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To show surgical results of the intraoperative 3D fluorescein angiography-guided pars plana vitrectomy for branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.The NGENUITY 3D visualization system was used for the digital-assisted vitrectomy. Three-dimensional fluorescein angiography-guided pars plana vitrectomy was performed in three patients with branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.In all eyes, the scatter retinal photocoagulations for a nonperfusion area, depicted as hypofluorescein, and the segmentation and delamination of the perivascular fibrovascular proliferative membrane, depicted as hyperfluorescein, could be safely performed on the same screen while implementing intraoperative 3D fluorescein angiography.Three-dimensional fluorescein angiography-guided pars plana vitrectomy, a novel approach that fully uses the advantages of digital-assisted vitrectomy, can be one of the useful techniques for the treatment of branch retinal vein occlusion with vitreous hemorrhage and neovascularization elsewhere.

Background While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away. Methods We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among 11 Japanese private companies (n = 1209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis. Results During the 3.5-year period (follow-up rate: 99.9%), 1014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years. Conclusions Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

Background: Bronchial contraction and dilation is thought to be caused by non-adrenergic non-cholinergic nerves. Objective: To investigate the effects of low-frequency (1-5 Hz) and highfrequency (50-100 Hz) electric acupuncture (EA) stimulation on bronchial dilation. Design: Prospective, single-center study Setting: Teikyo Heisei University Subjects: Seventeen healthy male adults Randomization: We randomly assigned subjects to 2-Hz EA and 100-Hz EA groups in a crossover trial. The washout period was 2 weeks. Intervention: Both groups underwent a respiratory function test, followed by a 5-minute rest, followed a 5-minute rest or EA stimulation, followed by a 5min rest. Heart rate variability was measured at rest, followed by another respiratory function test. Acupuncture was delivered near the cervical ganglia at the level of the sixth cervical vertebra on the left side. EA stimuli were set to 2-Hz or 100-Hz, and stimulation intensity was set to a level where no pain was felt. Main outcome measures: Spirometry (forced vital capacity, forced expiratory volume in 1 s, and maximum respiratory flow), autonomic nerve activity (low-frequency component, high-frequency component, and their ratio), and heart rate variability. Results: Heart rate variability analysis showed significant differences in heart rate between the 2-Hz EA and 100-Hz EA groups. The 2-Hz EA group showed a significant increase in HF.Conclusions: 2-Hz EA stimulation resulted in decreased heart rate and increased HF during stimulation. This may be more effective for regulation of the autonomic nerves of the cardiopulmonary system than 100-Hz EA stimulation. Future studies are required to confirm our findings.

The increasing incidence and mortality of young-onset colorectal cancer has drawn increasing attention. However, screening for young adults is controversial given the limited evidence regarding its effectiveness.We aimed to clarify the characteristics of young-onset colorectal cancer and to compare long-term outcomes of screening-detected colorectal cancer and non-screening-detected colorectal cancer.This was a retrospective cohort study.This study evaluated data from a colorectal cancer registry and medical records at a tertiary Japanese cancer center.All patients with colorectal cancer who were registered at a Japanese tertiary cancer center between January 2007 and December 2016 were included.The colorectal cancer cases were categorized as screening-detected colorectal cancer and non-screening-detected colorectal cancer, and patients were categorized into 3 age groups:50 years (young-onset), 50 to 75 years, and75 years. The baseline characteristics and survival outcomes of the groups were compared using Cox regression models.A total of 4345 patients were identified, with a median follow-up of 4.6 years. Relative to 50- to 75-year-old individuals, young-onset colorectal cancer was linked to a higher proportion of rectal cancer (50.4% vs 43.3%), a lower proportion of screening-detected colorectal cancer (29.4% vs 35.8%), a lower proportion of stage I colorectal cancer (15.2% vs 30.3%), and a higher proportion of stage III to IV colorectal cancer (64.0% vs 49.4%). Among patients who were50 years old, screening-detected colorectal cancer was associated with a 50% lower risk of mortality relative to non-screening-detected colorectal cancer (HR, 0.50; 95% CI, 0.26-0.95).The findings were limited by the retrospective analysis from a single center.Young-onset colorectal cancer was more likely to present at an advanced stage and had a lower rate of screening-detected colorectal cancer. Nevertheless, young-onset screening-detected colorectal cancer was associated with better overall survival than non-screening-detected colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B829 .ANTECEDENTES:La creciente incidencia y mortalidad del cáncer colorrectal en paciente joven ha atraído una atención cada vez mayor. Sin embargo, el cribado para adultos jóvenes es controvertido, dado la evidencia limitada con respecto a su efectividad.OBJETIVO:Nuestro objetivo fue identificar las características del cáncer colorrectal en paciente joven y comparar los resultados a largo plazo del cáncer colorrectal detectado por cribado y el cáncer colorrectal no detectado por cribado.DISEÑO:Este fue un estudio de cohorte retrospectivo.ESCENARIO:Este estudio evaluó datos de un registro de cáncer colorrectal y registros médicos en un centro oncológico terciario japonés.PACIENTES:Se incluyeron todos los pacientes con cáncer colorrectal registrados en un centro oncológico terciario japonés entre enero de 2007 y diciembre de 2016.PRINCIPALES MEDIDAS DE RESULTADO:Los casos de cáncer colorrectal se categorizaron como cáncer colorrectal detectado mediante cribado y cáncer colorrectal no detectado mediante cribado, y los pacientes se clasificaron en tres grupos de edad:50 años (joven), 50-75 años y75 años. Las características basales y los resultados de supervivencia de los grupos se compararon mediante modelos de regresión de Cox.RESULTADOS:Se identificaron un total de 4345 pacientes, con una mediana de seguimiento de 4,6 años. En relación con las personas de 50 a 75 años, el cáncer colorrectal de inicio en la juventud se relacionó con una mayor proporción de cáncer de recto (50,4% frente a 43,3%), una menor proporción de cáncer colorrectal detectado mediante exámenes de cribado (29,4% frente a 35,8%), una menor proporción de cáncer colorrectal en estadio I (15,2% frente a 30,3%) y una mayor proporción de cáncer colorrectal en estadio III-IV (64,0% frente a 49,4%). Entre los pacientes menores de 50 años, el cáncer colorrectal detectado mediante cribado se asoció con un 50% menos de riesgo de mortalidad, en comparación con el cáncer colorrectal no detectado mediante cribado (HR: 0,50; IC 95%: 0,26-0,95).LIMITACIONES:Los hallazgos fueron limitados por el análisis retrospectivo de un solo centro.CONCLUSIONES:El cáncer colorrectal en paciente joven presenta más probabilidades de presentarse en una etapa avanzada y con una tasa más baja de detección mediante cribado. No obstante, el cáncer colorrectal detectado por cribado de aparición temprana se asoció con una mejor supervivencia general que el cáncer colorrectal no detectado por cribado. Consulte Video Resumen en http://links.lww.com/DCR/B829 . (Traducción-Dr. Felipe Bellolio ).

Background/Aims:Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn’s disease (CD)., Methods:Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing., Results:The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids., Conclusions:Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients.

BACKGROUND Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence due to mental disorders. METHODS Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on long-term sickness absence (LTSA) was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into

PURPOSE To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC)-injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial failure (CEF). DESIGN Comparative, interventional case series. METHODS This study involved 18 eyes with CEF that underwent cultured hCEC-injection therapy, categorized into two groups: 1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs [Group 1 (Gr1)], and 2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs [Group 2 (Gr2)]. From 1-week to 3-years postoperative, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's 'spring constant' was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers. RESULTS At 3-years postoperative, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3,083 cells/mm2; range, 2,182-4,417 cells/mm2) was higher than that in Gr1 (1,349 cells/mm2; range, 746-2,104 cells/mm2) (P < 0.001), and the spring constant verified the superiority of the mature cultured hCECs. From 24-weeks through 3-years postoperative, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < 0.005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed. CONCLUSION Our findings showed that mature cell SPs for hCEC-injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years post surgery.

Background Pain in knee osteoarthritis is considered to be nociceptive. Recently, involvement of neuropathic pain and psychosocial factors in knee osteoarthritis has been reported. However, the following details are unclear: 1) How often are neuropathic pain and psychosocial factors involved? And 2) Which patients are associated with neuropathic pain and psychosocial factors? Methods In 104 patients with knee osteoarthritis, we evaluated neuropathic pain factor with a painDETECT questionnaire and catastrophic thinking using the pain catastrophizing scale. Pain intensity was assessed using the visual analog scale; patients with scores below the median were defined as low-pain group and others as high-pain group. Radiographic severity was categorized according to the Kellgren–Lawrence classification, with grades I–II and III–IV defined as low- and high-grades, respectively. We compared the painDETECT and pain catastrophizing scale scores between the low- and high-pain groups and low- and high-grade groups. Furthermore, the painDETECT and pain catastrophizing scale scores were compared among the following four groups: low-grade/low-pain, low-grade/high-pain, high-grade/low-pain, and high-grade/high-pain. Results Neuropathic pain factor and catastrophic thinking were found in 16% and 34% of patients, respectively. There were no significant differences in both painDETECT and pain catastrophizing scale scores between the two pain intensity groups. Between the two groups of radiographic severity, there was no significant difference in the painDETECT scores; however, the pain catastrophizing scale score was significantly high in the low-grade group. In addition, there was no significant difference in the painDETECT scores among the four groups; however, the pain catastrophizing scale scores were significantly higher in low-grade/high-pain than in high-grade/low-pain patients. Conclusions Therefore, 64% had only nociceptive pain factor. Catastrophic thinking was strong in patients with low radiographic severity, especially in those with high pain intensity. Patients with neuropathic pain factor could not be identified from radiographic severity and pain intensity.

BackgroundPalliative sedation is sometimes needed for refractory symptoms, and the Richmond Agitation-Sedation Scale (RASS) is one of the key measures. The primary aim of this study was to explore the association between the RASS score and degree of distress quantified by other measures: Support Team Assessment Schedule, item 2 (STAS), Discomfort Scale for Dementia of Alzheimer Type (Discomfort Scale), and Non-communicative Patient’s Pain Assessment Instrument (NOPPAIN), as well as a communication capacity measured by the Communication Capacity Scale, item 4 (CCS).MethodsThis was a prospective observational study on terminally ill cancer patients who received continuous infusion of midazolam to relieve refractory symptoms in a palliative care unit of a designated cancer hospital. Primarily responsible palliative care physicians rated RASS, Discomfort Scale, NOPPAIN, and CCS just before starting infusion, and 1 hour, 4 hours, 24 hours, and 48 hours after midazolam infusion, and ward nurses rated STAS at the same time. Since the ward nurses regularly evaluated STAS to titrate midazolam during palliative sedation as routine work, we regarded STAS rated by ward nurses as a standard of distress measure.ResultsA total of 249 assessments were performed for 55 patients. The RASS score was moderately to highly associated with symptom intensity measured by STAS, discomfort measured by the Discomfort Scale, and pain measured by NOPPAIN (r = 0.63 to 0.73). On the other hand, communication capacity measured by CCS is not parallel with the RASS score, and demonstrated a valley-shape. In 82 assessments with RASS of -1 to -3, 11 patients (13%) were regarded as having physical symptoms of STAS of 2 or more.Conclusions RASS can roughly estimate physical distress in patients receiving palliative sedation, but a measure to more precisely quantify the symptom experience is needed.

Introduction: Treatment for patients with comorbid lymphedema and varicose veins is controversial. Surgical options for these patients are limited. The study was aimed to investigate the validity o...

Cervical esophageal adenocarcinoma has a low incidence rate and its treatment involves various strategies. We report a patient with locally advanced cervical to upper esophageal adenocarcinoma who was able to undergo induction chemotherapy and radical surgery. A 55-year-old man was diagnosed with a poorly differentiated adenocarcinoma between the cervical and upper thoracic esophagus. The primary lesion had infiltrated into the tracheal membrane and had metastasized into the cervical lymph nodes. The initial diagnosis was T4bN1M1 stage IVB. The lower edge of the tumor was close to the tracheal bifurcation, making it difficult to create a longitudinal tracheal foramen during surgery. Therefore, when biweekly-DCF therapy was performed as induction chemotherapy, the tumor shrank sufficiently and its infiltration into the tracheal membrane decreased subsequently. We performed total laryngopharyngoesophagectomy with three-field lymph node dissection and reconstruction using free jejunal grafts and subtotal stomach via a posterior mediastinum route and a permanent tracheal foramen as a radical surgery. The pathological diagnosis was T2/MP, N1, and the effect of chemotherapy was grade 2. Cervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

Purpose: The goal of this study is to clarify the underlying mechanisms of metastasis suppression by CiDC (carbon-ion radiotherapy (CIRT) combined with immature dendritic cell (iDC) immunotherapy), which was previously shown to significantly suppress pulmonary metastasis in a NR-S1-bearing C3H/He mouse model. Methods and Materials: Mouse carcinoma cell lines (LLC, LM8, Colon-26 and Colon-26MGS) were grafted into the right hind paw of syngeneic mice (C57BL/6J, C3H/He and BALB/c). Seven days later, the tumors on the mice were locally irradiated with carbon-ions (290 MeV/n, 6 cm SOBP, 1 or 2 Gy). At 1.5 days after irradiation, bone marrow-derived immature dendritic cells were administrated intravenously into a subset of the mice. The number of lung metastases was evaluated within three weeks after irradiation. In vitro cultured cancer cells were irradiated with carbon-ion (290 MeV/n, mono-energy, LET approximately 70 ∼ 80 keV/µm), and then co-cultured with iDCs for three days to determine the DC maturation. Results: CiDC effectively repressed distant lung metastases in cancer cell (LLC and LM8)-bearing C57BL/6J and C3H/He mouse models. However, Colon-26 and Colon-26MGS-bearing BALB/c models did not show enhancement of metastasis suppression by combination treatment. This was further evaluated by comparing LM8-bearing C3H/He and LLC-bearing C57BL/6J models with a Colon-26-bearing BALB/c model. In vitro co-culture assays demonstrated that all irradiated cell lines were able to activate C3H/He or C57BL/6J-derived iDCs into mature DCs, but not BALB/c-derived iDCs. Conclusion: The genetic background of the host may have a strong impact on the potency of combination therapy. Future animal and clinical testing should evaluate host genetic factors when evaluating treatment efficacy.

Aims Musculoskeletal toxicity is a typical side effect of daptomycin (DAP). However, the risk factors have not been well established. Here, we aimed to identify independent factors affecting DAP-induced musculoskeletal toxicity using a combination of machine learning and conventional statistical methods. Methods A population-based, retrospective, observational cohort study was conducted using the Japanese electronic medical record database. Patients who received DAP between October 2011 and December 2020 were enrolled. Two definitions of musculoskeletal toxicity were employed: (1) elevation of creatine phosphokinase (CPK) value more than twice from baseline and >200 IU/L, and (2) >1000 IU/L. First, multiple logistic regression analyses (a conventional statistical method) were performed to identify independent factors affecting CPK elevation. Then, decision tree analyses, a machine learning method, were performed to detect combinations of factors that change CPK elevation risk. Results Of the 2970 patients who received DAP, 706 were included. Elevation of CPK values >200 IU/L and >1000 IU/L occurred in 83 (11.8%) and 17 (2.41%) patients, respectively. In multiple logistic regression analysis, baseline CPK value and concomitant use of hydrophobic statins were commonly extracted as independent factors affecting each CPK elevation, but concomitant use of hydrophilic statins was not. In decision tree analysis, patients who received hydrophobic statins and had high baseline CPK values were classified into the high-risk group. Conclusion Our novel approach revealed new risk factors for CPK elevation. Our findings suggest that high-risk patients require frequent CPK monitoring.

Purpose Some clinical studies have reported the occurrence of nausea and vomiting with linezolid (LZD) administration. However, no studies have evaluated nausea and vomiting as primary endpoints. In a previous study, we noted a possible relationship between LZD and vomiting, but risk factors were not identified. Therefore, the aim of the present study was to identify them. Methods Patients who received LZD 600 mg twice daily at Hokkaido University Hospital from September 2008 to April 2019 were enrolled in this retrospective observational study. Patient characteristics, concomitant medications, laboratory data, and the occurrence of vomiting were obtained from electronic medical records. Logistic regression analysis was performed to identify risk factors for vomiting, including age, sex, body weight, concomitant medications, and surgeries. Results A total of 496 patients were included in this study, of which 90 experienced vomiting. By multivariate logistic regression analysis, female sex (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.62-4.47), >= 10 days of LZD administration (aOR, 2.57; CI, 1.46-4.50), and hyponatraemia (aOR, 2.96; CI, 1.72-5.10) were identified as independent risk factors for vomiting; administration of serotonergic agents (aOR, 0.23; CI, 0.07-0.82) was negatively associated. Conclusions This study is the first to successfully identify risk factors for LZD-induced vomiting. Careful monitoring of patients with these risk factors may lead to safer and sustainable LZD administration.

Aims/Introduction To investigate the national trend in the prescription of first‐line non‐insulin antidiabetic agents and total medical costs (TMCs) after prescribing the drug in Japanese patients with type 2 diabetes. Materials and Methods Using the National Database of Health Insurance Claims and Specific Health Check‐ups of Japan covering almost the entire Japanese population, we calculated the proportion of each antidiabetic drug from 2014 to 2017, and determined the factors associated with drug selection. The TMCs in the first year after starting the drugs were calculated, and factors associated with the costs were also determined. Results Among 1,136,723 new users of antidiabetic agents, dipeptidyl peptidase‐4 inhibitors were the most prescribed (65.1%), followed by biguanides (15.9%) and sodium–glucose cotransporter 2 inhibitors (7.6%). Sodium–glucose cotransporter 2 inhibitor and biguanide use increased during 2014–2017 (2.2%–11.4% and 13.7%–17.2%, respectively), whereas the others decreased. Biguanides were not prescribed at all in 38.2% of non‐Japan Diabetes Society‐certified facilities. The TMCs were the lowest among those who started with biguanides. Fiscal year, age, sex, facility, number of beds and comorbidities were associated with drug choice and TMCs. There were wide regional variations in the drug choice, but not in the TMCs. Conclusions Unlike in the USA and Europe, dipeptidyl peptidase‐4 inhibitor is the most prescribed first‐line medication for type 2 diabetes patients in Japan, while there is a wide variation in the drug choice by facility‐type and prefecture.

Objective Early enteral nutrition is essential for enhancing recovery after surgery. However, to date, no detailed study has been conducted on the feasibility of early enteral nutrition in patients undergoing head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) and the risk factors for difficulty with early enteral nutrition. Methods We retrospectively analyzed 102 patients who underwent HNS-FTTR at our institution; 61 underwent free jejunal reconstruction (FJ) and 41 did not. We investigated the achievement of early enteral nutrition within 24 and 48 h after surgery and the discontinuation of enteral nutrition after its initiation within 7 days after surgery. Results Enteral nutrition could be started in 81/102 (79.4%) and 99/102 (97.1%) patients within 24 and 48 h, respectively. Cases of difficulty with early enteral nutrition accounted for 21/102 (20.6%) patients. The multivariate analysis revealed that FJ was a significant independent risk factor for difficulty with early enteral nutrition (odds ratio: 4.054, P = 0.042). The risk factors for difficulty with early enteral nutrition in patients who underwent FJ were also investigated, and the multivariate analysis showed that blood loss of ≥158 mL was a significant independent risk factor (odds ratio: 3.505, P = 0.044). Conclusions Early enteral nutrition seemed to be provided with no problems in patients without FJ. FJ was a significant risk factor for difficulty with early enteral nutrition. Increased intraoperative blood loss was a significant risk factor for difficulty with early enteral nutrition in patients undergoing FJ; therefore, patients’ abdominal symptoms and gastric residual volume should be carefully monitored in such cases.

Introduction The purpose of this study was to evaluate the clinical applicability of urinary creatinine clearance (CrCl) for determining the initial dose of vancomycin (VCM) in critically ill patients and to assess VCM trough plasma concentration/maintenance daily dose (C/D) ratio in patients with augmented renal clearance (ARC). Methods As the primary outcome measure, correlations between estimated renal function and the VCM C/D ratio were compared using the following formulas: CrCl, Cockcroft-Gault equation (eCrClC-G) and KineticGFR equation (KeGFR). Patients were divided into those with or without changes in renal function. The patients were further classified based on the presence or absence of ARC. The secondary outcome was the comparison of VCM C/D ratio between ARC and Non-ARC patients. Results A total of 65 patients were enrolled for analysis. In all groups, CrCl tended to correlate better with the VCM C/D ratio than eCrClC-G and KeGFR. A significantly lower VCM C/D ratio was observed in patients with persistent ARC than in the Non-ARC group (0.24 versus 0.52 kg/L). Conclusions The clinical applicability of CrCl for the initial dosing design of VCM in critically ill patients was shown. Furthermore, the results indicated that patients with persistent ARC required a higher VCM dose than Non-ARC patients. Although our findings are limited, they have a value for further verification.

Background: Acute changes in glomerular filtration rate (GFR) can occur following initiation of interventions for chronic kidney disease (CKD) progression. These complicate the interpretation of treatment effects on long term progression of (CKD). We sought to assess the magnitude and consistency of acute effects in randomized clinical trials (RCT) and explore factors that might impact them. Methods: We performed a meta-analysis of 53 RCTs for CKD progression enrolling 56,413 participants that had at least one estimated GFR measurement by six months following randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable meta-regression to assess the impact of intervention type, disease state, baseline GFR and albuminuria on the magnitude of acute effects. Results: The mean acute effect across all studies was -0.21 mL/min/1.73m2 (95% CI -0.63 to 0.22) over three months, with substantial heterogeneity across interventions (95% coverage interval across studies, -2.50 to +2.08 mL/min/1.73m2). Negative average acute effects were observed in renin angiotensin system blockade, blood pressure lowering and sodium-glucose cotransporter 2 inhibitor trials while positive acute effects were observed in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with higher mean baseline GFR. Conclusion: The magnitude and consistency of acute GFR effects varies across different interventions, and is larger at higher baseline GFR. Understanding the nature and magnitude of the acute effects can help inform the optimal design of RCTs in CKD evaluating kidney disease progression.

We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC).A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients75 and ≥75 years old were compared.The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651).The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.

Background Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous neuromuscular disorder characterized by muscle weakness and caused by mutations in more than 35 different genes. This condition should not be overlooked as a subset of patients with CMS are treatable. However, the diagnosis of CMS is often difficult due to the broad variability in disease severity and course. Case report A five-year-old boy without remarkable family history was born with marked general muscle hypotonia and weakness, respiratory insufficiency, anomalies, and multiple joint contractures. Congenital myopathy was suspected based upon type 1 fiber predominance on muscle biopsy. However, he was diagnosed with CMS at age 4 years when his ptosis and ophthalmoplegia were found to be improved by edrophonium chloride and repetitive nerve stimulation showed attenuation of compound muscle action potentials. An exome sequencing identified a compound heterozygous missense variant of c.737C > T (p.A246V) and a novel intronic insertion c.1166 + 4_1166 + 5insAAGCCCACCAC in RAPSN. RT-PCR analysis which showed the skipping of exon 7 in a skeletal muscle sample confirmed that the intronic insertion was pathogenic. His myasthenic symptoms were remarkably improved by pyridostigmine. Conclusion The patient’s diagnosis of CMS was confirmed by exome sequencing, and RT-PCR revealed that the skipping of exon 7 in RAPSN was caused by a novel intronic insertion. The genetic information uncovered in this case should therefore be added to the collection of tools for diagnosing and treating CMS.

Introduction Autosomal dominant mitochondrial DNA depletion syndrome (MTDPS-12A) is characterized by severe hypotonia from birth due to a mutation in the adenine nucleotide translocator 1 (ANT1). Case report A 4-year-old female patient diagnosed with neonatal-onset mitochondrial disease, who had good cognitive function while receiving antiepileptic treatment, presented with sudden-onset status epilepticus with facial and limb myoclonus persisting for more than 30 min. Subsequently, she developed epileptic encephalopathy. Brain MRI showed progressive ventricular enlargement and marked white matter atrophy. She was unable to perform verbal communication or make eye contact and fingertip movements. She lacked any signs of cardiomyopathy. Sanger sequencing demonstrated a heterozygous de novo mutation of c.239G>A (p.Arg80His) in SLC25A4. Her right quadriceps muscle tissue showed lowered complexes I, III, and IV activities and mitochondria DNA depletion (mitochondria/nuclear DNA: 14.6 ± 2.2%) through the quantitative polymerase chain reaction. She was definitively diagnosed with MTDPS-12A. Conclusion Status epilepticus causes encephalopathy in patients with MTDPS-12A. Reducing the energy requirement on the cardiac muscle and brain may be a treatment strategy for patients with MTDPS-12A. Therefore, seizure management and preventive treatment of status epilepticus are considered to be important for maintaining neurodevelopmental outcomes.

Background The albumin‐bilirubin (ALBI) grade was developed to predict the prognosis of patients with hepatocellular carcinoma (HCC), which can stratify the prognosis even in HCC patients with Child‐Pugh A. We evaluated the prognostic efficacy of the ALBI grade and Child‐Pugh classification in HCC patients with Child‐Pugh A stratified by the presence or absence of advanced fibrosis or a preoperative biomarker for advanced fibrosis. Methods We retrospectively analyzed 490 consecutive HCC patients with Child‐Pugh A who underwent initial hepatectomies. The accuracy of prognostic prediction using both models was compared by the presence or absence of advanced fibrosis (F3‐4) and its predictor, the preoperative platelet count (PLT). Results The prognostic accuracy of the ALBI grade was better in patients without advanced fibrosis (F3‐4; likelihood ratio: 4.39, corrected Akaike information criterion [AICc]: 453.0, P = .074), but Child‐Pugh score was better in the advanced fibrosis group (likelihood ratio: 10.67, AICc: 915.2, P = .0014). In the high PLT group (≥140 × 103/μL), the prognostic accuracy using the ALBI grade was better in overall survival (OS) and relapse‐free survival (RFS), but in the low PLT group, the Child‐Pugh score was the more accurate model in OS and RFS. Conclusions Depending on the degree of fibrosis or preoperative PLT, the ALBI grade and Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A., Depending on the degree of fibrosis and preoperative platelet count (PLT), the albumin‐bilirubin (ALBI) grade or Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A.

Introduction Retropubic parasymphyseal cysta are rare, and few cases have been reported in men. Case presentation A 65‐year‐old male patient presented with a 6‐month history of pelvic and perineal pain. Magnetic resonance imaging revealed a high‐intensity, irregular‐shaped mass extending from the pubic symphysis to the bladder. Contrast enhancement revealed no uptake in the central part of the mass, indicating a cystic component. Computed tomography showed erosion of the pubic symphysis and pubic osteophytes. Pathological findings of biopsy specimens revealed inflammatory fibrous tissue but no malignancy. The definitive diagnosis was retropubic parasymphyseal cyst associated with inflammation. The patient was treated with cefazolin from 1 day before surgery until postsurgical day 7. Oral antibiotic therapy was then prescribed for 1 month to maximize treatment. After 2 months, the patient’s symptoms resolved. Conclusion Retropubic parasymphyseal cysts with inflammation and smaller asymptomatic cysts can be managed effectively with conservative or minimally invasive treatment.

We report a successful case that offered a symbolic therapeutic experience of interventional radiology and surgery collaboration for superior mesenteric artery thrombosis. A 70-year-old man presented with a chief complaint of sudden abdominal pain. Contrast-enhanced computed tomography revealed superior mesenteric artery thrombosis. Interventional radiology was performed, and thrombotic occlusion was observed in the superior mesenteric artery trunk. The abdominal pain disappeared; however, after a while, the thrombus re-formed and the abdominal pain reappeared. Thus, emergency surgery was performed. Before surgery, thrombus aspiration was performed via interventional radiology as much as possible. During surgery, when the blood flow was evaluated using fluorescence with indocyanine green, a region of markedly poor blood flow was detected in the ileum, and the area was excised. The postoperative course was favorable. In this patient, it is possible that preoperative removal of the thrombus via interventional radiology minimized the ischemic area of the intestinal tract, and blood flow evaluation using indocyanine green allowed reliable excision of only the ischemic area. We believe that our case involved a treatment that exploited the advantages of both interventional radiology and surgery using indocyanine green fluorescence.

Background/aim At present, there are no biomarkers to predict the effects of molecular targeted drugs in patients with CRC with liver metastasis. Thus, we performed this study to explore potential biomarkers for these patients. Materials and methods We obtained cancer tissue specimens from liver metastasis-bearing CRC patients who received the following preoperative neoadjuvant chemotherapies with molecular targeted drugs: i) no therapy (n=3), ii) 5-FU+oxaliplatin+anti-EGFR (n=3), iii) and 5-FU+oxaliplatin+anti-VEGF (n=3). Results We investigated the RNA expression of 84 genes related to cancer drug resistance using an RT-PCR array. The MYC gene was the only gene that was significantly up-regulated in CRC tissue specimens from anti-EGFR group in comparison to the anti-VEGF group. Conclusion MYC up-regulation in the primary CRC tissues may be a potentially useful biomarker for selecting anti-EGFR combination therapy in neoadjuvant chemotherapy for CRC with liver metastasis.

Background and Aims Cold-snare endoscopic mucosal resection (CS-EMR) has been adapted in a piecemeal fashion as a safe and effective procedure for resection of colorectal polyps ≥10 mm. However, few data are available on en bloc CS-EMR for adenomas of 10 to 14 mm. Thus, this study evaluated the efficacy and safety of CS-EMR for these colorectal adenomas. Methods In this single-arm, prospective, observational study, patients with at least 1 slightly elevated and sessile colorectal adenoma measuring 10 to 14 mm were recruited to undergo CS-EMR. The primary outcome was histological complete resection rate by CS-EMR, which was defined as en bloc resection, with a pathologically negative vertical margin and no neoplastic tissue obtained from 4 quadrants of the mucosal defect margin. Secondary outcomes were en bloc resection rate by CS-EMR, failure rate of CS-EMR, and the incidence of adverse events. Results A total of 80 polyps from 72 patients were included. CS-EMR failed in 11 lesions (13.7%), all of which were resected using a high-frequency electric current. The rates of en bloc resection and histologic complete resection by CS-EMR were 82.5% (66 of 80) and 63.8% (51 of 80), respectively. No bleeding occurred during the CS-EMR procedure, and there was no delayed bleeding or perforation at the site where CS-EMR was performed. Conclusions CS-EMR can be safely performed in an en bloc fashion for some colorectal adenomas measuring 10 to 14 mm. However, there is room for improvement regarding the resectability and evaluation of the vertical margin after CS-EMR. (Clinical trial registration number: UMIN000031248.)

A 75-year-old woman was diagnosed with anemia during hospitalization for the treatment of right superior ophthalmic arteriovenous fistula. Colonoscopy revealed an entire circumference of type 2 tumor in the ascending colon. Computed tomography showed ascending colon wall thickening, a tumor with a maximum diameter of 32 mm on the right external iliac artery and multiple low-density nodules in the spleen. We performed right hemicolectomy with D3 lymph node dissection, splenectomy and right external iliac lymph node dissection. Histopathological finding revealed moderately-differentiated adenocarcinoma in ascending colon and right external iliac lymph node. The lesion of spleen was diagnosed as splenic lymphangioma. The patient was discharged on postoperative day 18. Additional treatments, including chemotherapy, were not performed, and no recurrences were seen up to 66 months after surgery. We herein report an uncommon event of ascending colon cancer with synchronous right external iliac lymph node metastasis, which was successfully treated by surgical resection, made feasible when the distant lymph node metastasis is localized.

Background: Takotsubo syndrome (TTS) in the very elderly is poorly understood. We sought to clarify the characteristics of octogenarians and nonagenarians with TTS. Methods and Results: From 148 patients with TTS who underwent coronary angiography, 68 very elderly patients aged ≥80 years (octogenarians/nonagenarians) were compared with 80 younger patients aged ≤79 years. Emotional triggers of TTS were less frequent (7% vs. 19%; P=0.043), whereas physical triggers were more frequent (69% vs. 46%; P=0.005), in octogenarians/nonagenarians than in patients aged ≤79 years. As initial clues to the diagnosis, electrocardiogram changes were more frequent (71% vs. 46%; P=0.003) and chest pain and/or dyspnea were less common (25% vs. 51%; P=0.001) in octogenarians/nonagenarians than in patients aged ≤79 years. Twenty-nine patients had acute heart failure (AHF) as a complication. AHF was more frequently found in octogenarians/nonagenarians than in patients aged ≤79 years (29% vs. 11%, respectively; P=0.006). Cardiac death occurred in 2 octogenarians/nonagenarians; non-cardiac death occurred in 3 octogenarians/nonagenarians and in 2 patients aged ≤79 years. Conclusions: Emotional triggers of TTS were infrequent in octogenarians/nonagenarians with TTS. AHF was common and there was significant in-hospital all-cause mortality among octogenarians/nonagenarians.

Background/aim Although systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple. Material/methods From September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6=68:27, TNM stage II:III=17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST). Results Atez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR) and disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/42.5% and 84.7%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%). Conclusion Atez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition. This article is protected by copyright. All rights reserved.

BACKGOUND Cold snare polypectomy (CSP) can minimize the risk of adverse events and has become a standard treatment for small colorectal polyps. CSP might also be suitable for small superficial non-ampullary duodenal epithelial tumors (SNADETs). This study aimed to evaluate the safety of CSP for SNADETs. METHODS The major indication criteria were as follows: (1) endoscopically diagnosed SNADET, (2) ≤ 10 mm, and (3) a single primary lesion. CSP was performed using an electrosurgical snare without electrocautery. Follow-up endoscopy and scar biopsy were performed 3 months after CSP. The primary endpoint was the delayed adverse events rate. RESULTS In total, 21 patients were enrolled. Two and 19 lesions were located in the duodenal bulb and 2nd portion, respectively; the median lesion size was 8 mm. CSP was attempted for all lesions; three lesions could not be resected without electrocautery and were removed by conventional endoscopic mucosal resection (EMR). The rate of spurting bleeding after CSP was 0%. The median procedure time was 12 min, the median resected specimen size was 12 mm, and the rate of en bloc resection was 81% (17/21). No adverse events were observed intraoperatively, with no delayed adverse events after CSP. Histopathology revealed 15 adenomas, 4 cancers (intramucosal), and 2 non-neoplastic lesions. The horizontal margins were negative/positive/undetermined in 9, 1, and 11 cases, respectively. All vertical margins were negative. Only one recurrence was detected by follow-up endoscopy 3 months after CSP. CONCLUSIONS CSP can be performed safely for small SNADETs. CLINICAL TRIAL REGISTRATION This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm ), and the registration number is UMIN000019157.

Summary: Background & Aims: The prevalence of artificially administered nutrition and hydration (AANH) in different age groups among patients with advanced cancer remains unknown. The present study investigated the current utilization of AANH according to age groups in palliative care units. Methods: This was a secondary analysis of a prospective cohort study. We obtained information on primary nutritional administration routes during the first week of admission and data on the averaged calorie sufficiency rate or total calorie intake on the 7th day of admission. Patients were divided into five age groups (18–39, 40–59, 60–74, 75–89, and 90- years). Among patients receiving AANH, the proportions of higher-calorie AANH were compared between the five age groups. Results: A total of 1453 patients were included. The proportion of patients categorized as receiving nutrition and hydration via the parenteral route was the highest in the 18–39 and 40–59 groups (52.4 and 41.1%, respectively). Among patients receiving AANH (n = 534), the proportions of patients categorized into the

Purpose: It has been reported that 5.1-7.0% of acute pericarditis is carcinomatous pericarditis. Malignant pericardial effusion (MPE) can progress to cardiac tamponade, which is a life-threatening condition. The effectiveness and feasibility of intrapericardial instillation of carboplatin (CBDCA; 150 mg/body) have never been evaluated in patients with lung cancer, which is the most common cause of MPE. Therefore, we evaluated the effectiveness and feasibility of intrapericardial administration of CBDCA following catheter drainage in patients with lung cancer-associated MPE.Methods: In this retrospective study, 21 patients with symptomatic lung cancer-associated MPE, who were administered intrapericardial CBDCA (150 mg/body) at Gunma Prefectural Cancer Center between January 2005 and March 2018, were included. The patients’ characteristics, response to treatment, and toxicity incidence were evaluated.Results: Thirty days after the intrapericardial administration of CBDCA, MPE was controlled in 66.7% of the cases. The median survival period from the day of administration until death or last follow-up was 71 days (range: 10–2435 days). Grade 1–2 pain, nausea, fever, and neutropenia were noted after intrapericardial CBDCA administration. No treatment-related deaths were noted in current study.Conclusions: Intrapericardial administration of CBDCA (150 mg/body) did not cause serious toxicity, and patients exhibited promising responses to lung cancer-associated MPE. Prospective studies using larger sample sizes are needed to explore the efficacy and safety of this treatment for managing lung cancer-associated MPE.

The science operations of the spacecraft and remote sensing instruments for the Martian Moon eXploration (MMX) mission are discussed by the mission operation working team. In this paper, we describe the Phobos observations during the first 1.5 years of the spacecraft’s stay around Mars, and the Deimos observations before leaving the Martian system. In the Phobos observation, the spacecraft will be placed in low-altitude quasi-satellite orbits on the equatorial plane of Phobos and will make high-resolution topographic and spectroscopic observations of the Phobos surface from five different altitudes orbits. The spacecraft will also attempt to observe polar regions of Phobos from a three-dimensional quasi-satellite orbit moving out of the equatorial plane of Phobos. From these observations, we will constrain the origin of Phobos and Deimos and select places for landing site candidates for sample collection. For the Deimos observations, the spacecraft will be injected into two resonant orbits and will perform many flybys to observe the surface of Deimos over as large an area as possible. Graphical Abstract

BACKGROUND End-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PURPOSE To clarify the clinical implications of ADPAF in adults. METHODS AND RESULTS The study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSE

Objectives To investigate the prevalence and risk factors of labor-onset hypertension (LOH), defined as hypertension first detected during labor among women without hypertension prior to admission for labor. Study design In this multicenter retrospective study, clinical data of women who delivered vaginally at term between 2012 and 2018 were collected from 12 primary maternity care units. Blood pressure was measured at five time points from admission to 2 h postpartum in a total of 30,129 normotensive women at the last prenatal check-up. LOH was defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg during the first to fourth stages of labor. Main outcome measures Multivariate regression analyses were conducted to evaluate the risk factors of LOH and severe LOH (SBP of ≥ 160 mmHg or DBP of ≥ 110 mmHg). Results Among the 30,129 women, 8,565 (28.4%) presented with LOH and 734 (2.4%) with severe LOH. The prevalence of LOH was the highest at the second stage of labor (21.7%) and decreased rapidly after delivery. The independent risk factors of LOH were maternal age of ≥ 35 years, pre-pregnancy body mass index of ≥ 25 kg/m2, and pregnancy weight gain of ≥ 15 kg. Conclusion LOH is common, with approximately one in four women experiencing LOH during labor and early postpartum. Meanwhile, severe LOH occurred in 2.4% of the pregnancies. Closer blood pressure monitoring during labor may enable obstetric caregivers to recognize LOH in a timely manner and reduce maternal adverse outcomes, such as eclampsia and stroke.

Objective: In patients with liver cirrhosis, the clinical characteristics of dynapenia, a condition in which skeletal muscle mass is maintained but muscle strength is reduced, are not yet known. This study aimed to clarify the characteristics of dynapenia and its impact on quality of life (QOL) in patients with liver cirrhosis. Methods: We retrospectively analyzed 116 patients with cirrhosis. Based on grip strength and skeletal muscle mass measured by the bioelectrical impedance analysis method, patients were divided into four groups: normal muscle status, dynapenia, pre-sarcopenia (a condition involving only low muscle mass), and sarcopenia. The characteristics of dynapenia and its influence on QOL were examined. Results: Fourteen patients had dynapenia. Liver function did not differ among the four groups. In patients with dynapenia, BMI was highest and computed tomography attenuation of skeletal muscle at the third lumbar spine vertebra was lowest among the four groups. The percentage of patients with both BMI ≥25 kg/m2 and myosteatosis was significantly higher in patients with dynapenia [9/14 (64.3%)] than in those with sarcopenia [2/23 (8.7%), P = 0.004] and pre-sarcopenia [0/18 (0%), P < 0.001] and tended to be higher than those with normal muscle status [16/61 (26.2%), P = 0.065]. The physical QOL in patients with dynapenia was as low as that in those with sarcopenia and significantly lower than that in those with normal muscle status. Conclusion: Cirrhotic patients with dynapenia had high BMI and myosteatosis, and impaired physical QOL.

Purpose:Thermal rheology (TR) fluid, which comprises polyethylene (PE) particles, their dispersant, and solvent, is a material that increases in viscosity to various degrees depending on the type and ratio of these constituents when its temperature rises. The viscosity of type 1 (TRF-1) increases more than that of type 2 (TRF-2) near rabbit body temperature. This preliminary animal study aimed to determine the basic characteristics and embolic effect of TR fluid by comparing TRF-1 and TRF-2., Materials and methods:Twenty-four Japanese white rabbits underwent unilateral renal artery embolization using TRF-1 or TRF-2 and follow-up angiography at 7 or 28 days (4 subgroups, n = 6 each). Subsequently, the rabbits were euthanized, and the embolized kidneys were removed for pathological examination. The primary and final embolization rates were defined as the ratio of renal artery area not visible immediately after embolization and follow-up angiography, respectively, to visualized renal artery area before embolization. The final embolization rate and maximum vessel diameter filled with PE particles were compared between materials. Moreover, the embolic effect was determined to be persistent when a two-sided 95% confidence interval (CI) for the difference in means between the embolization rates was < 5%., Results:The final embolization rate was significantly higher for the TRF-1 than for the TRF-2 at both 7 (mean 80.7% [SD 18.7] vs. 28.4% [19.9], p = 0.001) and 28 days (94.0% [3.5] vs. 37.8% [15.5], p < 0.001). The maximum occluded vessel diameter was significantly larger for TRF-1 than for TRF-2 (870 µm [417] vs. 270 µm [163], p < 0.001). The embolic effect of TRF-1 was persistent until 28 days (difference between rates - 3.3 [95% CI - 10.0-3.4])., Conclusion:The embolic effect of TRF-1 was more persistent than that of TRF-2, and the persistency depended on the type and ratio of TR fluid constituents.

Background/objectives The diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been fully studied; however, the efficacy of other endoscopic samplings (OESs) is less clear. The aim of this study was to examine the diagnostic efficacies of OESs for pancreatic head cancer (PHC). Methods The diagnostic efficacies of endoscopic samplings were retrospectively analyzed in 448 PHC cases and 63 cases of mass-forming pancreatitis (MFP) during initial transpapillary biliary drainage. The OESs included duodenal biopsy (118 PHCs and 50 MFPs), biliary biopsy (218 and 51) with cytology (368 and 53), and pancreatic duct biopsy (23 and 13) with cytology (56 and 43). EUS-FNA was conducted in a different session (149 and 62). Factors associated with OES sensitivity were analyzed. The sensitivity of biliary biopsy was compared between 1.95 mm and 1.8 mm forceps. Results Cancer cells were confirmed in 87.9% of the EUS-FNA samplings and in 64.1% (268/418) obtained by combined OESs (average 1.7 OES types per case): 68.6% by duodenal biopsy, 59.6% by biliary biopsy, 32.6% by biliary cytology, 73.9% by pancreatic duct biopsy, and 33.9% by pancreatic duct cytology. No MFP cases revealed cancer by any sampling. OESs did not increase adverse events. Duodenal stenosis, serum bilirubin, tumor size, and pancreatic juice amounts were associated with OES sensitivity. Biliary biopsy had the same sensitivity with different forceps. Conclusion EUS-FNA was the most diagnostic protocol; however, OESs can be safely applied during the initial biliary drainage to reduce the demand for EUS-FNA while providing good diagnostic yields.

Background/Aim: With the development of systemic treatment methods for unresectable hepatocellular carcinoma (uHCC), the concept of unsuitable for transcatheter arterial chemoembolization (TACE) has become important. This study aimed to establish a simple predictive scoring system for determining TACE unsuitable status. Materials/Methods: From 1998 to 2015, 196 patients with intermediate-stage uHCC with Child-Pugh A (score 5:6 = 108:88) and given TACE as the initial treatment were enrolled. At the baseline, tumor burden (Milan criteria-out, up-to-7 in/out, and up-to-11 in/out: 0–2 points) and modified albumin-bilirubin grade 1/2a or 2b (0–1 point) were added to determine the score for TACE unsuitable (CITRUS-MICAN score; low Results: Median survival time (MST) was better for low compared to high CITRUS-MICAN score (42.0 vs. 26.4 months) (p = 0.002). A 2-step evaluation using the combination of CITRUS-MICAN and TM scores showed an MST of 43.2 months for low CITRUS-MICAN/TM score 0/1 (rank-A) and 39.6 months for low CITRUS-MICAN/TM score ≥2 (rank-B2), while it was 46.8 months for high CITRUS-MICAN/TM score 0 (rank-B1), 28.8 months for high CITRUS-MICAN/TM score 1 (rank-B2), and 22.8 months for high CITRUS-MICAN/TM score ≥2 (rank-C). For rank-A cases (n = 51), MST was 43.2 months, while it was 46.8 months for rank-B1 (n = 12), 31.2 months for rank-B2 (n = 82), and 22.8 months for rank-C (n = 51) (p = 0.001). Conclusion: The results showed that rank-C indicates absolute TACE unsuitable status. For rank-A patients, good prognosis with TACE can be expected, while TACE refractoriness status during the clinical course should be carefully evaluated so as to anticipate the appropriate timing for switching to systemic treatment in rank-B1 and -B2 patients.

Paediatric high-risk neuroblastoma has poor prognosis despite modern multimodality therapy. This phase I/II study aimed to determine the safety, dose-limiting toxicity (DLT), and efficacy of high-dose 131I-meta-iodobenzylguanidine (131I-mIBG) therapy combined with single high-dose chemotherapy (HDC) and haematopoietic stem cell transplantation (HSCT) in high-risk neuroblastoma in Japan. Patients received 666 MBq/kg of 131I-mIBG and single HDC and HSCT from autologous or allogeneic stem cell sources. The primary endpoint was DLT defined as adverse events associated with 131I-mIBG treatment posing a significant obstacle to subsequent HDC. The secondary endpoints were adverse events/reactions, haematopoietic stem cell engraftment and responses according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and 123I-mIBG scintigraphy. Response was evaluated after engraftment. We enrolled eight patients with high-risk neuroblastoma (six females; six newly diagnosed and two relapsed high-risk neuroblastoma; median age, 4 years; range, 1–10 years). Although all patients had adverse events/reactions after high-dose 131I-mIBG therapy, we found no DLT. Adverse events and reactions were observed in 100% and 25% patients during single HDC and 100% and 12.5% patients during HSCT, respectively. No Grade 4 complications except myelosuppression occurred during single HDC and HSCT. The response rate according to RECIST 1.1 was observed in 87.5% (7/8) in stable disease and 12.5% (1/8) were not evaluated. Scintigraphic response occurred in 62.5% (5/8) and 37.5% (3/8) patients in complete response and stable disease, respectively. 131I-mIBG therapy with 666 MBq/kg followed by single HDC and autologous or allogeneic SCT is safe and efficacious in patients with high-risk neuroblastoma and has no DLT. jRCTs041180030. Feasibility of high-dose iodine-131-meta-iodobenzylguanidine therapy for high-risk neuroblastoma preceding myeloablative chemotherapy and haematopoietic stem cell transplantation (High-dose iodine-131-meta-iodobenzylguanidine therapy for high-risk neuroblastoma). https://jrct.niph.go.jp/en-latest-detail/jRCTs041180030 . 12/01/2018.

BACKGROUND After hepatitis C virus (HCV) elimination, patients should be followed up due to risk of hepatocellular carcinoma (HCC). Growth differentiation factor 15 (GDF15) is a cytokine induced by mitochondrial dysfunction or oxidative stress. Aim To evaluate the prognostic value of GDF15 for HCC occurrence after HCV elimination. METHODS We measured GDF15 levels in stored serum from patients with chronic HCV infection without a history of HCC who had achieved sustained virological response with direct-acting antiviral agents (DAAs). The patients were randomly divided into derivation (n = 964) and validation (n = 642) cohorts. RESULTS In the derivation cohort, serum GDF15 levels were higher in those with HCC occurrence after DAA treatment than in those without. Multivariate Cox proportional hazards analysis revealed baseline GDF15 (>1350 pg/mL, HR 2.54), AFP (>5 ng/mL, HR 2.00), and the FIB-4 index (>3.25, HR 2.69) to be independent risk factors for HCC. Scoring based on GDF15, AFP and the FIB-4 index stratified HCC occurrence risk. In the validation cohort, the cumulative HCC occurrence rate at 3 years was 0.64%, 3.27% and 15.3% in low-score (N = 171), medium-score (N = 300) and high-score (N = 166) groups, respectively. In the total cohort, scoring divided patients with a FIB-4 index ≤3.25, whose HCC occurrence rate was 2.0% at 3 years, into medium-score and low-score groups with HCC occurrence rates at 3 years of 3.76% and 0.24%, respectively. CONCLUSIONS Serum GDF15 predicts de novo HCC occurrence. Scoring using GDF15, AFP, and the FIB-4 index can predict de novo HCC occurrence risk after HCV elimination.

Although the incidence of the various gynecological cancers has been increasing in recent years, long-term survival is now possible for many patients thanks to advances in multimodality treatment. When treating gynecological cancer in adolescent and young adult (AYA) patients who desire future pregnancy, it is necessary to preserve the reproductive organs and their function to prevent loss of fertility. However, because treatment targets these organs, in the large majority of cases, patients must have these organs removed. In the subfield of oncofertility, treatment of the underlying disease takes priority, and the main principle is preventing delay in treatment. Close cooperation between obstetricians and gynecologists involved in reproductive medicine and oncologists involved in cancer treatment is necessary. In addition, it is important that clinicians work closely not only with other specialists but also with such medical professionals as nurses and counselors so that cancer patients of the AYA generation can be provided the support they need to fight their cancer with hope. Herein, we describe the current status of fertility-sparing therapy for AYA patients with gynecological cancer (cervical cancer, endometrial cancer, or ovarian cancer). In addition, we explain points to keep in mind during a patient's pregnancy after fertility preservation, the latest findings on assisted reproductive technology, and the challenges and prospects of fertility preservation therapy for patients with gynecologic cancer.

Placing a transanal endoscopic rectal purse-string suture (taEPS) is the crucial first component of transanal total mesorectal excision (taTME). However, no structured training is available to improve the procedure-specific skills for taEPS. The aim of this study was to create a performance rubric to improve taEPS skills and provide preliminary evidence for its validity. A performance rubric was created based on technical considerations for taEPS, identified by consulting with taTME surgical and performance assessment experts. Ten independent, blinded raters assessed 10 videotaped taEPS procedures of consecutive taTME cases, at National Cancer Center Hospital East (NCCHE), Chiba, Japan, in January 2018–March 2019 using the rubric and the Global Operative Assessment of Laparoscopic Skills (GOALS). Internal consistency and inter-rater reliabilities were calculated. Videotaped taEPS procedures were timed and assessed by the rubric. Correlation between rubric scores and suturing times were analyzed. The rubric consists of four items: loading the needle (LN), atraumatic needle passage (AP), planned suture path (PS), and overall performance (OA). Videotaped performances were graded on a 3-point Likert scale; scores were calculated as sums of the points. Cronbach’s α for internal consistency was 0.713. Inter-rater reliabilities were LN: 0.73, AP: 0.76, PS: 0.71, and OA: 0.70. Rubric and GOALS scores were strongly correlated (r = 0.964, p

The global population is aging, and elderly people have a higher incidence of lower airway diseases owing to decline in swallowing function, airway ciliary motility, and overall immunity associated with aging. Furthermore, lower airway diseases in the elderly tend to have a high mortality rate. Their prevention is important for extending healthy life expectancy and improving the quality of life of each individual. In recent years, the relationship between "chronic periodontitis and oral bacteria, especially the periodontopathic ones" and "respiratory diseases" (e.g., pneumonia, chronic obstructive pulmonary disease, and influenza) has become clear. In addition, the association of several periodontal pathogens with the onset and aggravation of coronavirus disease 2019 (COVID-19) is also being reported. In support of these findings, oral health management has shown to reduce deaths from pneumonia and prevent influenza in nursing homes and inpatient wards. This has led to clinical and multidisciplinary cooperation between physicians and dentists, among others. However, to date, the mechanisms by which "chronic periodontitis and oral bacteria" contribute to lower airway diseases have not been well understood. Clarifying these mechanisms will lead to a theoretical basis for answering the question, "Why is oral health management effective in preventing lower airway diseases?"

Objective: No standard treatment for cancer-related fatigue (CRF) for inpatients in a palliative care setting exists. The aim of this study was to validate the previous study-derived efficacy of dexamethasone 8 mg for CRF among inpatients in a palliative care setting. Methods: Inpatients with moderate fatigue (≥4/10) were enrolled in a multicenter phase II trial. Dexamethasone 8 mg p.o. or 6.6 mg i.v. was administered for seven days and 4 mg p.o. or 3.3 mg i.v. for seven consecutive days. The primary endpoint was a threshold average change of Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue subscale score of 3. The secondary endpoints were evaluated with the anorexia-cachexia subscale (ACS), and the Edmonton symptom assessment scale-revised Japanese version. Results: A total of 32 patients were enrolled. On day 8, the mean change of FACIT-fatigue subscale from day 1 was 5.2 (95% confidence interval 0.8–10.0), in which the lower bound was above 0 but not above the prespecified threshold value of 3.0 (p = 0.72). Edmonton symptom assessment system (ESAS)-fatigue was significantly improved by day 3 (p = 0.02), but not on day 8 or day 15. ACS, physical well-being, and ESAS-lack of appetite significantly improved by day 8 and day 15. Adverse events were tolerable. Conclusion: This study showed that dexamethasone 8 mg failed to achieve the preset efficacy for CRF among inpatients in a palliative care setting. However, this treatment improved fatigue and would be an option for CRF. jRCT (jRCTs031180068).