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Background In current intensive care treatment, there are patients with severe burns who cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. Methods This was a single-center, retrospective, observational study. Patients’ blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. Results Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. Conclusions In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Background Necrotizing fasciitis (NF) is a life-threatening and acute progressive soft tissue infection and needs early surgical intervention, that is, debridement or amputation. Surgical strategy or prognosis is influenced by the speed of progression and patients’ general condition, which can be calculated by the Charlson Comorbidity Index (CCI). The purpose of this study was to investigate the association between the CCI scores and prognosis of patients with NF of the upper/lower extremities. Methods In the retrospective cohort study, we analyzed patients with NF of the upper/lower extremities who were determined to undergo surgery by orthopedic surgeons at four tertiary hospitals between August 2003 and April 2016. We divided the patients into two groups, Group L (low CCI scores of 0–2) and Group H (high CCI scores of ≥3). The primary event of this study was defined as death or amputation. Mortality cases were included when amputation was informed with documented certification but patients died while waiting for surgery. We compared the patients’ background, laboratory data on admission, the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, and primary outcome between the two groups. Results Of the 56 patients, 28 patients were classified into Group L and the other 28 patients into Group H. The data in this study showed that patients in Group H had lower white blood cell counts and hemoglobin and higher creatinine than Group L, but there was no difference in LRINEC scores between the two groups. Streptococcus pyogenes was the most common infectious agent in Group L (54%) but not in Group H (11%). Poorer outcome was observed in Group H compared with Group L (4 mortality and 16 amputation vs. no mortality and 9 amputation, P = 0.007). Conclusions Laboratory data and causative microorganisms were different between high CCI and low CCI patients with NF. High CCI scores were associated with limb amputation or death caused by NF of the upper/lower extremities; whereas, low CCI scores were more likely associated with S. pyogenes monoinfection.

Heat stroke is a debilitating disease that is characterised by inflammation, coagulation and tissue abnormalities.[1][1] Patients who have experienced heat stroke can manifest complications even after their body temperature has returned to normal.[1][1] However, data on the characteristics of

Rationale and Objectives Appropriate image manipulation of angiographic image display systems during interventional radiology is performed by radiological technologists and/or nurses given instructions from radiologists. However, appropriate images might not be displayed because of communication errors. Therefore, we developed a manipulation system that uses an eye tracker. The study aimed to determine if an angiographic image display system can be manipulated as well by using an eye tracker as by using a mouse. Materials and Methods An angiographic image display system using an eye tracker to calculate the gaze position on the screen and state of fixation was developed. Fourteen radiological technologists participated in an observer study by manipulating 10 images for each of 5 typical cases frequently performed in angiography, such as renal tumor, cerebral aneurysm, liver tumor, uterine bleeding, and hypersplenism. We measured the time from the start to the end of manipulating a series of images required when using the eye tracker and the conventional mouse. In this study, the statistical processing was done using Excel and R and R studio. Results The average time required for all observers for completing all cases was significantly shorter when using the eye tracker than when using the mouse (10.4 ± 2.1 s and 16.9 ± 2.6 s, respectively; p Conclusion Radiologists were able to manipulate an angiographic image display system directly by using the newly developed eye tracker system without touching contact devices, such as a mouse or angiography console. Therefore, communication error could be avoided.

A 58-year-old man was diagnosed with stage IVB lung adenocarcinoma in the right upper lobe and underwent systemic chemotherapy. Seven months after the diagnosis, large left pleural and pericardial effusion was detected. The patient developed both chylothorax and chylopericardium following superior vena cava (SVC) obstruction with mediastinal lymphadenopathy caused by lung carcinoma. Since conservative treatment of the chyle leakage was ineffective, we administered radiotherapy to treat the SVC obstruction and mediastinal lymphadenopathy. After radiotherapy, the chylothorax and chylopericardium gradually resolved, and no further chyle leaks were identified on follow-up computed tomography. This case indicates that radiotherapy can be used to ameliorate lung cancer-related chylothorax and chylopericardium.

Primary dyslipidemias are inherited disorders in plasma lipoprotein metabolism that lead to serious cardiovascular and other complications. The Japanese Ministry of Health, Labor and Welfare (MHLW) covers medical expenses, under the Research Program on Rare and Intractable Diseases, for homozygous familial hypercholesterolemia (FH), familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis, lecithin:cholesterol acyltransferase deficiency, Tangier disease, and abetalipoproteinemia. Apolipoprotein A1 deficiency, heterozygous FH, and type III hyperlipoproteinemia are covered by the MHLW Pediatric Chronic Disease Program. Heterozygous FH and type III hyperlipoproteinemia are also important for their relatively common prevalence and, accordingly, high impact on Japanese public health by significant contribution to the overall prevalence of cardiovascular diseases. Therefore, a systemic survey of these diseases is mandatory to estimate their actual situation, such as prevalence, clinical manifestations, and prognoses among the Japanese population. The impact of these rare and intractable diseases on cardiovascular and other complications will likely be higher among Japanese people than other ethnicities because the general Japanese population has many cardioprotective aspects. The current study intends to conduct a multicenter registry of these diseases to assess their demographics and clinical features comprehensively. Methods and Analysis: The Prospective Registry Study of Primary Dyslipidemia is a registry-based prospective, observational, multicenter cohort study in Japan, enrolling patients who fulfill the Japanese clinical criteria of the primary dyslipidemias listed above, from 26 participating institutes from August 2015 to March 2023. A total of 1,000 patients will be enrolled in the study and followed for 10 years. Clinical parameters are collected, including physical and laboratory findings, genetic analysis, drugs, lifestyle management, and clinical events, especially cardiovascular events. The primary endpoint of this study is the new onset of cardiovascular disease and acute pancreatitis, and the secondary endpoint is death from any causes. Ethics and Dissemination: This study complies with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. The institutional review boards have approved this study protocol at all participating institutes. The final results are to be published at appropriate international conferences and in peer-reviewed journals.

A 56-year-old postmenopausal woman with out-of-hospital cardiac arrest caused by acute myocardial infraction was successfully resuscitated by intensive treatments and recovered without any neurological disability. She was diagnosed as having familial hypercholesterolemia (FH) based on a markedly elevated low-density lipoprotein cholesterol (LDL-C) level and family history of premature coronary artery disease. Genetic testing in her family members showed that a variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.2004C＞A, p.S668R), which had been previously reported as having uncertain significance, was associated with FH, indicating that the variant is a potential candidate for the FH phenotype. Next-generation sequencing analysis for the proband also showed that there was a heterozygous mutation of the ATP-binding cassette sub-family G member 5 (ABCG5) gene (c.1166G＞A, R389H), which has been reported to increase LDL-C level and the risk of cardiovascular disease. She was also diagnosed as having type 1 CD36 deficiency based on a lack of myocardial uptake of 123 I-labeled 15-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid in scintigraphy and the absence of CD36 antigen in both monocytes and platelets in flow cytometry. She had a homozygous mutation of the CD36 gene (c.1126-5_1127delTTTAGAT), which occurs in a canonical splice site (acceptor) and is predicted to disrupt or distort the normal gene product. To our knowledge, this is the first report of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction in the present case.

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient's chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.

A 50-year-old man developed a sterile cavernosal abscess followed by prominent features of necrotizing neutrophilic dermatosis. We conducted a literature review, which revealed that aseptic abscesses in the corpus cavernosum occur in association with neutrophilic dermatosis. Patients with this condition frequently receive unnecessary antibiotic treatment and surgical interventions. Although this condition responds to systemic corticosteroids, the functional prognosis of the penis is poor. Abscess formation may be the initial presentation of neutrophilic dermatoses, and underlying conditions may even be absent. Clinicians need to be aware of this condition to distinguish it from bacterial infection and initiate early disease-specific treatments.

In brain magnetic resonance imaging (MRI) examinations, rapidly acquired two-dimensional (2D) T1-weighted sagittal slices are typically used to confirm brainstem atrophy and the presence of signals in the posterior pituitary gland. Image segmentation is essential for the automatic evaluation of chronological changes in the brainstem and pituitary gland. Thus, the purpose of our study was to use deep learning to automatically segment internal organs (brainstem, corpus callosum, pituitary, cerebrum, and cerebellum) in midsagittal slices of 2D T1-weighted images. Deep learning for the automatic segmentation of seven regions in the images was accomplished using two different methods: patch-based segmentation and semantic segmentation. The networks used for patch-based segmentation were AlexNet, GoogLeNet, and ResNet50, whereas semantic segmentation was accomplished using SegNet, VGG16-weighted SegNet, and U-Net. The precision and Jaccard index were calculated, and the extraction accuracy of the six convolutional network (DCNN) systems was evaluated. The highest precision (0.974) was obtained with the VGG16-weighted SegNet, and the lowest precision (0.506) was obtained with ResNet50. Based on the data, calculation times, and Jaccard indices obtained in this study, segmentation on a 2D image may be considered a viable and effective approach. We found that the optimal automatic segmentation of organs (brainstem, corpus callosum, pituitary, cerebrum, and cerebellum) on brain sagittal T1-weighted images could be achieved using SegNet with VGG16.

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m(2) intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between November 9, 2015 and January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

Supported by the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (GNT1116371), and by foundation partner, Boehringer Ingelheim, and program partners, Roche and Galapagos. Rationale : The interstitial lung disease (ILD) multidisciplinary meetings (MDM), composed of pulmonologists, radiologists, and pathologists, is integral to the rendering of an accurate ILD diagnosis. However, there is significant heterogeneity in the conduct of ILD MDMs, and questions regarding their best practices remain unanswered. Objectives : To achieve consensus among ILD experts on essential components of an ILD MDM. Methods : Using a Delphi methodology, semi-structured interviews with ILD experts were used to identify key themes and features of ILD MDMs. These items informed two subsequent rounds of online questionnaires that were used to achieve consensus among a broader, international panel of ILD experts. Experts were asked to rate their level of agreement on a five-point Likert scale. An a priori threshold for consensus was set at a median score 4 or 5 with an interquartile range of 0. Results : We interviewed 15 ILD experts, and 102 ILD experts participated in the online questionnaires. Five items and two exploratory statements achieved consensus on being essential for an ILD MDM following two questionnaire rounds. There was consensus that the presence of at least one radiologist, a quiet setting with a visual projection system, a high-quality chest high-resolution computed tomography, and a standardized template summarizing collated patient data are essential components of an ILD MDM. Experts also agreed that it would be useful for ILD MDMs to undergo an annual benchmarking process and a validation process by fulfilling a minimum number of cases annually. Twenty-seven additional features were considered to be either highly desirable or desirable features based on the degree of consensus. Although our findings on desirable features are similar to the current literature, several of these remain controversial and warrant further research. The study also showed an agreement among participants on several future concepts to improve the ILD MDM, such as performing regular self-assessments and conducting research into shared practices to develop an international expert guideline statement on ILD MDMs. Conclusions : This Delphi study showed consensus among international ILD experts on essential and desirable features of an ILD MDM. Our data represent an important step toward potential collaborative research into future standardization of ILD MDMs. Postprint

Aims/Introduction An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel‐based specific regional analysis system for Alzheimer’s disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. Materials and Methods We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. Results A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z‐score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P, We evaluated the utility of the voxel‐based specific regional analysis system of Alzheimer's disease, an automated brain morphometry system that includes the hippocampus, for screening unrecognized cognitive dysfunction in elderly patients with diabetes. This is the first report to assess the association between hippocampal atrophy and cognitive dysfunction by an automated voxel‐based morphometry system in clinical diabetes practice. The results suggest that the voxel‐based specific regional analysis system of Alzheimer's disease can be useful for early identification of cognitive dysfunction in the elderly with diabetes.

Background. Patients with Parkinson’s disease (PD) receiving levodopa treatment often report motor complications including wearing-off (WO), dyskinesia, and morning akinesia. As motor complications are associated with a decrease in patients’ quality of life (QoL), it is important to identify their occurrence and commence immediate management. This study investigated whether differences in the perception of motor complications exist between patients and their physicians in routine clinical practice. Methods. After an Internet-based screening survey, questionnaires were distributed to physicians and their patients in Japan. The 9-item Wearing-Off Questionnaire (WOQ-9) was used to objectively assess the presence of WO; patients with WOQ-9 scores ≥2 were considered to have WO. McNemar’s test was used to compare physician assessment versus WOQ-9 scores, patient self-awareness versus physician assessment, and patient self-awareness versus WOQ-9, separately. Morning akinesia and dyskinesia were assessed by both physician assessment and patient self-awareness with McNemar’s test. QoL was assessed using the 8-item Parkinson’s Disease Questionnaire (PDQ-8) with the Wilcoxon rank-sum test. Results. A total of 235 patients with PD and their 92 physicians participated in this survey. A significant discordance was observed between the WOQ-9 and physician assessment of WO (67.2% vs 46.0%; p < 0.0001 ). Furthermore, patient self-awareness of WO was 35.3% ( p = 0.0004 , vs physician). Morning akinesia (patient, 58.7%; physician, 48.9%; p = 0.0032 ), dyskinesia (patient, 34.0%; physician, 23.4%; p = 0.0006 ), and bodily discomfort (patient, 25.0; physician, 0.0; p = 0.0102 ) of QoL were underrecognized by physicians. Conclusions. This study investigated differences in the perception of WO between patients with PD and their physicians in routine clinical practice and highlighted that patients have a low awareness of the symptoms of WO compared with physician assessments and WOQ-9. Conversely, morning akinesia, dyskinesia, and bodily discomfort were underrecognized by physicians.

Background We encountered a 12-year-old girl with Takayasu arteritis (TA) who developed acute heart failure at onset. There have been few reports of specific treatment for acute heart failure (AHF) in TA. We successfully treated her with intravenous methylprednisolone and tocilizumab. Case presentation The patient developed palpitations and shortness of breath 3 weeks before admission. Her symptoms exacerbated rapidly and she finally entered our hospital intensive care unit due to respiratory distress and tachycardia. Blood pressure values measured on the left arm and bilateral legs were paradoxically lower than values taken on the right arm. Chest X-ray revealed a severely enlarged heart. Contrast computed tomography showed an expanded aorta, aortic aneurysm, meandering, and irregular diameter of the aorta. The left ventricular ejection fraction (LVEF) was 20% on cardiac ultrasound. Laboratory examination suggested acute inflammation and positivity of HLA-B52. Her medical condition was finally diagnosed as TA with AHF. Along with inotropes and diuretics, methylprednisolone pulse therapy was administered for 3 days on the 2nd and 12th hospital day followed by oral prednisolone. Cardiac function was slightly improved. As intravenous cyclophosphamide therapy requires hydration and may exacerbate AHF, we started weekly subcutaneous tocilizumab treatment (162 mg/week) from the 20th hospital day. Inotropes were discontinued on the 51st hospital day and her LVEF had improved to 37.5% on the 63rd day when she was discharged. Conclusions Tocilizumab could be a significant treatment option for acute heart failure in juvenile TA.

Background Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for non-invasive imaging. Aims We aimed to elucidate whether serum caffeine is independently associated with adenosine-induced fractional flow reserve (FFR) overestimation and their concentration-response relationship. Methods FFR was measured using adenosine (FFRADN) and papaverine (FFRPAP) in 209 patients. FFRADN overestimation was defined as FFRADN - FFRPAP. The locally weighted scatterplot smoothing (LOWESS) approach was applied to evaluate the relationship between serum caffeine level and FFRADN overestimation. Multiple regression analysis was used to determine independent factors associated with FFRADN overestimation. Results Caffeine was ingested at l12 hours in 85 patients, at 12-24 hours in 35 patients, and at g24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (pl0.001). The LOWESS curve demonstrated that FFRADN overestimation started from just above the lower detection limit of serum caffeine and increased approximately 0.01 FFR unit per 1 mg/L increase in serum caffeine level with a linear relationship. The 90th percentile of serum caffeine levels for the ≤12-hour, the 12-24-hour, and the g24-hour groups corresponded to FFRADN overestimations by 0.06, 0.03, and 0.02, respectively. Conclusions Serum caffeine overestimates FFRADN values in a linear concentration-response manner. FFRADN overestimation occurs at much lower serum caffeine levels than those that were previously believed. Our results highlight that standardised caffeine control is required for reliable adenosine-induced FFR measurements.

The subsuperior segmental bronchi (B*) forms the subsuperior segment (S*) between the superior (S6) and basal segment (S7, S8, S9, S10) of the lung. However, the anatomical planes of S* remains undefined. The present study clarified the anatomical features of S*. We reviewed the anatomical patterns of pulmonary vessels and the left lung bronchus in 539 patients using three-dimensional computed tomography. We report the anatomic structure in S*. A total of 537 patients were analyzed. B* was observed in 129 (24.0%) patients. The intersegmental vein between S6 and S* was complete in all cases. The absence of intersegmental veins of S* was observed in 77 (14.3%) patients, reaching 59.7% of B* cases. Twenty-two (4.1%) cases of B* diverged from the trunk of the basal bronchus, and about half of the B* branched to the dorsolateral (n = 77, 14.3%) or dorsal (n = 2, 0.37%) direction. Our study revealed the branching patterns of B* and anatomical intersegmental veins of S*. Our results provide useful information regarding anatomical segmentectomy including or adjusting to the left S*.

BACKGROUND The quality of end-of-life (Q-EOL) care is influenced by various factors such as resources for palliative care (PC). We introduced a multi-professional expert team (MET) in 2014, which provides home-based care for children and adolescents with incurable cancer. This study investigated the impacts of the outreach activities by the MET on Q-EOL care of pediatric oncology patients. METHODS This observational study retrospectively examined 112 patients receiving end-of-life care between 1989 and 2018 at a pediatric cancer center in Japan. Some of the indicators of Q-EOL care before and after the introduction of the outreach activities by the MET were compared. The subjects were 92 in pre-MET and 20 in post-MET periods. RESULTS The median number of days for which the patients stayed at home during the final seven or 30 days were significantly prolonged in the post-MET period (0.0 vs 1.5 days, P = 0.020, 3.0 vs 12.0 days, P = 0.042). The change was more significant in hematologic malignancies than solid and central nervous system tumors. Patients receiving longer PC before their deaths could stay at home longer during the last 7 days. The ratio of patients receiving PC for more than 2 months was significantly increased in post-MET period (60.9 vs 90.0%, P = 0.014). More patients also greeted their deaths at home in the post-MET period (3.3 vs 25.0%, P < 0.001). CONCLUSIONS The activities of the MET transformed the end-of-life care of children and adolescents with incurable cancer. Earlier transitions to PC from curative treatment were associated with longer home-based care and more deaths at home.

Objectives Methotrexate (MTX) is used as an anchor drug in the treatment of rheumatoid arthritis (RA), although more than a half of the patients with RA require additional treatments. We designed a prospective study involving two medical centers in Japan to examine the association between the expression of MTX-related genes including a drug transporter ATP-binding cassette sub-family G member 2 (ABCG2) gene and the clinical response to MTX in MTX-naive patients with RA. Methods The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. Results Based on the clinical response at 12 weeks after the initiation of MTX, 24 patients were classified into good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of the baseline gene expression levels to predict the EULAR good response at week 12 showed a significant association with ABCG2 expression alone. Furthermore, the rate of baseline expression of ABCG2 mRNA above the cut-off value determined using a receiver operating characteristic curve was higher in good responders than in non-good responders (p = .012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median −76% vs. +41% from baseline, respectively; p = .011). The ABCG2 expression level did not correlate with DAS28 at baseline or week 12. Conclusions Our study revealed that good response to MTX is associated with a decrease in the expression of ABCG2 in patients with RA.

Background Circulating tumor DNA (ctDNA) is a biomarker with potential to reflect comprehensive genomic information and overcome intratumor heterogeneity. In contrast, carcinoembryonic antigen (CEA) is a conventional tumor marker for predicting recurrence, survival, and chemotherapeutic efficacy in patients with metastatic colorectal cancer (mCRC). However, the relationship between them remains unclear. Here, the relationship between plasma ctDNA and CEA levels was evaluated to clarify the advantages and disadvantages of their clinical use. Methods A total of 110 patients with mCRC underwent chemotherapy were enrolled. Amplicon‐based plasma genomic profiling of 14 genes that are commonly mutated in CRC by next‐generation sequencing was compared to the CEA level and tumor diameter using Spearman’s correlation coefficient. Results The overall concordance rate between the ctDNA and CEA levels was 75.5% (83/110). The correlation coefficient between the ctDNA and CEA levels was lower in the group of patients without liver and lymph node metastases (r = 0.18, p = 0.44) than in the group of patients with liver metastasis (r = 0.48, p, Tumor diameter and ctDNA and CEA levels highly correlated in metastatic colorectal cancer patients with liver metastases. Status of ctDNA and CEA may not be consistent in metastatic colorectal cancer (mCRC) patients without liver metastasis or with low tumor volume. Both results should be considered when deciding a treatment strategy for mCRC patients without liver metastases.

Background Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). Methods Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. Results HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0–4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5–19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09–0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16–0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P Conclusions A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.

Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

Objective The precision of maxillary repositioning using computer-aided design/computer-aided manufacturing (CAD/CAM)-generated wafers and a surgical navigation system for bimaxillary orthognathic surgery (BMOS) using segmental Le Fort I osteotomy was evaluated. Methods Six participants with jaw deformities who required BMOS incorporating segmental Le Fort I osteotomy were included. The preoperative simulation was performed using a three-dimensional skull model on the simulation software, and a wafer for maxillary repositioning was prepared by CAD/CAM. Using the CAD/CAM-generated wafer and intraoperative navigation system, the maxillary segments were repositioned to agree with virtual surgical planning. The ideal movements of the preoperative simulation were compared with the actual movements after the surgery, and the errors of the ideal movements with reference to the actual movements were evaluated three-dimensionally at seven evaluation points. Results The largest and smallest median errors calculated from the differences between the ideal and actual 3-D movements were, respectively, 0.65 mm at anterior nasal spine, 0.02 mm at posterior nasal spine. There is no significant difference was observed between ideal and actual movements in either 2-D and 3-D. Conclusion The clinical accuracy of maxillary repositioning with the CAD/CAM wafer and an intraoperative navigation system in segmental Le Fort I osteotomy was revealed in the present study.

Background There are long-standing controversies about the transplant indications for alcoholic liver disease (ALD), because of the recognition that ALD is fundamentally self-inflicted. However, it is unclear whether psychosocial characteristics of ALD are different from that of non-alcoholic liver disease (NALD) in the selection of liver transplantation (LT) recipients. We aimed to clarify the psychosocial characteristics of ALD recipients (ALD-R)/ALD recipient candidates (ALD-RC) and NALD recipients (NALD-R)/ NALD recipient candidates (NALD-RC). Methods From 2011 to 2019, 75 patients were enrolled in this prospective observational study (ALD-RC, n = 19; NALD-RC, n = 56), LT were carried out as follow; ALD-R, n = 6; NALD-R, n = 52. We evaluated psychosocial characteristics in the preoperative period and 3, 12 months after LT (ALD-R, n = 3/3; NALD-R, n = 28/25). The following scales were used to evaluate psychosocial characteristics: Visual Analogue Scale, Alcohol Use Disorders Identification Test, Hospital Anxiety and Depression Scale, Beck Depression Inventory, Brief Evaluation of Medication Influences and Beliefs, Social Support Questionnaire (SSQ), Temperament and Character Inventory, Parental Bonding Instrument (PBI), the Short Form Health Survey (SF-36). Results When evaluating on the basis of abstinence rule, a comparison of ALD-RC and NALD-RC in the preoperative period identified similar patterns of psychosocial characteristics, except that the NALD-RC scored higher on the PBI item “overprotection from mother” (P Conclusion The psychosocial characteristics of ALD-RC and NALD-RC may be similar when evaluated on the basis of Japan’s abstinence rule. This result also imply that the psychosocial characteristics of ALD-RC may differ from the previously reported psychosocial characteristics of alcohol dependent patients. These findings have the potential to provide helpful information for the evaluation of ALD-RC.

Decompression surgery is the most common surgical treatment for lumbar spinal stenosis (LSS). Relatively low satisfaction rate was reported. Patients often complaint of residual numbness despite significant pain relief. We hypothesized that numbness had a significant impact on patient satisfaction, but had not been evaluated, which is associated with low satisfaction rate. This study aimed to examine how much numbness is associated with patient satisfaction. We retrospectively reviewed prospectively collected data from consecutive patients who underwent decompression without fusion for LSS. We evaluated the Numeric Rating Scale (NRS) scores of low back pain (LBP), leg pain, and leg numbness preoperatively and at the final follow-up visit. Improvement was evaluated using minimum clinically important differences (MCIDs). Patient satisfaction was evaluated using the question, "How satisfied are you with the overall result of your back operation?". There are four possible answers consisting of "very satisfied (4-point)", "somewhat satisfied (3-point)", "somewhat dissatisfied (2-point)", or "very dissatisfied (1-point)". Spearman correlation was used to evaluate the association between patient satisfaction and reaching MCIDs. A total of 116 patients were included. All three components had correlation with patient satisfaction with the correlation efficient of 0.30 in LBP, 0.22 in leg pain, and 0.33 in numbness. Numbness had greatest correlation efficient value. We showed that numbness has a greater impact than leg/back pain on patient satisfaction in patients undergoing decompression for LSS. We suggest not only LBP and leg pain but also numbness should be evaluated pre- and postoperatively.

Background Interstitial pneumonia (IP) is associated with high comorbidity of lung cancer (LC). We aimed to investigate whether concomitant IP affects palliative pharmacotherapy for end-stage symptom relief in patients with LC. Methods We retrospectively examined the clinical records of LC patients who died in our hospital between 2015 and 2017. The patients were divided into the IP-LC (LC with comorbid IP) and LC (LC without IP) groups according to the presence of IP to compare the use of opioid and midazolam in their terminal period. Results In total, 236 patients were enrolled in this study and divided into the IP-LC (n = 70) and LC (n = 166) groups. Among them, 51.2% and 65.7% patients in the LC and IP-LC groups, respectively, required continuous opioid administration to relieve dyspnea and/or pain. There were no significant between-group differences in the median initial and maximum doses and continuous opioid administration duration. The frequency of concomitant use of continuous midazolam and opioids was higher in the IP-LC group than in the LC group (20.5% vs. 7.1%; p = 0.01), primarily because of refractory dyspnea in all patients in both groups. The median survival time after the initiation of continuous opioid administration did not change irrespective of continuous midazolam administration. Conclusions Compared with patients with LC, those with IP-LC are more likely to require continuous midazolam administration because continuously administered opioids alone are not sufficiently effective in relieving end-stage dyspnea among the latter.

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues.

Oral administration of a water-soluble iodine contrast agent (gastrografin) was reported to assist in the appropriate contouring of the small intestine on computed tomography (CT)-based radiotherapy (RT) planning. The efficacy and optimal dose of gastrografin in CT-based image-guided brachytherapy (IGBT) for cervical cancer remain unknown. This study aimed to investigate the efficacy of pretreatment oral administration of gastrografin at a small dose of 50 ml in CT-based IGBT for cervical cancer. A total of 422 sessions in 137 patients who underwent CT-based IGBT with 50 ml of oral gastrografin (concentration, 3% or 4%) were analyzed. Preparation of gastrografin was judged as effective when the small intestine was contrast-enhanced at the area where the small intestine was in contact with the uterus/adnexa. About 287 out of 422 sessions (68%) were judged as effective with gastrografin preparation. The 135 ineffective sessions were considered as follows: (i) the contrast enhancement of the small intestine was not confirmed (n = 36), (ii) the small intestine was not in contact with the uterus/adnexa despite the confirmation of the contrast enhancement of the small intestine (n = 34), and (iii) gastrografin was absent in the small intestine at the area in contact with the uterus/adnexa, even when gastrografin was observed in the small intestine at the area not in contact with the uterus/adnexa (n = 65). In conclusion, pretreatment oral administration of a small dose gastrografin achieved moderate efficacy for accurate contouring of the small intestine close to the uterus/adnexa in CT-based IGBT for cervical cancer.

Aim To perform a systematic review of available mHealth apps for menstrual cycle monitoring in Brazil. Methods A search for menstrual cycle mHealth apps from the Google Play Store and AppStore in Brazil was performed by two independent reviewers on October 2020, and the quality of eligible mHealth apps was assessed using the Mobile App Rating Scale (MARS). Results Our review identified 2400 potentially relevant mHealth apps, of which 56 were eligible for inclusion. The majority of the apps offered tools to track menstruation symptoms (63%) and educational content for users (32%). The mean ( ±SD) MARS app quality score for the 28 evaluated apps in Android was 3.5 ± 0.6 on a 0-5 scale. For the 28 evaluated apps in iOS, the mean app quality score was 3.8 ± 0.4. Most of the included apps, for both systems, scored average for credibility, user interface, and engagement. Conclusion The majority of available tools in Brazil are of moderate quality and limited functionality for menstrual cycle monitoring. This study highlights the top three mHealth apps available on each online store for individuals seeking menstrual cycle monitoring options.

OBJECTIVES Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

Transcatheter aortic valve implantation (TAVI) is an alternative treatment to surgical aortic valve replacement for treating severe aortic stenosis. With the increased use of TAVI, the risk of cerebrovascular complications during the procedure has become an emerging problem. We evaluated the safety and feasibility of our total cerebral protection methods using embolic protection devices (EPDs) for carotid artery stenting. We collected the results of cases in which the clinical team determined that our protection method was necessary among patients undergoing TAVI from May to October 2019 in our medical center. We applied this method to patients who had a potentially high risk of cerebrovascular events during the procedure. The methods of protection were selected comprehensively based on the potential of collateralization of brain perfusion when some arteries were blocked with a balloon, accessibility of the brain arteries, and the ability to cover the brain arteries with devices. Five patients, aged 83.8 ± 1.8 years, were included in the study. Technical success was achieved in all five patients. No cases showed any new neurological symptoms after the procedures; however, head MRI on the day after showed new ischemic lesions in three of five cases (60%). In all cases, emboli were found in the collected filters. This report demonstrates protection of the entire perfusion area in each case using EPDs in patients at high risk of intraoperative embolism. The methods we used were feasible and can potentially reduce cerebrovascular events following TAVI.

Introduction: The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia. Methods: Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events. Results: Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, p = 0.0165; 27%, p = 0.0213, respectively). Four patients had a subsequent stroke within 7 days. Conclusion: Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology.

The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59–208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.

Background and study aims We sometimes encounter colorectal cancer (CRC) that is discovered during the time interval between initial colonoscopy and the recommended follow-up examination. Although several studies reported such cases of CRC, most were based on registry data, which implied that the endoscopic quality was not consistent or guaranteed. We aimed to clarify these clinical and endoscopic characteristics at our high-volume center where a retrospective survey could be precisely performed. Patients and methods We retrospectively analyzed patients with CRC who underwent endoscopic resection or surgery from April 2002 to December 2010, categorizing them into two groups: a “study group” of patients with a negative colonoscopy during the previous 10 years, and a “control group” of patients without a previous colonoscopy or with a previous colonoscopy more than 10 years prior. Results A total of 2042 patients had CRC, among which 55 patients were classified into the study group and the remaining 1989 into the control group. The CRC cases in the study group showed a significant association with smaller ( Conclusions Tumor size and location were associated with CRCs detected within 10 years after the negative examination. In addition, depressed-type T1 CRCs were more common. Therefore, we should pay more attention to small, right-sided, or depressed-type tumors in daily colonoscopy.

Recently, endoscopic ultrasound (EUS)-guided biliary drainage has been developed as an alternative biliary drainage technique for failed endoscopic retrograde cholangiopancreatography (ERCP) or inaccessible papilla. Among the various EUS-guided biliary drainage procedures, EUS-guided hepaticogastrostomy (HGS) can be performed in patients with surgically altered anatomy. More recently, various transluminal treatments have been described after EUS-HGS, such as antegrade stone removal. In patients with hepaticojejunostomy strictures, stone extraction into the intestine might be challenging even after performing hepaticojejunostomy stricture dilation using a balloon catheter. In such cases, transluminal stone removal is considered an alternative method. With transluminal stone removal, a small stone that escapes from the conventional basket or from a balloon catheter could migrate into the branch bile ducts. The novel spiral basket catheter available in Japan. The wires form a helix shape, wherein each wire is wound counterclockwise, and the winding pitch becomes gradually tighter from the proximal portion to the tip. As the winding pitch is smaller and the wires are in closer contact with the bile duct wall as compared with conventional basket catheter, small bile duct stones can be easily captured by simply pulling back the catheter while the basket is open. In addition, even during withdrawal inside the bile duct, a high retrieval performance is assured by the special design that maintains the opening width on the top end. Therefore, transluminal stone removal using this novel basket catheter might be clinically useful, although further prospective evaluation of a larger number of cases is needed.

Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10–treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.

Purpose The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. Methods This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients’ psychological status using the Hospital Anxiety and Depression Scale (HADS). Results The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was − 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). Conclusion MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

Background Baloxavir marboxil (baloxavir) is a single-dose, oral antiinfluenza drug with a novel mechanism of action. We compared the incidence of hospitalization in patients treated with baloxavir vs neuraminidase inhibitors. Methods In this retrospective, observational, cohort study, we used real-world patient data extracted from a Japanese health insurance claims database. The enrollment period was 1 October 2018 to 17 April 2019. On day 1, eligible patients (N = 339 007) received baloxavir, oseltamivir, zanamivir, or laninamivir. Baseline characteristics were standardized using the inverse probability of treatment weighting method. The primary end point was the incidence of hospitalization (days 2–14). Secondary end points included antibacterial use, secondary pneumonia, and additional antiinfluenza drug use. Results Compared with the baloxavir group, the incidence of hospitalization was greater in the oseltamivir group (risk ratio [RR] and 95% confidence interval [CI], 1.41 [1.00–2.00]; risk difference [RD] and 95% CI, 0.06 [.01–.12]) and zanamivir group (RR, 1.85 [1.23–2.78]; RD, 0.11 [.02–.20]). Oseltamivir-treated patients were less likely to require antibacterials than baloxavir-treated patients (RR, 0.87 [.82–.91]). However, oseltamivir-treated patients were more likely to be hospitalized with antibacterials (RR, 1.70 [1.21–2.38]) or antibacterial injection (RR, 1.67 [1.17–2.38]) than baloxavir-treated patients (post hoc analysis). Compared with baloxavir-treated patients, additional antiinfluenza drug use was greater in oseltamivir-, zanamivir-, and laninamivir-treated patients (RR, 1.51 [1.05–2.18], 2.84 [2.04–3.96], and 1.68 [1.35–2.10], respectively). Conclusions Baloxavir is an efficacious antiinfluenza treatment that may reduce hospitalization compared with oseltamivir and zanamivir. Clinical Trials Registration University hospital Medical Information Network Clinical Trials Registry (UMIN000038159)., Baloxavir marboxil is a single-dose oral antiinfluenza drug with a novel mechanism of action. This real-world data study indicates that baloxavir marboxil may reduce hospitalization after influenza outpatient treatment compared with neuraminidase inhibitor treatment.

Background Colloid carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreatic head with prominent calcification is exceedingly rare. Only a few studies about this entity have been reported in the literature. Therefore, its biological behavior, appropriate treatment modalities, and overall patient prognosis remain largely unclear. In this report, we present a case of a resected colloid carcinoma derived from IPMN with prominent calcification. In addition, we review the relevant literature and discuss the clinical management of colloid carcinoma derived from IPMN with prominent calcification, including the histopathological features. Case presentation A 75-year-old man presented with a pancreatic tumor measuring 58 mm on the head of the pancreas that was incidentally detected by abdominal ultrasonography. Abdominal computed tomography and endosonography revealed a multilobular cystic lesion with a 17 mm mural nodule in the pancreatic head. Furthermore, prominent calcification was observed on part of the cyst wall. Magnetic resonance cholangiopancreatography showed a multilobular cyst in the branch duct lacking communication between the cystic lesion and the main pancreatic duct. Thus, the lesion was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with a preoperative classification of T1N0M0 stage IA according to the 8th Union for International Cancer Control (UICC) guidelines, and the patient underwent conventional pancreatoduodenectomy. The resected specimen was microscopically found to contain colloid carcinoma, probably derived from IPMN. In addition, marked calcification was confirmed in the partition wall of the cystic mass. The postoperative course was uneventful, and no evidence of recurrence or metastasis was observed after 10 months of follow-up. Conclusions We consider that colloid carcinoma derived from IPMN should be differentially diagnosed as a pancreatic multilobular cystic lesion with prominent calcification that shows no sign of systemic chronic pancreatitis.

Objectives In this study, we revisited the reasons for poorer prognosis afterlivertransplantin patients with hepatitis C virus, whose main causes of death were generally known to be recurrent disease. Materials and methods Between April 2003 and March 2017, among 132 patients who underwent liver transplantbecause ofliver cirrhosis at ourinstitution, 40 patients (30.3%) were positive for hepatis C virus. We retrospectively compared the overall survival afterliver transplantin patients with and without hepatitis C virus infection. Furthermore, we investigated the causes of death in transplant recipients with hepatitis C virus infections. Results In patients with hepatitis C virus infection, overall survivalwas 82.2%, 75.2%, and50.8% at 1, 5, and 10 years,respectively, afterlivertransplant;these results were lower than those in patients without infection (94.5%, 87.0%, and 87.0% at 1, 5, and 10 years, respectively; P = .001). Among 40 patients with positive infection, 14 patients died after liver transplant. A main reason for death was hepatocellular carcinoma recurrence (3 patients). Surprisingly, only 1 patient died from hepatitis C virus-related complication (fibrosing cholestatic hepatitis); the remaining 10 patients died from reasons other than hepatitis C virus disease progression. Conclusions Our results suggest that clinicians should not only be aware of hepatitis C virus recurrence but should also be aware of other unrelated complications in transplant recipients who are positive for this virus.

Highlights • Endoscopically unresectable stage I esophageal cancer is usually treated by surgery. • Operable stage I esophageal carcinomas were treated with our multimodal approach. • Based on interim appraisal, most patients were treated with chemoradiotherapy. • Although local recurrences were common, half of them were rescued without surgery. • We observed favorable long-term survival and esophagus preservation rates., Background and purpose To assess the long-term outcomes of a multimodal approach for maximum esophagus preservation in operable patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma (ESCC). Materials and methods The medical records of patients with stage I thoracic ESCC treated with our protocol between 1992 and 2005 were retrospectively reviewed. Our protocol consisted of neoadjuvant concurrent chemoradiotherapy, followed by either additional definitive chemoradiotherapy for good responders (CRT group) or surgery for moderate or poor responders (CRT-S group) after an interim appraisal. Results A total of 51 patients were analysed. The median age of the patients was 67 years. The median follow-up period was 124.8 months. After the interim assessment, 49 and 2 cases were assigned to the CRT and CRT-S groups, respectively. In the intent-to-treat analyses, overall survival (OS), disease-free survival (DFS), cumulative incidence for death from esophageal cancer, and that for loss of esophageal function were 78.9%, 53.5%, 10.5%, and 20.4% at 5 years, and 55.2%, 27.8%, 18.2%, and 22.9% at 10 years, respectively. Grade 3 late toxicities occurred with the following incidences: esophageal stenosis in 1 case, esophageal ulcer in 1 case, and pericardial effusion in 2 cases. No grade 4 or higher toxicities were observed. Conclusion Long-term survival and esophagus preservation outcomes were favorable, with acceptable toxicities. Our results suggest that CCRT is an alternative treatment for majority of operable patients with endoscopically unresectable stage I thoracic ESCC in combination with salvage therapy.

Sepsis-induced endothelial acute respiratory distress syndrome is related to microvascular endothelial dysfunction caused by endothelial glycocalyx disruption. Recently, recombinant antithrombin (rAT) was reported to protect the endothelial glycocalyx from septic vasculitis; however, the underlying mechanism remains unknown. Here, we investigated the effect of rAT administration on vascular endothelial injury under endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 10-week-old male C57BL/6 mice, and saline or rAT was administered intraperitoneally at 3 and 24 hours after LPS administration. Subsequently, serum and/or pulmonary tissues were examined for inflammation and cell proliferation and differentiation by histologic, ultrastructural, and microarray analyses. The survival rate was significantly higher in rAT-treated mice than in control mice 48 hours after LPS injection (75% versus 20%; P

Background: The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia” (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown. Objectives: This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH. Methods: This study analyzed 380 clinically diagnosed subjects with heterozygous FH without any history of atherosclerotic cardiovascular diseases. Severe FH was defined as untreated low-density lipoprotein cholesterol >400 mg/dL, >310 mg/dL plus 1 high-risk feature, or >190 mg/dL plus 2 high-risk features according to IAS-proposed statement. The occurrence of first and subsequent composite outcomes (cardiac [cardiac death + coronary artery disease + coronary revascularization] and noncardiac events [stroke + peripheral artery disease] was compared between subjects with severe (n = 135) and non-severe (n = 227) FH. Results: Severe FH was identified in 40.3% of study population. They had higher low-density lipoprotein cholesterol (P < 0.001) and lipoprotein(a) (P = 0.03) levels. Moreover, they more frequently received high-intensity statin (P < 0.001), PCSK9 inhibitor (P < 0.001), and lipoprotein apheresis (P = 0.01) than nonsevere FH subjects did, which resulted in a lower on-treatment low-density lipoprotein cholesterol level of subjects with severe FH (113 ± 47.2 vs 130 ± 53.9 mg/dL; P = 0.007). However, during the 7.4-year observational period, subjects with severe FH exhibited a 9.3-, 15.4-, and 5.9-fold greater risk for first composite (P < 0.001), cardiac (P < 0.001), and noncardiac outcomes (P = 0.02), respectively. Multivariate Cox proportional hazard model consistently revealed the 7.8- and 7.9-fold elevated risks of first (P < 0.001) and of subsequent (P < 0.001) composite outcomes in subjects with severe FH. Conclusions: Japanese subjects with severe FH present profound risks of both first and subsequent atherosclerotic cardiovascular diseases in the primary prevention settings. These findings support the clinical applicability of IAS-defined severe FH in Japanese patients, which identifies those who require further stringent antiatherosclerotic management.

Endoscopic ultrasound-guided biliary drainage has been developed as an alternative method for biliary drainage. EUS-guided hepaticogastrostomy (EUS-HGS) can be attempted via the trans-gastric route. These procedures are technically complex for two reasons. First, puncture of the intrahepatic bile duct via the trans-gastric route can be more difficult than that by other approaches because of the small diameter of the target site, and guidewire insertion or manipulation is challenging during EUS-HGS. Second, critical adverse events, such as stent migration into the abdominal cavity, could occur because of the greater mobility of the stomach compared to the duodenum. Therefore, endoscopists should be cautious when performing EUS-HGS. An advantage of EUS-HGS is that it can be performed in patients with complications such as duodenal bulb obstruction or surgically altered anatomy. Recent advances in technique and improvements in devices and stents for EUS-HGS have shown promise for improving the technical success rate of EUS-HGS and reducing the rate of adverse events. However, endoscopists should remain aware of the possibility of critical adverse events such as stent migration.

To evaluate the effect of cryoprecipitate (CRYO) transfusion in women referred for postpartum hemorrhage (PPH). This retrospective cohort study included patients with primary PPH referred to Gifu University Hospital between April 2013 and March 2020. We analyzed the effect of CRYO transfusion on fluid balance 24 h after the initial examination using a multivariable linear regression model adjusted for several confounding variables. To evaluate whether outcomes were modified by active bleeding, an interaction term of CRYO*active bleeding was incorporated into the multivariable model. We identified 157 women: 38 in the CRYO group (cases) and 119 in the control group. Fluid balance in the aforementioned period tended to decrease in the CRYO group compared with that in the control group (coefficient − 398.91; 95% CI − 1298.08 to + 500.26; p = 0.382). Active bleeding on contrast-enhanced computed tomography affected the relationship between CRYO transfusion and fluid balance (p = 0.016). Other outcomes, except for the overall transfusion requirement, were not significantly different; however, the interaction effect of active bleeding was significant (p = 0.016). CRYO transfusion may decrease the fluid balance in the first 24 h in PPH patients, especially in those without active bleeding.

Aims/Introduction The aim of this study was to elucidate whether sodium–glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) of, Administration of sodium–glucose cotransporter 2 inhibitors slowed the annual estimated glomerular filtration rate decline in type 2 diabetes patients with an estimated glomerular filtration rate of

Spontaneous regression (SR) is defined as a complete or partial, temporary or permanent disappearance of a tumor without anticancer treatment, which potentially develops after surgery or biopsy for primary and metastatic tumors despite unknown incidence rate. Here, we report the incidence rate of SR after endobronchial ultrasound-guided transbronchial nodal needle aspiration (EBUS-TBNA) in lung cancer patients. Among 96 patients evaluable with chest CT before and after EBUS-TBNA, SR was found in three patients (3.1%). With regards to patient characteristics, two patients had small cell lung cancer (SCLC), and one patient had adenocarcinoma. All patients had stage 3 disease with a bulky N2 stage and a history of smoking. Two patients also had interstitial lung disease. Notably, SR was observed not only at the biopsied site, but also at the non-biopsied site. Our results indicate that SR can develop following EBUS-TBNA in a substantial proportion of lung cancer patients.