items required for lymphatic ultrasound are an ultrasound device, an echo jelly, a straw for marking, and a marker. We use an ordinary ultrasound device with an 18-MHz linear probe. We apply the Doppler, Crossing, Uncollapsible, Parallel, and Superficial fascia index to identify the lymphatic vessels. While imagining the course of the lymph vessels, we position the probe perpendicular to the long axis of the lymphatic vessels. When a vessel is found under the superficial fascia, the probe is moved proximally to trace the vessel’s path. If the vessel transverses a nearby vein without connecting to it, it is most likely a lymphatic vessel. To confirm, we ensure that the vessel does not exhibit coloration in the Doppler mode. As LVA is most effective when the dilated lymph vessels are anastomosed, we use lymphatic ultrasound to identify the most dilated lymphatic vessels in each lymphosome, and mark incision lines where suitable veins are in close proximity. No contrast agent is required; therefore, medical staff such as nurses and ultrasound technicians can autonomously conduct the test.

Abstract Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation of Grem1 cells in mice. Transcriptomic and functional analysis in mice found that articular surface Grem1-lineage cells are dependent on Foxo1 and ablation of Foxo1 in Grem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting in Grem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition of Grem1 expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA.

Abstract Background The timing of cardiac surgery with cardiopulmonary bypass (CPB) for intracranial hemorrhage is controversial. Case presentation We report the case of an 82-year-old woman who was transferred to our hospital because of a head injury. Brain computed tomography (CT) revealed traumatic intracranial hemorrhage, and transthoracic echocardiography revealed a giant right atrial myxoma. After confirming the disappearance of intracranial hemorrhage on brain CT, cardiac surgery with CPB was performed, which was uneventful. Conclusions For an uneventful surgery, the optimal timing of cardiac surgery with CPB in patients with giant right atrial myxoma and intracranial hemorrhage should be based on brain CT.

Abstract More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

Abstract Background Early and accurate preoperative diagnosis of complicated appendicitis mandates the identification of new markers. The aim of this study is to determine whether preoperative serum sodium levels are useful for predicting the severity of acute appendicitis. Methods We retrospectively analyzed 475 patients who underwent emergency appendectomies between January 2018 and February 2023 in a general hospital in Brazil. The patients were divided into 2 groups: complicated (n = 254) and uncomplicated (n = 221). Hyponatremia was defined as serum sodium levels

Background: In children with asthma, there are many cases in which wheeze is confirmed by auscultation with a normal lung function, or in which the lung function is decreased without wheeze. Using an objective lung sound analysis, we examined the effect of wheeze and the lung function on lung sound parameters in children with asthma. Methods: A total of 114 children with asthma (males to females = 80: 34, median age 10 years old) were analyzed for their lung sound parameters using conventional methods, and wheeze and the lung function were checked. The effects of wheeze and the lung function on lung sound parameters were examined. Results: The patients with wheeze or decreased forced expiratory flow and volume in 1 s (FEV1) (% pred) showed a significantly higher sound power of respiration and expiration-to-inspiration sound power ratio (E/I) than those without wheeze and a normal FEV1 (% pred). There was no marked difference in the sound power of respiration or E/I between the patients without wheeze and a decreased FEV1 (% pred) and the patients with wheeze and a normal FEV1 (% pred). Conclusions: Our data suggest that bronchial constriction in the asthmatic children with wheeze similarly exists in the asthmatic children with a decreased lung function. A lung sound analysis is likely to enable an accurate understanding of airway conditions.

Elisabeth J Adams,1 Alexander van Doornewaard,1 Yixuan Ma,1 Nurilign Ahmed,1 Man Ki Cheng,1 Henrik Watz,2 Masakazu Ichinose,3 Tom Wilkinson,4 Mohit Bhutani,5 Christopher J Licskai,6– 8 Katy M E Turner1 1Aquarius Population Health, London, UK; 2Pulmonary Research Institute at Lungen Clinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 3Academic Center of Osaki Citizen Hospital, Osaki, Japan; 4Southampton University Faculty of Medicine, Southampton, UK; 5University of Alberta, Edmonton, Alberta, Canada; 6London Health Sciences Centre, Western University, London, Ontario, Canada; 7Lawson Health Research Institute, London, Ontario, Canada; 8Asthma Research Group Windsor Essex County Inc., Windsor, Ontario, CanadaCorrespondence: Elisabeth J Adams, Aquarius Population Health, Unit 29 Tileyard Studios, London, N7 9AH, UK, Tel +44 207 993 2930, Email Elisabeth.adams@aquariusph.comIntroduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations.Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings.Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31– 38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5– 10%) to an integrated disease management (IDM) programme that provides guideline adherent care.Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£ 2.89 million; -€ 6.58 million; -$40.08 million; -¥ 735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£ 38.15 million; € 35.58 million; ¥ 1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size.Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.Keywords: health intervention, exacerbations, re-admission, integrated care, economic evaluation

Itaru Miura,1 Sho Horikoshi,1,2 Mizue Ichinose,1,3 Yuhei Suzuki,1 Kenya Watanabe4 1Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan; 2Department of Neuropsychiatry, Horikoshi Psychosomatic Clinic, Fukushima, Japan; 3Department of Neuropsychiatry, Hoshigaoka Hospital, Koriyama, Japan; 4Department of Pharmacy, Fukushima Medical University Hospital, Fukushima, JapanCorrespondence: Itaru Miura, Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Tel +81-24-547-1331, Fax +81-24-548-6735, Email itaru@fmu.ac.jpAbstract: This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D2, 5-hydroxytryptamine (5-HT)2A, and 5-HT7 receptors and a partial agonistic effect on the 5-HT1A receptor with low affinities for muscarinic M1, histamine H1, and a1 adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT7 and 5-HT1A receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.Keywords: schizophrenia, lurasidone, serotonin-dopamine antagonist, antipsychotics

A 44-year-old man with chronic idiopathic pseudo-intestinal obstruction and lumbar disc herniation presented with orthostatic dizziness, black vomiting, and stools. He was suspected to have an ulcer caused by nonsteroidal anti-inflammatory drugs and treated conservatively but continued to have transfusion-dependent anemia. Trans-arterial contrast-enhanced computed tomography showed multiple microbleeds in the small intestine. We diffusely embolized 7 small intestine branches of the superior mesenteric artery using imipenem/cilastatin on 2 separate occasions. This stopped the bleeding, and the patient progressed well without ischemic complications and was discharged on the 25th postoperative day.Transcatheter arterial embolization with imipenem/cilastatin may be a viable treatment option for patients with multiple small bowel bleeds in a large area of the small intestine that are unresponsive to conservative treatment or endoscopic methods.

In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results.

Abstract The impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.