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COVID-19 was first confirmed in December 2019 in Wuhan, China and is now spreading worldwide. Diagnosis of COVID-19 is sometimes difficult due to the absence of symptoms and its tendency to be masked by other diseases. In this paper, we report a COVID-19 case in which diagnosis was delayed due to aspiration pneumonia. A 64-year-old man visited our department for evaluation of swallowing function. However, during the examination, the patient aspirated testing food and subsequently developed a fever. Based on his medical history and computed tomography (CT) images, he was diagnosed with aspiration pneumonia and admitted to the hospital to begin treatment. However, after admission, his respiratory condition deteriorated, and the result of a COVID-19 polymerase chain reaction (PCR) test was positive. Previous reports have shown that CT images in cases of COVID-19 pneumonia were normal in the early phase, and abnormalities usually appeared approximately 6–11 days after onset. Common findings of COVID-19 are consolidation, ground-glass opacities, and a distribution of lesions predominantly in the bilateral inferior lung field periphery. It is difficult to differentiate COVID-19 pneumonia from other types of pneumonia; it should therefore be listed as a differential diagnosis during the current pandemic.

4069 Background: BKM120 is an oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, which showed promising activity in breast cancer and squamous cell carcinoma of head and neck. We prospectively investigated clinical activity, safety and biomarkers of BKM120 in advanced esophagus squamous cell carcinoma (ESCC). Methods: We conducted a multicenter phase II study of BKM120 monotherapy in patients with pretreated advanced ESCC. All the patients had a treatment history of fluoropyrimidine and platinum. BKM120 of 100 mg/day was orally administered in a 28-day cycle. A primary end-point was a disease control rate (DCR). Using Simon’s minimax two-stage design, total of 41 patients were required for primary analysis (promising DCR of 60%, non-promising one of 40%, one-sided alpha level of 10% and power of 90%). The response rate (RR), progression-free survival (PFS), overall survival (OS), and safety were also evaluated as secondary endpoints. Tumor samples for all the patients were required for gene alternation analysis in comprehensive genomic profiling assay (FoundationOne). Results: A total of 42 patients (median age, 62.5 years; performance status 0/1 = 28/14) were enrolled. One ineligible patient was excluded from primary analysis. Nineteen and two patients had SD and unconfirmed PR. DCR was 51.2% (95% CI, 35.1% to 67.1%), which met the primary endpoint of the study. Median PFS and OS was 2.0 months (95% CI, 1.8 to 3.2 months) and 9.0 months (95% CI, 6.4 to 11.7 months), respectively. Common grade 3 or 4 adverse events were anorexia, rash, hyponatremia, lipase increased, and abnormal hepatic function (including increased transaminase levels), which were profiles similar to previous studies of BKM120 monotherapy. No treatment-related deaths occurred. Further analyses of the gene alternation are ongoing. Conclusions: BKM120 monotherapy showed promising efficacy and mild toxicity profile in patients with pretreated advanced ESCC. BKM120 is worth evaluating in a further confirmatory study. Result of subgroup analyses with respect to gene alternation status will be presented. Clinical trial information: UMIN000011217.

OBJECTIVE Radiotherapy (RT) carries a substantial risk for the development of osteoradionecrosis (ORN) of the jaw. This study was performed to investigate the relationship between dental extractions after RT and the development of ORN. MATERIAL AND METHODS Thirty-two patients with head and neck cancer who underwent tooth extraction after RT were investigated for correlations between the development of ORN and various factors. RESULTS Postextraction ORN was diagnosed in 12 (12.1%) teeth of 9 patients. The RT dose against the site of tooth extraction was 62.0 and 37.4 Gy in the ORN and Non-ORN groups, respectively (p

Coarse-grained reconfigurable architectures (CGRAs) provide high energy efficiency with word-level programmability rather than bit-level ones such as FPGAs. The coarser reconfigurability brings about higher energy efficiency and reduces the complexity of compiler tasks compared to the FPGAs. However, application mapping process for CGRAs is still time-consuming. When the compiler tries to map a large and complicated application data-flow-graph(DFG) onto the reconfigurable fabric, it tends to result in inefficient resource use or to fail in mapping. In case of failure, the compiler must divide it into several sub-DFGs and goes back to the same flow. In this work, we propose a novel partitioning method based on a genetic algorithm to eliminate the unmappable DFGs and improve the mapping quality. In order not to generate unmappable sub-DFGs, we also propose an estimation model which predicts the mappability and resource requirements using a DGCNN (Deep Graph Convolutional Neural Network). The genetic algorithm with this model can seek the most resource-efficient mapping without the back-end mapping process. Our model can predict the mappability with more than 98% accuracy and resource usage with a negligible error for two studied CGRAs. Besides, the proposed partitioning method demonstrates 53-75% of memory saving, 1.28-1.39x higher throughput, and better mapping quality over three comparative approaches.

Purpose To create an equation for predicting the trabecular iris angle (TIA) and to verify its accuracy after implantable collamer lens (ICL) implantation. Setting Nagoya Eye Clinic, Nagoya, Japan. Design Retrospective evaluation of a screening approach. Methods The subjects included 174 eyes (174 patients) that underwent ICL implantation. Patients were randomly assigned to the prediction equation group (116 eyes) or verification group (58 eyes). Anterior segment optical coherence tomography (AS-OCT; CASIA2 TOMEY) was performed before and 3 months after ICL surgery. For the prediction group, a prediction equation was created with the preoperative AS-OCT parameters and ICL size as independent variables and the postoperative anterior chamber depth (ACD) as dependent variables. Then, by applying the predicted post-ACD and preoperative AS-OCT parameters as independent variables and TIA after ICL surgery as the dependent variable, a prediction equation was created to predict the postoperative TIA (post-TIA) after ICL surgery. Each prediction equation was created using stepwise multiple regression analysis, and its accuracy was verified by a Bland-Altman plot in the verification group. Results The explanatory variables (standardized partial regression coefficient) selected in the post-TIA prediction equation were post-ACD (0.629), TIA750 (0.563), iris curvature (0.353), pupil diameter (-0.281), iris area (-0.249), and trabecular iris space area 250 (-0.171) (R2 = 0.646). There were no clinically significant systematic errors between measured and predictive post-TIA values in the verification group. The average absolute prediction error was 3.43° ± 2.22°. Conclusions Post-TIA can be accurately predicted from the predicted post-ACD and other preoperative AS-OCT parameters.

BACKGROUND AND AIM Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P

Although combination immune checkpoint inhibitor (immuno‐oncology [IO]) therapy is the first‐line treatment for metastatic renal cell carcinoma (mRCC), it mostly causes resistance and tumor regrowth. Therefore, an optimal second‐line therapy is necessary. Such therapy typically comprises vascular endothelial growth factor receptor‐tyrosine kinase inhibitors (VEGFR‐TKIs). This study was aimed at comparing the efficacy of two TKIs—axitinib and sunitinib—in mRCC patients. From January 2008 to October 2018, we registered 703 mRCC patients from 8 Japanese institutes. Of these, 408 patients received axitinib or sunitinib as the first‐line treatment. Thereafter, efficacy and survival rate were compared between the axitinib and sunitinib groups. To reduce the effects of selection bias and potential confounders, propensity score matching analysis was performed. Axitinib and sunitinib were administered in 274 and 134 patients, respectively. More than 25% of the patients received nivolumab sequence therapy. To calculate the propensity scores for each patient, we performed multivariate logistic regression analysis. The objective response rate, progression‐free survival (PFS), cause‐specific survival, and overall survival (OS) were significantly better in the axitinib group than in the sunitinib group. Furthermore, the OS was better in the nivolumab‐treated patients in the axitinib group. Axitinib showed higher efficacy and afforded greater survival benefits than did sunitinib when administered as first‐line therapy in mRCC patients. Thus, from among VEGFR‐TKIs, axitinib might be a possible option for application in the middle of IO drug‐based treatment sequences., Compared to sunitinib, axitinib showed higher efficacy and afforded greater survival benefits as first‐line therapy in patients with metastatic renal cell carcinoma. Axitinib might be better than sunitinib for application in the middle of IO drug‐based treatment sequences.

Objectives To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). Methods We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. Results After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25–2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. Conclusion Patients with those factors should be dealt with appropriate cautions to strike a risk–benefit balance of orthopedic surgeries.

ALK, ROS1, and RET kinase fusions are important predictive biomarkers of tyrosine kinase inhibitors (TKIs) in non‐small‐cell lung cancer (NSCLC). Analysis of cell‐free DNA (cfDNA) provides a noninvasive method to identify gene changes in tumor cells. The present study sought to use cfRNA and cfDNA for identifying fusion genes. A reliable protocol was established to detect fusion genes using cfRNA and assessed the analytical validity and clinical usefulness in 30 samples from 20 cases of fusion‐positive NSCLC. The results of cfRNA‐based assays were compared with tissue biopsy and cfDNA‐based liquid biopsy (Guardant360 plasma next‐generation sequencing [NGS] assay). The overall sensitivity of the cfRNA‐based assay was 26.7% (8/30) and that of cfDNA‐based assay was 16.7% (3/18). When analysis was limited to the samples collected at chemo‐naïve or progressive disease status and available for both assays, the sensitivity of the cfRNA‐based assay was 77.8% (7/9) and that of cfDNA‐based assay was 33.3% (3/9). Fusion gene identification in cfRNA was correlated with treatment response. These results suggest that the proposed cfRNA assay is a useful diagnostic test for patients with insufficient tissues to facilitate effective administration of first‐line treatment and is a useful tool to monitor the progression of NSCLC for consideration of second‐line treatments., cfRNA‐ and cfDNA‐based assays are evaluated in 20 cases of fusion‐positive NSCLC. cfRNA assay was superior to cfDNA assay for the detection of gene fusions. The results of the cfRNA assay were consistent with the therapeutic effect.

Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.

Aim Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease. Methods In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis. Results There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR (p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018). Conclusions Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

Background/purpose Tongue pressure plays an important role in swallowing function. The purpose of this study is to investigate whether decreased tongue pressure is associated with dysphagia and the development of pneumonia in the elderly requiring long-term care. Materials and methods Tongue pressure measurement and swallowing videoendoscopic (VE) examination were performed in 60 hospitalized elderly people (33 males and 27 females, with an average age of 84.3 years) to investigate the relationship with the clinical course. Factors related with dysphagia was analyzed by Fisher's exact test and one-way ANOVA, followed by multivariate logistic regression. The relationship between each variable and survival were analyzed by cox regression. Results Twenty-one patients had dysphagia by VE examination. Multivariate analysis showed that smaller BMI and reduced tongue pressure were significantly correlated with dysphagia. Smaller number of remaining teeth and dysphagia were significantly related to pneumonia-related death. No patients with tongue pressure of larger than 20 kpa died by pneumonia within one year, while in those with tongue pressure of smaller than 20 kpa, one-year cumulative survival rate by pneumonia was 44.3%. Conclusion Decreased tongue pressure was significantly associated with dysphagia and may increase the risk of pneumonia-related death in the elderly requiring long-term care.

BACKGROUND Acute myocardial infarction (AMI) patients with low body mass index (BMI) exhibit worse clinical outcomes than obese patients; however, to our knowledge, no prospective, nationwide study has assessed the effect of BMI on the clinical outcomes of AMI patients.Methods and Results:In this multi-center, prospective, nationwide Japanese trial, 2,373 AMI patients who underwent emergent percutaneous coronary intervention within 12 h of onset from the Japanese AMI Registry (JAMIR) were identified. Patients were divided into the following 4 groups based on their BMI at admission: Q1 group (BMI

Fanconi syndrome is a functional disorder of the proximal tubule, characterized by pan-aminoaciduria, glucosuria, hypophosphatemia, and metabolic acidosis. With the advancements in gene analysis technologies, several causative genes are identified for Fanconi syndrome. Several mitochondrial diseases cause Fanconi syndrome and various systemic symptoms; however, it is rare that the main clinical symptoms in such disorders are Fanconi syndrome without systematic active diseases like encephalomyopathy or cardiomyopathy. In this study, we analyzed two families exhibiting Fanconi syndrome, developmental disability and mildly elevated liver enzyme levels. Whole-exome sequencing (WES) detected compound heterozygous known and novel BCS1L mutations, which affect the assembly of mitochondrial respiratory chain complex III, in both cases. The pathogenicity of these mutations has been established in several mitochondria-related functional analyses in this study. Mitochondrial diseases with isolated renal symptoms are uncommon; however, this study indicates that mitochondrial respiratory chain complex III deficiency due to BCS1L mutations cause Fanconi syndrome with developmental disability as the primary indications.

Bejel, caused by Treponema pallidum subsp. Endemicum (TEN), is a locally transmitted disease among children and juveniles in hot and dry regions. The number of adult cases of TEN infection outside of endemic areas has recently increased. We clinically examined five cases of TEN infection among adult cases previously reported in Japan. TEN infection mainly developed among young to middle-aged men who have sex with men (MSM). The clinical features of cases of TEN infection were similar to those of primary- and secondary-stage T. pallidum subsp. pallidum (TPA) infection. Genital lesions were common as the primary lesion. The clinical features and laboratory parameters of cases of TEN infection were similar to those of TPA infection. Most of the isolated strains had the A2058G mutation in 23S rDNA, which is responsible for resistance to macrolides. We also performed the systemic literature review of the TEN cases outside the endemic countries. The recent reported cases diagnosed with molecular methods shared the clinical features, occurred in young-to middle-aged sexually active persons in urban areas of developed countries and often accompanied with genital lesions, which were distinct from the classic description of bejel. This case series and the literature review provides important clinical insights and will contribute to the clinical detection of this rarely identified disease in developed countries. The surveillance of treponematoses, including TEN infection, using molecular diagnostic techniques is also warranted in developed countries, for the purpose of grasping the epidemic situation and control the local transmission.

Objective To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis. Conclusion A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

The prognostic significance of combining intra-aortic balloon pumping (IABP) with extracorporeal membrane oxygenation (ECMO) for acute myocardial infarction (AMI) patients is still unclear. We investigated whether combining IABP with veno-arterial (VA)-ECMO is associated with a lower risk of short-term mortality.Among 12,093 AMI cases enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS), we identified 519 who were administered VA-ECMO during hospitalization. Among these, 459 received IABP support (IABP group) and 60 cases did not (no-IABP group). The primary endpoint was 30-day all-cause death; the secondary endpoint was major bleeding. Logistic regression analysis using original data was conducted. We also established weighted logistic regression models with inverse probability of treatment weighting (IPTW).Logistic regression analysis revealed that IABP use was significantly associated with a reduced risk of 30-day death in the original data [odds ratio (OR) 0.504, 95% confidence interval (CI) 0.282-0.901, p = 0.021]. After IPTW-adjustment for clinically relevant covariates with the use of IABP, patients receiving VA-ECMO with IABP had a lower risk of 30-day death (OR 0.816, 95% CI 0.746-0.892, p0.001) compared to those without IABP. The incidence of major bleeding was comparable between the groups (IABP 29.0% vs. non-IABP 21.7%, p=0.302). However, the risk of major bleeding was higher in the IABP group after IPTW-adjustment (OR 1.092, 95% CI 1.008-1.184, p=0.032).IABP support for AMI patients with VA-ECMO was significantly associated with reduced risk of short-term mortality, suggesting that the addition of IABP support might contribute to improved survival in AMI patients requiring VA-ECMO.

A 77-year-old man complained of postmeal vomiting and sustained general fatigue. An abdominal computed tomography scan showed massive gastric expansion and fluid storage. Gastroscopy revealed four gastric bezoars that were considered to have caused pyloric ring obstruction. The patient was asked to drink 500 mL per day of Coca-Cola® for 4 days. On the fourth day, we performed endoscopic crushing and removal by injecting Coca-Cola®, cutting the softened bezoar with endoscopic snares, and collecting the pieces with endoscopic nets. We herein report (with a video presentation) a rare case of tannin-phytobezoars endoscopically removed with the administration and injection of Coca-Cola®.

Background and Aims To clarify the relationship between metabolic dysfunction‐associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Methods The participants were divided into four groups by the presence or absence of fatty liver disease (FLD) and metabolic dysfunction (MD). MAFLD was defined as having both FLD and MD, whereas CKD was defined as having an estimated glomerular filtration rate of

Background:This research aimed to determine whether patterns of temporal changes in activity levels can indicate postoperative complications following hepatectomy., Methods:Between December 2016 and December 2019, 147 patients wore an accelerometer to measure their physical activity levels after hepatectomy until postoperative day 7. Patterns of changes in activity levels were categorized as follows: upward slope type (n = 88), wherein activity levels gradually increased; bell curve type (n = 13), wherein activity levels initially increased but subsequently decreased; and flat type (n = 46), wherein there was no apparent increase in activity levels. Patient characteristics and postoperative complications were compared for each group., Results:Postoperative complications occurred in 4.5% of patients in the upward slope group, in 76.9% in the bell curve group, and in 65.2% in the flat group (p < 0.001). Surgical site infections (SSI), refractory pleural effusion, and ascites were more common in the bell curve group, while pneumonia was only observed in the flat group., Conclusion:SSI, pleural effusion, and ascites should be considered when previously increasing activity levels decline during the postoperative period. In addition, there is a high risk of SSI and pneumonia when activity levels do not increase at all after surgery.

Alzheimer’s disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. Centella asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. Centella asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, Centella asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that Centella asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.

We report a case of mantle cell lymphoma mimicking Castleman disease. A 76-year-old man presented with generalized lymphadenopathy, splenomegaly, anemia, polyclonal gammopathy, and pulmonary infiltrations. Lymph node biopsy revealed histological features of hyaline vascular Castleman disease. Treatment with prednisolone induced lymphocytosis with immunophenotypic and genetic features of mantle cell lymphoma. A detailed immunohistochemical study of the lymph node demonstrated a mantle cell lymphoma-mantle zone growth pattern. Glucocorticoid-induced distribution lymphocytosis has not been reported in mantle cell lymphoma. Careful observation of circulating lymphocytes during steroid treatment may enable diagnosis of the underlying occult lymphoma in a subset of patients exhibiting clinical manifestations of Castleman disease.

Primary lung cancer was suspected in three patients upon chest computed tomography (CT) and bronchoscopy. Wash cytology revealed that all patients had lesions categorized as class III or lower (Papanicolaou classification), and the wash solution was then subjected to an epidermal growth factor receptor (EGFR) mutation search. As a result, exon 19 deletion was found in two patients, whereas an exon 21 L858R mutation was found in one. Therefore, all three patients underwent surgery without pathological evidence, and surgical pathology subsequently confirmed the diagnosis of primary lung adenocarcinoma. As observed, EGFR mutation testing was useful for cancer diagnosis.

PURPOSE To investigate the accuracy of a segment-counting method in predicting lung function and volume after stapler-based thoracoscopic segmentectomy in comparison with lobectomy. METHODS Between 2014 and 2018, patients who underwent these procedures were retrospectively reviewed. Thoracic computed tomography and spirometry data before and 1 year after the surgery were assessed. We evaluated the differences between the predicted values using a segment-counting method and the actual postoperative values for lung function and volume in each group. Sub-analyses were also performed to assess the impact of the number of staples and resected segments in predicting patient outcomes. RESULTS We included 116 patients (segmentectomy, 69; lobectomy, 47). Actual postoperative lung function and volume values matched the predicted values in the stapler-based segmentectomy group, and significantly exceeded the predictions in the lobectomy group (P

Introduction: Condoliase is a newly approved drug that improves symptoms associated with lumbar disk herniation (LDH) by intradiscal administration. This study aimed to evaluate the mid-term outcomes of condoliase injection, examine the adverse events, including cases that required surgery after condoliase administration, and verify cases in which condoliase could be effective. Methods: We enrolled patients with LDH who were treated conservatively for at least six weeks and received condoliase. We assessed the visual analog scale (VAS) score, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, disk height, and disk degeneration for up to 6 months, and we examined the complications. Furthermore, a 50% or more improvement in leg pain VAS score was considered effective. Factors related to symptom improvement were investigated by determining whether lower limb pain improved in six months. Results: In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ±> 17.1 [16-86 years]). The duration of illness was 6.7 ±> 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness. Conclusions: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration.

A 62-year-old woman with a history of lung resection for lung cancer was admitted to our hospital due to cough, which became progressively more severe. She was diagnosed with chronic empyema with bronchopleural fistula (BPF) of the right upper bronchial stump. Although a pedicled muscle flap was transposed to the empyema cavity, the fistula remained. We used a vacuum-assisted closure system after open-window thoracotomy and observed the cavity reduction with expansion of the transposed muscle flap. We quantitatively evaluated the dynamics of the cavity change using a three-dimensional image analysis system. A reduction of the volume of the muscle flap by prolonged empyema and expansion of the muscle flap was observed immediately after vacuum-assisted management. However, expansion of the right residual lung was not recognized. Pedicled muscle flap transposition followed by vacuum-assisted management after open-window thoracotomy may be effective for treating chronic empyema caused by BPF.

In this study, we aimed to determine the association of neonatal/post-neonatal hypothyroidism with mother's iodine exposure, especially povidone iodine disinfection, and hysterosalpingography. Participants were mother-child pairs in a Japanese birth cohort (n = 100,286). Risk factors of hypothyroidism were supplement intake, seaweed intake, other daily iodine intake, povidone iodine disinfection at delivery, and maternal history of hysterosalpingography, thyroid disease (Graves' disease and Hashimoto's thyroiditis), and medication (thiamazole and levothyroxine). Congenital hypothyroidism (CH) at age 1 year was assessed using a questionnaire. Transient hypothyroidism was defined as elevated thyroid stimulating hormone level at birth and absence of CH at age 1 year. The incidence of CH at age 1 year per 100 children was 1.1 for those born at 22-30 weeks' gestation, 0.17 following povidone iodine disinfection, and 0.07, 0.95, 0.81, 1.17, and 1.15 with a maternal history of hysterosalpingography, Graves' disease, Hashimoto's thyroiditis, thiamazole use, and levothyroxine use, respectively. Odds ratios (95% confidence intervals) of CH at age 1 year for povidone iodine disinfection, hysterosalpingography history, maternal Graves' disease, and maternal Hashimoto's thyroiditis were 1.13 (0.71-1.79), 0.47 (0.07-3.36), 7.06 (3.70-13.5), and 5.93 (2.90-12.1), respectively. For transient hypothyroidism for povidone iodine disinfection and hysterosalpingography history, these values were 1.99 (1.51-2.62) and 0.63 (0.20-1.96), respectively. Maternal thyroid disease greatly increased neonatal/post-neonatal hypothyroidism risk. Povidone iodine disinfection may increase transient hypothyroidism risk but not the risk at 1 year of age. Hysterosalpingography does not increase hypothyroidism risk from birth to age 1 year.

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 Anastomotic disorder of the reconstructed gastric conduit is a life‐threating morbidity after thoracic esophagectomy. Although there are various reasons for anastomotic disorder, the present study focused on dislocation of the gastric conduit (DGC). Methods The study cohort comprised 149 patients who underwent transthoracic esophagectomy. The relationships between DGC and peri‐ and postoperative morbidities were analyzed retrospectively. Data were analyzed to determine whether body mass index (BMI) and extension of the gastric conduit were related to DGC. Uni‐ and multivariate Cox regression analyses were performed to identify the factors associated with anastomotic disorder. Results DGC was significantly related to anastomotic leakage (P, Anastomotic disorder is a life‐threating morbidity after esophagectomy. Anastomotic leakage, stricture, and mediastinal abscess/empyema are significantly related to dislocation of the gastric conduit.

Objective This study aimed to evaluate satisfaction with total joint replacement (TJR) surgery among patients with rheumatoid arthritis (RA). Methods We mailed questionnaires to randomly selected members of the Japan Rheumatism Friendship Association, stratified by age and prefecture, throughout Japan. The questionnaire collected demographic and clinical characteristics as well as patients’ satisfaction with TJR and their current therapy. Results Of the 1156 patients who returned the questionnaire, 339 (29.3%) responded that they had had TJR of any type. The mean age was 66.6 years, and 94.4% were women. The mean time period from the hip and knee TJR was 14–15 years. Over half of the patients who had had TJR were satisfied with the results, especially those who had had hip (89.6%) and knee TJR (87.3%), who reported a high level of satisfaction. Multivariable linear regression analysis revealed that, in patients with knee TJR, satisfaction with current therapy was significantly related to whether they were satisfied with the results of the surgery. Conclusion Most patients with RA who had undergone TJR were satisfied with the results even after a long period of time, and their level of satisfaction was associated with their satisfaction with current therapy.

Objectives This study aimed to evaluate the impact of exercise therapy on patient-reported outcomes (PROs) in rheumatoid arthritis (RA) as part of the process of updating the 2020 Japanese guidelines for the management of RA according to the Grading of Recommendations, Assessment, Development, and Evaluation system. Methods We searched PubMed, Japana Centra Revuo Medicina Web, and the Cochrane Library (from 2009 to 2018) to identify articles that evaluated PROs of exercise therapy and RA disease activity. Results A total of 662 articles were identified, including nine RCTs, and meta-analyses were performed on six RCTs on systemic exercise therapy and three RCTs on upper extremity exercise therapy. Analyzed exercise therapies were diverse, differing in target population, intervention method, and duration. Significant improvements were observed in the Health Assessment Questionnaire Disability Index (mean difference −0.35, 95% confidence interval (CI): −0.60 to −0.10), pain (standardized mean difference −2.04, 95% CI: −3.77 to −0.32), and SF-36. For upper extremity exercise therapy, significant improvements in PROs (Disabilities of the Arm, Shoulder, and Hand Questionnaire, Michigan Hand Outcome Questionnaire) were observed. Conclusion Exercise therapy in RA treatment improves patient subjective assessment of pain, physical function, and quality of life.

Background/aim Annals of Geriatric Medicine and Research held its inaugural international editorial board virtual meeting on September 16, 2021, to brainstorm ideas for sustainable growth. This special article summarizes the key concepts obtained from the webinar proceedings, with further development of ideas from ensuing discussions occurring after the meeting. Methods From the initial discussion points provided by eight editorial board members, including six presenters, email discussions further enriched these ideas to construct the current special article. The key points discussed were: 1) impactful research and impact factors, 2) international and Asian perspectives, and 3) challenges to sustainable growth. Results The editors noted the existing gap between the impact factor and research impact as a challenge for the growth paths of regional journals. However, they agreed that persevering with impactful research would ultimately translate into parallel and gradual gains in impact, which is, therefore, consistent with the organic growth of the journal. Acknowledging challenges in navigating between unique Asian perspectives and international outlooks, the editors encouraged academic journals to serve as bridges linking international evidence with the richness of local perspectives. For sustainable growth, the editors suggested that journals may be forged into the academic ecosystems of the region, diversify value streams, and establish themselves as reputable brands in disciplines. Conclusion By combining these discussions, we proposed the 'IMPACT' strategy for journals on the growth path in the region, which stands for 1) IMmersive user experience encompassing authors, reviewers, and readers; 2) Pasteur's quadrant use-inspired research; 3) Asia-Pacific context; 4) Collaborative; and 5) Translation to practice and policy.

Key Points A total of 137 patients with JMML were analyzed using DREAM.We developed a robust DNA methylation test that is highly consistent with the array-based international consensus definition for JMML., Visual Abstract, Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm that develops during infancy and early childhood. The array-based international consensus definition of DNA methylation has recently classified patients with JMML into the following 3 groups: high (HM), intermediate (IM), and low methylation (LM). To develop a simple and robust methylation clinical test, 137 patients with JMML were analyzed using the Digital Restriction Enzyme Analysis of Methylation (DREAM), which is a next-generation sequencing–based methylation analysis. Unsupervised consensus clustering of the discovery cohort (n = 99) using DREAM data identified HM (HM_DREAM; n = 35) and LM subgroups (LM_DREAM; n = 64). Of the 98 cases that could be compared with the international consensus classification, 90 HM (n = 30) and LM (n = 60) cases had 100% concordance with DREAM clustering results. Of the remaining 8 cases comprising the IM group, 4 were classified as belonging to the HM_DREAM group and 4 to the LM_DREAM group. A machine-learning classifier was successfully constructed using a support vector machine (SVM), which divided the validation cohort (n = 38) into HM (HM_SVM, n = 18) and LM (LM_SVM; n = 20) groups. Patients with the HM_SVM profile had a significantly poorer 5-year overall survival rate than those with the LM_SVM profile. In conclusion, we developed a robust methylation test using DREAM for patients with JMML. This simple and straightforward test can be easily incorporated into diagnosis to generate a methylation classification for patients so they can receive risk-adapted treatment in the context of future clinical trials.

Purpose: Auditory-perceptual evaluation is essential for the assessment of voice quality. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) provides a standardized protocol and assessment form for clinicians to analyze the voice quality and has been adapted into several different languages. The aims of this study were to develop the Japanese version of the CAPE-V and to investigate its reliability and validity. Method: The Japanese CAPE-V consisted of the same three speech contexts (vowels, sentences, and conversation) as developed in the original English version. The sentences were designed according to the concepts of the original version and reviewed by Japanese phoneticians. To validate the usefulness of the Japanese CAPE-V, voices of 173 Japanese-speaking subjects (76 subjects with dysphonia and 97 without voice complaints) were evaluated by five experienced judges, according to the Japanese CAPE-V as well as the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. Results: The Japanese CAPE-V provided a high interrater reliability (intraclass correlation coefficients [ICCs] > .85 for all the parameters) as well as a high intrarater reliability (ICCs > .85 for all the parameters). In addition, overall severity, roughness, and breathiness in the Japanese CAPE-V were highly correlated with the corresponding dimensions in the GRBAS scale, having Spearman correlation coefficients greater than .8. Conclusion: This study demonstrated the reliability and validity of the newly developed Japanese CAPE-V as an auditory-perceptual evaluation instrument.

We report on SiC pn-junction diodes with a high blocking voltage over 3 kV. Although SiC radiation sensors have been developed with a Schottky barrier type due to a simple fabrication process in the early stages, pn junction structures are advantageous due to lower sensitivity of the surface defects. Thus, this system provides an ideal condition to investigate the effect of bulk crystal defects on the characteristics of the radiation sensor. The pn diodes were designed with a device simulator and fabricated with a 4-inch 4H-SiC wafer. The epitaxial layer was grown on an n-type substrate with sufficiently low doping concentration of Nd-Na =~ 5 × 1014 cm..3 and an average thickness of 52 μm. Fabricated pn diodes with a relatively large leakage current still show a clear peak of the Landau distribution in the charge spectrum, suggesting their practical availability as minimum ionizing particle detectors. The estimated electron-hole pair creation energy is consistent with the published studies and we expect good radiation tolerance. Feasibility based on the wafer processing indicates that the prototype devices are a good candidate for the muon beam monitor application in the coherent muon-to-electron transition experiment (COMET) at J-PARC.

Introduction: We developed a new treatment method that combines tympanoplasty with transplantation of autologous cultured nasal mucosal epithelial cell sheets to regenerate the mucosa of patients with adhesive otitis media, which has been difficult to treat effectively. We verified whether this procedure could be performed safely and measured its therapeutic efficacy. Methods: Autologous nasal mucosal epithelial cell sheets were manufactured at a good manufacturing practice-compliant cell processing facility using autologous nasal mucosal tissue. We performed tympanoplasty and transplanted the cell sheets into the middle ear cavity in six patients with adhesive otitis media. Results: The manufactured autologous cultured epithelial cell sheets met the predetermined quality standards and were successfully transplanted safely in all cases. Computed tomography findings after cell sheet transplantation showed that aeration in the tympanic cavity was maintained or restored in five of the six patients (83.3%). Four of the six (66.7%) patients had postoperative air-bone gap within 20 dB, which is considered a postoperative success in tympanoplasty for chronic middle ear disease. Conclusions: The results of this clinical study suggest that tympanoplasty with cell sheet transplantation can be used to treat adhesive otitis media by reliably preventing re-adhesion of the tympanic membrane.

Introduction We previously reported a new cell transplantation therapy for patients with intractable otitis media using autologous nasal mucosal epithelial cell sheets, manufactured using temperature-responsive cell culture inserts. The current study aimed to verify whether the transplantable cell sheets could be manufactured for application in clinical trials, according to standard operational procedures (SOP), in a cell processing facility (CPF). Methods Human nasal mucosal epithelial cells from four volunteer donors were aseptically cultured and transplantable cell sheets successfully manufactured, with reproducibility, using temperature-responsive cell culture inserts in the CPF. During the manufacture of cell sheets, the CPF environment was confirmed to be aseptic by sterilization tests. Purity of the cell sheets was confirmed by histological analysis and flow cytometry. Both safety and quality of the human nasal mucosal epithelial cell sheets were validated. Results The cultured and manipulated human nasal mucosal epithelial cells showed no evidence of malignant transformation in vitro. The study confirmed the safety and suitability of the manufactured human nasal mucosal epithelial cell sheets for use in clinical trials. Conclusions The results led to the establishment of a coherent system in which transplantation could be achieved smoothly.

To retrospectively evaluate our treatment algorithm and surgical approaches for nasal fibro-osseous lesions at our hospital. Fifteen patients with nasal fibro-osseous lesions treated from January 1, 2010, to January 31, 2020 were included. Among them, 13 patients who underwent surgery were divided into groups A and B, based on whether they were treated before or after the treatment algorithm was established. The extent of the lesion, surgical approach, and outcomes, including bone regrowth assessed postoperatively using computed tomography at 6 months, were analyzed. In group A, six cases were treated via endoscopy and two via a combined endoscopy and external approach. In group B, three cases were treated via endoscopy, one via combined endoscopy and external approach, and one combined with craniotomy. Two group A cases and no group B cases had residual lesions postoperatively. Postoperative bone regrowth occurred in three group A patients and no group B patients. Multi-angled approaches for nasal fibro-osseous lesions based on the unified treatment algorithms used in the study may lead to a reduction in postoperative recurrence and complication rates.

Purpose: Impact of previous history of choledochojejunostomy (PCJ) on the incidence of organ/space surgical site infection (SSI) after hepatectomy remains unclear. The aim of this study was to investigate the incidence and causes of SSI after hepatectomy. Methods: Patients who underwent hepatectomy of ≤1 Couinaud's sector between January 2011 and September 2019 were retrospectively analyzed. Incidence of and risk factors for organ/space SSI (Clavien-Dindo grade ≥2) after hepatectomy were investigated. Results: Among 750 hepatectomies, 18 patients (2.4%) had a medical history of PCJ. Incidence of organ/space SSI was higher in patients with PCJ (50%) than in those without PCJ (3%, P

Background The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand‐1 (PD‐L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. Methods From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD‐L1 status and age, sex, stage, histological type, and prognosis were investigated. Results PD‐L1‐positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD‐L1‐positive PSC cases, two showed high PD‐L1 expression in the vimentin‐positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD‐L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD‐L1 staining in the sarcomatoid survived, whereas the other with negative PD‐L1 staining did not. Conclusion The present study showed that sarcomatoid carcinoma had a higher PD‐L1 expression compared to non‐small‐cell lung cancer and that both PSC and MPM tended to exhibit PD‐L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results., In malignant pleural mesothelioma (MPM) and pulmonary sarcomatoid carcinoma (PSC), which are thoracic mesenchymal malignant tumors, programed cell death ligand‐1 (PD‐L1) was positive in the vimentin‐positive part or the sarcomatoid area, found to be clinicopathologically significant. In MPM, the effectiveness of immune checkpoint inhibitors (ICIs) has been shown, especially in nonepithelioid type. Our results support the possibility that ICIs will work as well as MPM if PSC is also positive for PD‐L1 and has mesenchymal features such as vimentin‐positive or sarcomatoid compartments.