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Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. Robust historical control data are important in clinical trials of rare cancers such as chondrosarcoma in order to show a clear benefit of new drugs. However, it remains controversial whether IDH mutation status is associated with the clinical outcome of chondrosarcoma, and this hinders the development of mutant IDH inhibitors in clinical trials.background METHODS: We investigated the relationship between IDH gene status and clinicopathological data in 38 chondrosarcoma patients from whom frozen tumor samples were obtained at the time of biopsy or surgery. Targeted next-generation sequencing was also performed to compare genetic alterations between patients with and without IDH mutations.The results revealed 15 cases (40%) of heterozygous IDH1 mutations and five cases (13%) of IDH2 mutations. IDH-mutant chondrosarcoma was associated with worse overall survival than IDH-wild-type chondrosarcoma (IDH1/2 Mut vs. IDH Wt, P = 0.006; IDH1 Mut vs. IDH Wt, P = 0.030; IDH2 Mut vs. IDH Wt, P 0.0001). IDH mutation was also a significant poor prognostic factor both in univariate (P = 0.026) and multivariate (P = 0.048) analyses. Targeted next-generation sequencing revealed that characteristic mutations in chondrosarcoma, including TP53 and COL2A1, were more common in the IDH-mutant group than in the IDH-wild-type group.results CONCLUSION: This study is the first to report in detail the characteristics and clinical courses of IDH-mutant chondrosarcoma patients in Japan. Our data suggested that IDH-mutant chondrosarcomas might have a worse prognosis than that of IDH-wild-type chondrosarcoma, possibly through the more aggressive characters after metastasis. This information will be useful for designing clinical trials of mutant IDH inhibitors for treatment of advanced chondrosarcoma.

Objective To clarify the relationship between oral lichen planus (OLP) and systemic oxidative stress, we examined serum antioxidant and urinary oxidative stress marker levels in patients with OLP. Methods Fifteen female patients with clinical and histopathological diagnoses of OLP were enrolled in this study. The mean patient age was 67.6 years (range, 56–81 years). Ten age- and sex-matched volunteers without oral mucosal lesions were selected as a control group. Serum levels of the antioxidants vitamin A, vitamin C, vitamin E, folate, zinc, uric acid, and superoxide dismutase activity were evaluated. Urinary levels of the oxidative stress marker 8-hydroxy2’-deoxyguanosine (8-OHdG) were measured by enzyme immunoassays. All values were compared between the two groups. Results The mean value of serum vitamin C was lower in the OLP group (5.73 ± 2.34μg/mL) than in the control group (9.22 ± 3.65 μg/mL; P = 0.0125). Serum levels of vitamin A, vitamin E, folate, zinc, uric acid, and superoxide dismutase activity did not significantly differ between the two groups. The mean values of creatinine adjusted urinary 8-OHdG were 10.1 ± 7.34 ng/mg creatinine in the OLP group and 13.7 ± 12.7 ng/mg creatinine in the control group; these values did not significantly differ between the two groups (P = 0.5189). Conclusion Our results suggested that serum levels of vitamin C are low in patients with OLP. However, oxidative stress (determined by measurement of urinary 8-OHdG level) was not significantly higher in patients with OLP. Thus, the relationship between OLP and systemic oxidative stress was not fully elucidated in this study.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Introduction Adults from racial and ethnic minorities and low-income groups are disproportionately affected by vaccine-preventable diseases. The objective of this study is to examine the trends in adult vaccination coverage in the U.S. by race/ethnicity and SES from 2010 to 2019. Methods Temporal trends in influenza; pneumococcal; herpes zoster; and tetanus, diphtheria, and acellular pertussis vaccination coverage were examined by race/ethnicity and SES in 2020 using the National Health Interview Surveys from 2010 to 2019. Results Influenza vaccination coverage differed by race/ethnicity among adults aged ≥65 years (61.4% for Black, 63.9% for Hispanic, 71.9% for Asian, and 72.4% for White adults). Race/ethnicity, household income, education level, and health insurance type were significantly associated with receipt of influenza; pneumococcal; tetanus, diphtheria, and acellular pertussis; and zoster vaccinations among adults aged ≥65 years in a multivariable-adjusted regression model. Socioeconomic differences in influenza vaccine uptake narrowed among adults aged 18–64 years from 2010 to 2019. By contrast, racial/ethnic and socioeconomic differences in vaccine uptake persisted from 2010 to 2019 among adults aged ≥65 years. Conclusions Racial and ethnic disparities in vaccine uptake persisted over the last decade. Socioeconomic disparities in influenza vaccine coverage narrowed among adults aged 18–64 years; however, disparities persisted among adults aged ≥65 years. Efforts are urgently needed to achieve equity in immunization rates.

Currently, there are many methods to evaluate the effectiveness of manual lymph drainage in the treatment of lymphedema, that is, limb volume measurement, bio-electrical impedance measurement, computer tomography, and ultrasound imaging. However, it is difficult for these methods to accurately address the lymph flow generated by manual lymph drainage. Therefore, we aimed at developing a concise and accurate method to measure the lymph flow through the thoracic duct in human subjects, which is applicable for evaluating the effectiveness of manual lymph drainage. In the present mini-review, we demonstrate the developed method in detail and its scientific evidence for the effectiveness obtained with animal and human clinical experiments. In rat

BACKGROUND Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results:This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P

Objectives The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-ph...

Lateral pelvic lymph node dissection for rectal cancer is challenging due to the complexity of the pelvic wall anatomy, and incomplete lateral pelvic lymph node dissection may result in local recurrence in the lateral pelvis. Although 3-dimensional printed organ models are useful for understanding spatial anatomy, it is currently unclear whether they improve surgical outcomes.We aimed to assess whether the surgical effectiveness of lateral pelvic lymph node dissection is increased by the use of individualized 3-dimensional printed pelvic models.This was a retrospective study using a propensity matching analysis.This study was conducted at a university hospital in Japan.In total, 115 patients comprising 184 pelvic sides (right, 85 sides; left, 99 sides) who underwent lateral pelvic lymph node dissection for colorectal adenocarcinoma between January 2012 and December 2019 were enrolled.We compared surgical outcomes using 3-dimensional printed pelvic models with control outcomes.The primary outcome was the number of harvested lateral pelvic lymph nodes on 1 pelvic side after the propensity matching analysis.After matching, 35 pelvic sides each were allocated to the 3-dimensional model and control groups, and no significant differences were observed in patient characteristics between the 2 groups. The number of harvested lateral pelvic lymph nodes was significantly higher in the 3-dimensional model group (median, 9; range, 3-16) than in the control group (median, 6; range, 0-22; p = 0.047).This was a retrospective study using propensity score matching. However, historical backgrounds were not matched, and the majority of lateral pelvic lymph node dissection procedures in the 3-dimensional model group were recently performed. This limitation may have influenced surgical outcomes.The present study demonstrated that, by referring to individualized 3-dimensional printed pelvic models, colorectal surgeons harvested a larger number of lateral pelvic lymph nodes during lateral pelvic lymph node dissection. This result suggests that 3-dimensional printed models help surgeons to complete more detailed procedures. See Video Abstract at http://links.lww.com/DCR/B776.ANTECEDENTES:La disección lateral de los ganglios linfáticos de la pelvis en el cáncer de recto es un desafío debido a la complejidad de la anatomía de la pared pélvica; la disección incompleta de las mismas puede resultar en una recidiva local en dicha zona. Aunque la impresión tridimensional de modelos de órganos es útil para comprender la estructura anatómica espacial, actualmente no está claro si mejoran los resultados quirúrgicos.OBJETIVO:Nuestro objetivo fue evaluar si la efectividad quirúrgica de la disección de los ganglios linfáticos laterales de la pelvis aumenta mediante el uso individualizado de modelos pélvicos impresos en 3D.DISEÑO:Este fue un estudio retrospectivo que utilizó un análisis de coincidencia de propensión.AJUSTE:Este estudio se realizó en un hospital universitario de Japón.PACIENTES:En total, se enrolaron 115 pacientes que comprendían 184 lados pélvicos (85 de lado derecho; 99 de lado izquierdo) que fueron sometidas a disección lateral de ganglios linfáticos de la pelvis por adenocarcinoma colorrectal entre enero de 2012 y diciembre de 2019.INTERVENCIONES:Comparamos los resultados quirúrgicos mediante modelos pélvicos tridimensionales impresos con los resultados de control.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el número de ganglios linfáticos laterales pélvicos extraídos en un lado pélvico después del análisis de coincidencia de propensión.RESULTADOS:Después del emparejamiento, se asignaron 35 lados pélvicos cada uno, tanto al modelo tridimensional como al grupo de control; no se observaron diferencias significativas con respecto a las características de los pacientes entre los dos grupos. El número de ganglios linfáticos pélvicos laterales extraídos fue significativamente mayor en el grupo del modelo tridimensional (mediana, 9; rango 3-16) que en el grupo de control (mediana, 6; rango, 0-22) (p = 0.047).LIMITACIONES:Este fue un estudio retrospectivo que utilizó el emparejamiento por puntuación de propensión. Sin embargo, antecedentes históricos no fueron encontrados y la mayoría de los procedimientos de disección de los ganglios linfáticos laterales pélvicos en el grupo del modelo tridimensional se realizaron recientemente. Esta limitación pudo haber influido en los resultados quirúrgicos.CONCLUSIONES:El presente estudio demostró que al referirse a modelos pélvicos individualizados impresos en 3D, los cirujanos colorrectales recolectaron un mayor número de ganglios linfáticos laterales de la pelvis durante la disección lateral. Este resultado sugiere que los modelos tridimensionales impresos ayudan a los cirujanos a completar procedimientos más detallados. Consulte Video Resumen en http://links.lww.com/DCR/B776.

Acute decompensated heart failure (ADHF) due to severe aortic stenosis (AS) and concomitant left ventricular outflow tract (LVOT) obstruction is a serious condition. Treatment with medication alone is sometimes difficult, and the efficacy of further interventional strategies has not been fully elucidated. In patients with high surgical risks, combination therapy using transcatheter aortic valve replacement (TAVR) and percutaneous alcohol septal ablation (ASA) is used as a non-surgical intervention. However, this treatment cannot be performed under unstable hemodynamic conditions. This report highlights the utility and efficacy of emergent balloon aortic valvuloplasty (BAV) in controlling heart failure and its potential to serve as a bridge to curative therapy, even in older patients with ADHF due to severe AS with concomitant LVOT obstruction. Furthermore, combination therapy with TAVR and percutaneous ASA could be safely performed after controlling for ADHF using BAV. Non-surgical management is a more feasible treatment option in older patients with ADHF who are at higher risk of complications during surgical intervention.

Major advances have been made in coronary artery stent technology over the last decades. Drug-eluting stents reduced in-stent restenosis and have shown better outcomes compared with bare metal stents, yet some limitations still exist to their use. Because they delay healing of the vessel wall, longer dual antiplatelet therapy is mandatory to mitigate against stent thrombosis and this limitation is most concerning in subjects at high risk for bleeding. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced inflammation and thromboresistance in preclinical studies, suggesting more flexible dual antiplatelet therapy requirement with potential benefits especially in those at high bleeding risk. Here, we discuss the significance of COBRA PzF in light of recent experimental and clinical studies.Coronary artery disease occurs when the inner walls of the coronary arteries thicken due to plaque build-up. As the plaque develops, the inside of the artery narrows, and blood flow to the heart muscle is restricted. Coronary stents act as a miniature circular scaffolding that flexes to fit the shape of the artery. In the COBRA PzF nanocoated coronary stent, Polyzene F nanocoating (PzF) has been applied to the stent’s surface. Experimental studies have shown that PzF nanocoatings promote healing after stent implantation and reduce the attachment of platelets and inflammatory cells. The principal safety and effectiveness for the COBRA PzF stent has been proven by clinical studies, showing that the COBRA PzF stent was as safe and effective as other approved bare metal coronary stents. Here, we summarize the findings of experimental and clinical studies with the COBRA PzF stent and discuss potential future directions of anti-platelet and anti-coagulant medications following COBRA PzF stent implantation.

Background Image-guided percutaneous core needle biopsy (CNB) has been an important diagnostic procedure for musculoskeletal lesions. Here we surveyed the variety of diagnostic strategies available and assessed the clinical usefulness and limitations of image-guided CNB carried out by a multidisciplinary team comprising specialists in various fields. Methods We conducted a retrospective study of 284 image-guided CNBs among 1899 consecutive biopsy procedures carried out at our institution for musculoskeletal tumorous conditions, focusing on their effectiveness including diagnostic accuracy and utility for classification of specimens according to malignant potential and histological subtype as well as their correlation with biopsy routes. Results Among the 284 studied biopsies, 252 (88.7%) were considered clinically “effective”. The sensitivity for detection of malignancy was 94.0% (110/117) and the specificity was 95.3% (41/43). The diagnostic accuracy for detection of malignancy was 94.4% (151/160) and that for histological subtype was 92.3% (48/52). The clinical effectiveness of the procedure was correlated with the complexity of the biopsy route (P = 0.015); the trans-pedicular, trans-retroperitoneal and trans-sciatic foramen approaches tended to yield ineffective results. Repeat biopsy did not have a significant impact on the effectiveness of image-guided CNB (P = 0.536). Conclusions The diagnostic accuracy rates of image-guided CNB performed at multidisciplinary sarcoma units were usable even for patients who have variety of diagnostic biopsy procedures. It is important to establish and implement diagnostic strategies based on an understanding that complicated routes, especially for spine and pelvic lesions, may be associated with ineffectiveness and/or complications.

Hemolytic anemia and pure red cell aplasia are rare hematological complications of hepatitis B virus infection. We herein report a 24-year-old man who was diagnosed with hemolytic anemia and possible transient pure red cell anemia eight weeks after a severe episode of acute hepatitis B virus infection. Rapid recovery was observed with conservative management. Hemoglobin returned to baseline within three months. As the clinical features of hemolytic anemia associated with hepatitis B virus have not yet been elucidated, we conducted a systematic review and present an analysis of the 20 reported cases, including our present case.

Synovial sarcoma is characterized by variable epithelial differentiation and specific SS18-SSX gene fusions. The diagnosis is primarily based on phenotype, but fusion gene detection is increasingly being considered indispensable, with SS18 break-apart fluorescence in situ hybridization (FISH) being favored in many laboratories. However, SS18 FISH assay produces negative or atypical results in a minority of cases, leaving uncertainties in diagnosis and management. Here, we analyzed this challenging subset of SS18 FISH-negative/atypical synovial sarcoma using RNA sequencing and monoclonal antibodies that recognize SS18-SSX and the SSX C-terminus. Among 99 synovial sarcoma cases that were previously subjected to SS18 break-apart FISH, eight cases were reported as negative and three cases were indeterminate, owing to atypical signal patterns. Three of these 11 tumors (two monophasic and one biphasic) harbored novel EWSR1-SSX1 fusions, were negative for SS18-SSX staining, and were positive for SSX C-terminus staining. One monophasic tumor harbored a novel MN1-SSX1 fusion, and showed negative SS18-SSX expression and positive SSX C-terminus staining. Another monophasic tumor carried an SS18L1-SSX1 fusion, and was weakly positive for SS18-SSX, while SMARCB1 expression was reduced. The presence of these novel and/or rare fusions was confirmed using RT-PCR and Sanger sequencing. EWSR1-SSX1 was further validated by EWSR1 FISH assay. The remaining six tumors (five monophasic and one biphasic) showed strong SS18-SSX expression, and RNA sequencing successfully performed in three cases identified canonical SS18-SSX2 fusions. Based on a DNA methylation-based unsupervised clustering, the tumors with EWSR1-SSX1 and SS18L1-SSX1 clustered with synovial sarcoma, while the MN1-SSX1-positive tumor was not co-clustered despite classic histology and immunoprofile. In summary, we discovered novel and rare SSX1 fusions to non-SS18 genes in synovial sarcoma. The expanded genetic landscape carries significant diagnostic implications and advances our understanding of the oncogenic mechanism.

Background and Objective: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. Methods: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior pulmonary veins (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP) and conduction properties within the PVs were analyzed. Results: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI-dependent anisotropic conduction at the AF onset was visualized in a 3D-mapping. Onset of AF was site-specific with reproducibility in each individual. Mean ERP in LSPV in the AF inducible group was shorter than that in the AF non-inducible group (182 ± 55 ms vs 254 ± 51 ms, P

Background/purpose: Dentures are important for the reconstruction of occlusal support and masticatory performance for older adults with poor dentition. We aimed to elucidate the oral health factors associated with malnutrition in older adults requiring long-term care, including denture use. Materials and methods: This cross-sectional study included 322 older adults (63 men, 259 women; mean age, 86.6 ± 6.9 years) who required long-term care in rural Japan. The participant's nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA®-SF). Oral health was assessed using participant's dentition and oral function. Barthel Index (BI) and medical history were measured for assessing general health status. Multiple logistic regression analyses were performed to determine the oral health factors associated with malnutrition. Results: The proportion of participants with malnutrition was 17.2%. The BI score (odds ratio [OR], 0.95; 95% confidence interval [CI] 0.93–0.98, p

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.

Background Spinal disorders and low back pain (LBP) have been associated with worse clinical outcomes of total hip arthroplasty (THA). It is essential to identify spinal factors associated with post-THA LBP improvement. Therefore, we aimed to determine the proportion of patients with improved LBP after THA and to identify the preoperative spinal factors associated with LBP improvement. Methods We included 151 patients who underwent primary THA between December 2015 and December 2019 and had a preoperative visual analog scale score for LBP of ≥2. The patients were classified into the LBP improved or LBP continued group based on a visual analog scale score for LBP at 1 year after THA. Preoperative spinal parameters were compared between the 2 groups. Results Ninety-five patients (62.9%) were classified into the LBP improved group. Among the coronal spinal parameters, the Cobb angle was significantly lower in the LBP improved group. Among the sagittal spinal parameters, the LBP continued group showed a significantly more posteriorly titled pelvis, lower lumbar lordosis, greater sagittal vertical axis, and greater pelvic incidence minus lumbar lordosis mismatch, indicating a sagittal spinal imbalance. Logistic regression analysis found that preoperative factors associated with LBP improvement after THA had a low Cobb angle and high anterior pelvic plane angle (anteriorly tilted pelvis). Conclusion Among patients with LBP before THA, 62.9% had improved LBP. Sagittal spinal imbalance and high Cobb angle were the key spinal factors associated with persistent LBP. Our findings suggest that hip surgeons should evaluate spinal alignment before THA in patients with LBP.

Purpose: Posterior urethral valves (PUVs) are the most common cause of congenital bladder obstruction in boys. Our aim was to assess the impact of early diagnosis and fulguration of PUVs on bladder function and compare their functional and urodynamic outcome with children who underwent delayed intervention. Materials and Methods: We retrospectively evaluated 153 patients who underwent primary valve ablation from two tertiary hospitals between 2001 and 2018. Patients have been divided into 2 groups, group 1 included 69 patients who were detected antenatally and underwent early fulguration of PUVs while group 2 included 84 children presented postnatally and underwent delayed valve ablation. The recorded data throughout follow-up in renal function tests, urodynamics and changes in the upper urinary tracts were evaluated and compared. Results: Median age at time of valve ablation was 10 days in group 1 and 7 months in group 2. The median follow-up period was 6.5 and 7 years in group 1 and 2, respectively. Chronic kidney disease (CKD) developed in 15 (22%) boys in group 1 while in group 2 it was observed in 31 (37%), p=0.04. While Q-max, mean bladder capacity and post-void residual (PVR) volumes were comparable in both groups, percent PVR was significantly higher in group 2 (3.27 vs. 1.44, p=0.002). Detrusor overactivity was slightly different in both groups (p = 0.07). Conclusions: Compared to delayed intervention, primary ablation of PUVs during the early neonatal life possibly provides the optimum chance to have optimum renal function without impact on bladder function.

Background Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients. Methods Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed. Results The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer. Conclusion Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.

The pathogenesis of gonadotropin-independent precocious puberty (PP) includes both congenital and acquired forms, the latter of which may be associated with neoplasms, such as sex-steroid hormone-producing tumors. Beta-human chorionic gonadotropin (β-hCG)-producing tumors also cause gonadotropin-independent PP by stimulating the production of testosterone in Leydig cells. Germ cell tumors and hepatoblastoma both produce β-hCG; however, there is limited evidence to show that gonadotropin-independent PP is caused by other β-hCG-producing tumors. We herein report the first case of β-hCG-producing neuroblastoma associated with the development of gonadotropin-independent PP. A 2-year-old boy presented with an increased penile length, enlargement of the testes, pigmentation of the external genitalia, and growth acceleration. Imaging, blood, and urinary examinations revealed the presence of neuroblastoma in the right adrenal region. Decreased levels of luteinizing hormone and follicle-stimulating hormone with an increased testosterone level were indicative of gonadotropin-independent PP. Since serum β-hCG was elevated, β-hCG-producing neuroblastoma was suspected. Histological findings of the resected tumor were compatible with neuroblastoma. An immunohistochemical analysis using serial sections revealed staining for β-hCG in synaptophysin-positive cells. Furthermore, immunofluorescence showed the co-staining of β-hCG with neuron-specific enolase. These results suggested that β-hCG was produced by tumor cells. Surgical removal of the tumor promptly normalized serum β-hCG and testosterone levels. In conclusion, we propose the addition of neuroblastoma to the list of differential diagnoses of gonadotropin-independent PP with β-hCG positivity in serum that includes germ cell tumors and hepatoblastoma.

An interaction between acute myeloid leukemia (AML) cells and endothelial cells in the bone marrow seems to play a critical role in chemosensitivity on leukemia treatment. The endothelial niche reportedly enhances the paracrine action of the soluble secretory proteins responsible for chemoresistance in a vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR-2) signaling pathway–dependent manner. To further investigate the contribution of VEGF-A/VEGFR-2 signaling to the chemoresistance of AML cells, a biochemical assay system in which the AML cells were cocultured with human endothelial EA.hy926 cells in a monolayer was developed. By coculture with EA.hy926 cells, this study revealed that the AML cells resisted apoptosis induced by the anticancer drug cytarabine. SU4312, a VEGFR-2 inhibitor, attenuated VEGFR-2 phosphorylation and VEGF-A/VEGFR-2 signaling–dependent endothelial cell migration; thus, this inhibitor was observed to block VEGF-A/VEGFR-2 signaling. Interestingly, this inhibitor did not reverse the chemoresistance. When VEGFR-2 was knocked out in EA.hy926 cells using the CRISPR–Cas9 system, the cytarabine-induced apoptosis of AML cells did not significantly change compared with that of wild-type cells. Thus, coculture-induced chemoresistance appears to be independent of VEGF-A/VEGFR-2 signaling. When the transwell, a coculturing device, separated the AML cells from the EA.hy926 cells in a monolayer, the coculture-induced chemoresistance was inhibited. Given that the migration of VEGF-A/VEGFR-2 signaling–dependent endothelial cells is necessary for the endothelial niche formation in the bone marrow, VEGF-A/VEGFR-2 signaling contributes to chemoresistance by mediating the niche formation process, but not to the chemoresistance of AML cells in the niche.

Pulmonary thromboembolism (PTE) is one of the leading causes of maternal mortality. We previously reported that possible contamination of amniotic fluid (AF) into maternal circulation accelerated thrombin production and activated platelet function in maternal blood through the extrinsic pathway, which may be associated with the high incidence of PTE in early puerperium. However, it remains unclear whether the maternal anticoagulation system, e.g., the activated protein C (APC) pathway, contributes to the hypercoagulable condition induced by AF. Our previous study using an endogenous thrombin potential (ETP)-based assay revealed that sensitivity to APC was reduced during the postpartum first day, i.e., immediately after delivery, when parturients were supposed to be exposed to AF. Our aim is to investigate the susceptibility of maternal plasma to APC when mixed with AF. We collected plasma from 51 pregnant females and mixed with AF as well as APC. APC-sensitivity ratio (APC-sr) was calculated using the ETP-based assay. Addition of AF to maternal plasma showed a significant increase of ETP in the presence of APC. APC-sr was significantly increased, indicating decreased sensitivity to APC, after AF mixture to maternal plasma. The present APC-sr difference with AF contamination was smaller than that we reported previously in venous thromboembolism cases. The inhibitory effects of AF on the APC anticoagulation pathway may contribute, at least partly, to further promotion of thrombin production induced by AF. Combined with other classical thrombophilic risk factors, the present findings support possible involvements of AF exposure in the high incidence of PTE in early puerperium.

Key Points Allele-specific methylation of the ASNS gene is associated with asparaginase sensitivity and therapeutic outcome in T-ALL.Pediatric T-ALL patients with poor prognostic SPI1 fusion exclusively exhibited ASNS hypomethylation status., Visual Abstract, Asparaginase therapy is a key component of chemotherapy for patients with T-cell acute lymphoblastic leukemia (T-ALL). Asparaginase depletes serum asparagine by deamination into aspartic acid. Normal hematopoietic cells can survive due to asparagine synthetase (ASNS) activity, whereas leukemia cells are supposed to undergo apoptosis due to silencing of the ASNS gene. Because the ASNS gene has a typical CpG island in its promoter, its methylation status in T-ALL cells may be associated with asparaginase sensitivity. Thus, we investigated the significance of ASNS methylation status in asparaginase sensitivity of T-ALL cell lines and prognosis of childhood T-ALL. Sequencing of bisulfite polymerase chain reaction products using next-generation sequencing technology in 22 T-ALL cell lines revealed a stepwise allele-specific methylation of the ASNS gene, in association with an aberrant methylation of a 7q21 imprinted gene cluster. T-ALL cell lines with ASNS hypermethylation status showed significantly higher in vitro l-asparaginase sensitivity in association with insufficient asparaginase-induced upregulation of ASNS gene expression and lower basal ASNS protein expression. A comprehensive analysis of diagnostic samples from pediatric patients with T-ALL in Japanese cohorts (N = 77) revealed that methylation of the ASNS gene was associated with an aberrant methylation of the 7q21 imprinted gene cluster. In pediatric T-ALL patients in Japanese cohorts (n = 75), ASNS hypomethylation status was significantly associated with poor therapeutic outcome, and all cases with poor prognostic SPI1 fusion exclusively exhibited ASNS hypomethylation status. These observations show that ASNS hypomethylation status is associated with asparaginase resistance and is a poor prognostic biomarker in childhood T-ALL.

Introduction Immunoglobulin G4-related disease embraces a wide range of extra-pancreatic manifestations. However, localized pathogenesis in gonadal glands, including testes or seminal vesicles, is rare. The clinical course and therapeutic strategy for this disease have not been clearly characterized. Case presentation A 61-year-old Asian male had a left orchiectomy and right seminal vesicle biopsy because of a mass in the left testis and right seminal vesicle. Histological findings showed an infiltration of immunoglobulin G4-positive plasma cells in the respective tissues and met immunoglobulin G4-related disease diagnostic criteria. No recurrence and exacerbation have been observed after 12 years' follow-up without any clinical intervention. To date, immunoglobulin G4-related disease in gonadal tissue is rare. This is the first case with mass-forming lesions in both the testis and seminal vesicle. Conclusion Based on the clinical course of our case and the literature, for patients with accurately diagnosed inactive gonadal immunoglobulin G4-related disease, watchful waiting is a feasible clinical treatment option.

Purpose: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss. Methods: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing. In those Usher patients with repeated measures, regression analysis was done to evaluate for change in visual acuity and dark-adapted threshold with age. Spherical equivalent and full-field electroretinogram responses from dark- and light-adapted eyes were evaluated as a function of age. Results: The majority of initial visual acuity and spherical equivalent results were within normal limits for age. Visual acuity and dark-adapted threshold worsened significantly with age in Usher type 1 but not in Usher type 2. At initial test, full-field electroretinogram responses from dark- and light-adapted eyes were abnormal in 53% of patients. Remarkably, nearly half of our patients (17% of Usher type 1 and 30% of Usher type 2) would have been missed by tests of retinal function alone if evaluated before age 10. Conclusions: Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone. Thus, genetic testing is needed to secure a diagnosis of Usher syndrome.

Introduction Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1). Methods Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed. Results Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group. Conclusions We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

Background Not every elderly person is frail, and whether it would be beneficial to perform endovascular aneurysm repair (EVAR) solely because a patient is older is unclear. This study aimed to compare the results of EVAR and open surgical repair (OSR) in elderly individuals.Methods and Results:From May 1998 to March 2021, 828 EVAR patients and 886 OSR patients with abdominal aortic aneurysm (AAA) were reviewed. Patients aged ≥80 years were included among them. After propensity score matching by age, sex, and American Society of Anesthesiologists (ASA) classification, the outcomes were compared between patients who underwent EVAR and OSR. The study cohort was composed of 351 EVAR patients and 90 OSR patients. The groups had similar comorbidities, except that EVAR patients were significantly older and had higher ASA classifications. After propensity score matching, 79 pairs of patients were selected. The 30-day mortality (0 vs. 1.2%) and aneurysm-related death (ARD) rates during follow up (2.3% vs. 2.3%, respectively) were similar between the groups. Kaplan-Meier curves revealed that estimated overall survival and freedom from ARD were also similar. Conclusions This study suggests that EVAR cannot improve survival outcomes compared with OSR if applied solely because a patient is aged ≥80 years. Not only age but also other risk factors and quality of life after surgery need to be further studied.

Introduction Boron neutron capture therapy (BNCT) is a biologically targeted, cell-selective particle irradiation therapy that utilizes the nuclear capture reaction of boron and neutron. Recently, accelerator neutron generators have been used in clinical settings, and expectations for developing new boron compounds are growing. Methods and Results In this study, we focused on serum albumin, a well-known drug delivery system, and developed maleimide-functionalized closo-dodecaborate albumin conjugate (MID-AC) as a boron carrying system for BNCT. Our biodistribution experiment involved F98 glioma-bearing rat brain tumor models systemically administered with MID-AC and demonstrated accumulation and long retention of boron. Our BNCT study with MID-AC observed statistically significant prolongation of the survival rate compared to the control groups, with results comparable to BNCT study with boronophenylalanine (BPA) which is the standard use of in clinical settings. Each median survival time was as follows: untreated control group; 24.5 days, neutron-irradiated control group; 24.5 days, neutron irradiation following 2.5 h after termination of intravenous administration (i.v.) of BPA; 31.5 days, and neutron irradiation following 2.5 or 24 h after termination of i.v. of MID-AC; 33.5 or 33.0 days, respectively. The biological effectiveness factor of MID-AC for F98 rat glioma was estimated based on these survival times and found to be higher to 12. This tendency was confirmed in BNCT 24 h after MID-AC administration. Conclusion MID-AC induces an efficient boron neutron capture reaction because the albumin contained in MID-AC is retained in the tumor and has a considerable potential to become an effective delivery system for BNCT in treating high-grade gliomas.

We investigated whether or not computed tomographic colonography (CTC) is a viable alternative to double-contrast barium enema (BE) for a preoperative rectal cancer evaluation. The size and distance from the anal canal to the lower or upper tumor borders were laterally measured in 147 patients who underwent CTC and BE. Measurements were grouped into early cancer, advanced, and after chemoradiation therapy (CRT). In the early and advanced cancer groups, all lesions were visualized by BE. In contrast, 3 (7.8%) early and 8 (7.3%) advanced cases, located at the anterior wall near the anal canal, were not visualized by CTC because of liquid level formation. In the CRT group, 16 (23.5%) and 4 (5.8%) cases were not visualized by CTC and BE, respectively. The BE and CTC size measurements were similar among cohorts. However, the distance from the anal canal's superior margin tended to be longer with BE, especially in early cancer. The differences in distance from the anal canal were significantly larger in the early cancer group than in the other two groups (p = 0.0024). CTC may be a viable alternative imaging modality in some cases. However, BE should be employed in anterior wall cases near the anal canal and CRT cases.

Background Uninterrupted dabigatran during atrial fibrillation (AF) ablation is now established as the standard therapy. However, there are few reports on the effects of uninterrupted dabigatran on the intensity of anticoagulation during AF ablation. Methods We retrospectively analyzed 247 consecutive patients who underwent AF ablation in our hospital from January 2017 to December 2018. Patients who took warfarin or uninterrupted direct oral anticoagulants (DOACs) except for dabigatran were excluded. 89 patients underwent ablation with uninterrupted dabigatran (uninterrupted group, male 71, mean age 59.6 ± 14.0) and 124 with interrupted DOACs (interrupted group, male 105, mean age 56.9 ± 12.9) during AF ablation. The initial ACT level, proportion of ACT levels of more than 300 s, and total amount of heparin were compared. Furthermore, the incidence of procedure complications was also evaluated. Results The initial ACT levels were significantly higher in the uninterrupted group, and the total number of ACTs of more than 300 s was significantly higher in the uninterrupted group (uninterrupted vs. interrupted; initial ACT level, 315.6 ± 59.8 vs. 264.5 ± 48.6, p

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of mesenchymal tumors that arise from the sheath of peripheral nerves. MPNSTs exhibit strong metastatic potential, leading to poor clinical outcomes. The clinical utility of radiation therapy and chemotherapy is marginal with respect to overall survival and effective systematic therapies for MPNSTs are still needed to improve patient outcome. Although patient-derived cell lines are an essential tool for the development of novel therapies, only a limited number of cell lines have been reported and are available from cell banks. Thus, we established the novel MPNST cell line, NCC-MPNST6-C1, using surgically resected MPNST tissue. The NCC-MPNST6-C1 cells retained copy-number alterations similar to those of the original tumors and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro, which reflected the malignant features of the original tumor tissue. While the NCC-MPNST6-C1 cells did not exhibit tumorigenesis in nude mice, their use in drug screening resulted in anti-cancer agents with low IC50 values. Hence, we conclude that the NCC-MPNST6-C1 cell line is a useful resource for the study of MPNSTs.

This study aimed to investigate the effect of sarcopenia on the prognosis of advanced lower rectal cancer patients receiving neoadjuvant chemoradiotherapy (CRT). Sarcopenia has been recognized as an adverse factor for surgical outcomes in several malignancies. However, the impact of preoperative sarcopenia on rectal cancer patients receiving CRT is still unknown. This retrospective study included cT3-T4 anyN M0 lower rectal cancer patients who underwent CRT followed by R0 resection at our institution between October 2003 and December 2016. CRT consisted of 5-fluorouracil-based oral chemotherapy and long course radiation (50.4 Gy/28 fr). The psoas muscle area at the third lumbar vertebra level was evaluated by computed tomography before and after CRT, and was adjusted by the square of the height to obtain the psoas muscle mass index (PMI). Sarcopenia was defined as the sex-specific lowest quartile of the PMI. We assessed the association between pre- and post-CRT sarcopenia and postoperative prognosis. Among 234 patients, 55 and 179 patients were categorized as sarcopenia and non-sarcopenia patients, respectively. Although post-CRT sarcopenia correlated with residual tumor size, it had no association with other pathological features. The median follow-up period was 72.9 months, and the 5-year DFS and OS were 67.0% and 85.8%, respectively. Multivariate analysis showed that post-CRT sarcopenia was independently associated with poor DFS (HR: 1.76; P = 0.036), OS (HR: 2.01; P = 0.049), and recurrence in the liver (HR: 3.01; P = 0.025). Sarcopenia is a poor prognostic indicator in lower advanced rectal cancer patients treated with CRT.

Introduction: There are little data concerning the long-term outcome of single-incision laparoscopic surgery (SILS) for colon cancer. Therefore, we investigated not only the short-term outcomes but also the long-term outcomes of SILS for right-side colon cancer. Methods: We retrospectively compared short- and long-term outcomes of SILS and conventional laparoscopic surgery (CLS) for right-sided colon cancer in our institution. Intergroup differences of short-term outcomes were evaluated using χ2 or Fisher exact tests and 2-sample Student t tests. The disease-free survival rates (long-term outcome) of stage II and III patients were estimated using the Kaplan-Meier method and compared using log-rank tests. Results: There were 290 operations conducted for right-side (cecum and ascending) colorectal cancers from April 2011 to July 2018. Open surgery was performed in 12 cases from start to the operation. SILS was performed in 196 cases and CLS in 55 cases. One patient underwent intraoperative conversion from SILS to laparotomy for bleeding control. In addition, 1 port was added to SILS in 3 cases. These 4 cases were included in the analysis as the SILS group according to the principle of intent to treat. Background: Factors including age, gender, body mass index, performance status, and tumor stage were not statistically different between the SILS and CLS groups. In short-term outcomes, the number of harvested lymph nodes was not statistically different. SILS required less operating time (p < 0.001) and resulted in a reduced bleeding volume (p < 0.001). There was no statistical difference in the frequency of overall complications (p = 0.06). The disease-free survival of stage II and III patients was not statistically different between the 2 groups. Conclusions: With the proper adaptation of SILS by an experienced surgeon, the short- and long-term outcomes of SILS were not inferior to those of CLS. Therefore, SILS could be a treatment option for right-sided colon cancer.

Background Peritoneal dialysis (PD)-associated peritonitis caused by Sphingomonas paucimobilis (S. paucimobilis) is very rare, and most of the characteristics of such cases are still unknown. Case presentation An 80-year-old Japanese woman on PD was diagnosed with PD-associated peritonitis and received ceftazidime and cefazolin. The number of cells in the peritoneal dialysate decreased quickly. However, because S. paucimobilis was detected, the antibiotic was changed to meropenem according to the susceptibility test results. She was treated with meropenem for two weeks and discharged. After 21 days, she was hospitalized for relapsing peritonitis. S. paucimobilis was detected again, and improvement after the administration of meropenem was poor, eventually resulting in catheter removal. Conclusions S. paucimobilis may be resistant to empirical antibiotics; furthermore, catheter removal may still be required, even with sensitive-antibiotic treatment.

Aims Little is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization. Methods and results We analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all‐cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age

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.

Objective Cryosurgery is a simple and effective method for treating oral lesions. In this study, cryosurgery was used for vascular lesions such as haemangioma or vascular malformation and the effect was evaluated clinically. Methods The subjects were patients with a clinical diagnosis of vascular lesions in the oral cavity and who chose cryosurgery after an explanation of both surgical excision and cryosurgery. Cryosurgery was performed with a freezing device using liquid nitrogen. No anaesthesia was administered without the patient's wishes. Results Thirteen patients chose cryosurgery. No serious adverse events occurred during or after cryosurgery. In seven cases, the lesions disappeared after cryosurgery alone. Five cases showed reductions in the size of the lesions with several treatment sessions. One case later underwent surgical excision because cryosurgery was not successful. The results of the analysis showed that complete disappearance tended to be difficult and was dependent on the size of the lesion and the length of time it was left untreated. Conclusions This study suggests that cryosurgery is effective, minimally invasive, and safe treatment for vascular lesions in the oral cavity.

Background Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats. Methods Fifty-one male Sprague–Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed. Results mPAP [35.1 ± 1.7 mmHg (MCT) (n = 9) vs. 16.6 ± 0.7 (control) (n = 9) (P P P P P P Conclusions We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.

Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.5-4.4 years. It was significantly effective in two patients and did not cause serious side effects in any patient. Vedolizumab might be effective and safe for pediatric GI-aGVHD refractory to other treatments, but this must be confirmed in future studies.

Background/purpose: Surgical orthodontic treatment is recommended for patients with severe dentoskeletal discrepancies, while camouflage orthodontic treatment is recommended for patients with mild to moderate discrepancies. However, the decision as to which treatment should be chosen is complicated. The purpose of this study was to determine differences in masticatory function in patients who underwent camouflage and surgical orthodontic treatment for skeletal Class III malocclusion, as well as the usefulness of Wits appraisal in treatment decision based on masticatory functional analysis. Materials and methods: The study subjects were 45 patients with skeletal Class III malocclusion (15 cases with camouflage orthodontics and 30 cases with orthognatic surgery) and 12 individuals with normal occlusion. We analyzed the pre-treatment records of electromyographic activities of masseter and temporalis muscles and jaw movements. Results: There were no significant differences in various functional measurements between the camouflage and surgery groups. However, there were significant but not strong correlations between ANB and both masseter muscle activity (r = 0.36, p < 0.01) and expression ratio of abnormal chewing (r = −0.54, p < 0.01). Division of patients into two groups using a cutoff value of −6.0 mm for Wits appraisal showed a significant difference in masseter muscle activity between −6.0 mm or less group and the control (p < 0.01) but none between more than −6.0 mm group and the control. Conclusion: Camouflage orthodontic treatment is inappropriate for patients with relatively severe dentoskeletal discrepancies. Wits appraisal of −6.0 mm is a potentially useful parameter for treatment decision.

Background The causes of idiopathic ileocolic intussusception are unknown, with infection as the most likely culprit. Recently, social distancing measures were implemented during the coronavirus disease 2019 (COVID-19) pandemic to decrease transmissible infectious diseases, creating an opportune setting to study the role of infection on the pathogenesis of intussusception on a population level. Objective To investigate the impact of social distancing on intussusception. Materials and methods We retrospectively reviewed air contrast enemas and pylorus ultrasounds performed between March 2010 and March 2021 to identify cases of ileocolic intussusception and hypertrophic pyloric stenosis (HPS), using the latter as a negative control. The study time frame was divided into two periods: pre-pandemic (March 2010–February 2020) and pandemic (April 2020–March 2021). The number of cases that occurred in these two time periods were compared using the Poisson regression model. Results Of the 407 cases of idiopathic ileocolic intussusception identified, 396 occurred in the pre-pandemic time period (mean = 39.6 per 12-month period) and 11 occurred in the 12-month pandemic time period. The mean monthly number of intussusceptions showed a decline of 72% (95% confidence interval [CI] 49–85%) between the pre-pandemic and pandemic time periods (3.3 vs. 0.9 monthly cases; P

Aims To compare endoscopy gastric cancer images diagnosis rate between artificial intelligence (AI) and expert endoscopists. Patients and methods We used the retrospective data of 500 patients, including 100 with gastric cancer, matched 1:1 to diagnosis by AI or expert endoscopists. We retrospectively evaluated the noninferiority (prespecified margin 5 %) of the per-patient rate of gastric cancer diagnosis by AI and compared the per-image rate of gastric cancer diagnosis. Results Gastric cancer was diagnosed in 49 of 49 patients (100 %) in the AI group and 48 of 51 patients (94.12 %) in the expert endoscopist group (difference 5.88, 95 % confidence interval: −0.58 to 12.3). The per-image rate of gastric cancer diagnosis was higher in the AI group (99.87 %, 747 /748 images) than in the expert endoscopist group (88.17 %, 693 /786 images) (difference 11.7 %). Conclusions Noninferiority of the rate of gastric cancer diagnosis by AI was demonstrated but superiority was not demonstrated.

OBJECTIVE Although anterior compression factors and cervical alignment affect neural decompression, cervical laminoplasty may be used to achieve indirect posterior decompression. The focal apex (FA) angle of the anterior compression factor of the spine represents the degree of anterior prominence toward the spinal cord. The authors investigated the mechanism underlying the influence of FA angle and cervical alignment on spinal cord alignment (SCA) after laminoplasty, including how high-intensity signal cord change (HISCC) on preoperative T2-weighted MRI (T2-MRI) may affect neurological improvement. METHODS We performed a retrospective study of patients who underwent laminoplasty for CSM or OPLL at two hospitals (Kanto Rosai Hospital, Kawasaki City, and Yokohama Minami Kyousai Hospital, Yokohama City, Japan) between April 2004 and March 2015. In total, 109 patients (mean age 67.3 years) with cervical compression myelopathy were included. FA angle was defined as the preoperative angle between the lines from the top of the prominence to the upper and lower adjacent vertebrae. Preoperative cervical alignment was measured between the C2 and C7 vertebrae (C2–7 angle). MRI was used to classify SCA as lordosis (type-L SCA), straight (type-S), local kyphosis (type-LK), or kyphosis (type-K). Preoperative HISCC was investigated by using T2-MRI. Neurological status was evaluated by using the Japanese Orthopaedic Association score. RESULTS The mean preoperative FA and C2–7 angles were 32.1° and 12.4°, respectively. Preoperative SCA was type-L or type-S in 53 patients. The neurological recovery rate (NRR) was significantly higher for patients with preoperative type-L and type-S SCA (51.4% for those with type-L and 45.0% for those with type-S) than for patients with other types (35.3% for those with type-LK and 31.7% for those with type-K). Among patients with preoperative type-L or type-S SCA, 87.3% maintained SCA; however, 5/12 (41.7%) patients with a preoperative average C2–7 angle < 12.4° and an average FA angle > 32.1° had postoperative type-LK or type-K SCA. SCA changed to type-L or type-S in 13.0% of patients with preoperative type-LK or type-K SCA. Moreover, in these patients, FA angle was significantly smaller and NRR was significantly higher than in other patients in whom postoperative SCA remained type-LK or type-K. Preoperative T2-MRI showed 73 patients with HISCC (43 with type-L and type-S, and 30 with type-LK and type-K SCA) and 36 without HISCC (20 with type-L and type-S, and 16 with type-LK and type-K SCA); the NRRs of these patients were 42.6% and 41.2%, respectively. No significant differences in SCA or NRR were observed between patients with and without HISCC. CONCLUSIONS NRR depends on preoperative SCA type; however, it is possible to change the type of SCA after laminoplasty. Preoperative FA and C2–7 angles influence change in SCA; therefore, they are important parameters for successful decompression with cervical laminoplasty.

A 64-year-old man presented with epigastric pain and underwent contrast-enhanced computed tomography. Ruptured aneurysm of the inferior pancreaticoduodenal artery was diagnosed. TAE was successfully accomplished using coils, but vomiting appeared 9 days later. Duodenal stenosis was diagnosed from contrast-enhanced computed tomography and upper gastrointestinal endoscopy and was attributed to edematous changes in the duodenum. Conservative management led to successful recovery and discharge.

To determine risk factors associated with concussion among the general collegiate population using a unique data linkage methodology.Student health medical, counseling, and disability access service data were linked with university enrollment data to provide a comprehensive, deidentified dataset of students who sought care at the student health center for concussion from 2016-2020. Using chi-squared tests and logistic regression, characteristics of students with and without concussion were evaluated.During the study period, 506 concussions from 474 students were identified (cumulative incidence rate of 51.7 per 10,000 students). Significant predictors of concussion included: younger age (21 years): odds ratio (OR) = 3.52 (95% confidence intervals [CI], 2.78, 4.50), Greek affiliation: OR = 1.89 (95% CI, 1.56, 2.30), and utilization of counseling and psychological services: OR = 1.92 (95% CI 1.59, 2.32). Of the students with concussion, 47% had at least one other concussion within the preceding year. History of prior hospitalization or medical imaging for head injury increased subsequent concussion risk by 4.5 fold.Linking unique datasets provides a richer understanding of the characteristics and risk factors associated with student concussions than analysis of a single data source. This comprehensive dataset will enable future targeted interventions to prevent and treat college student concussions.

Primary malignant pericardial mesothelioma is an extremely rare disease. Malignant disease of the pericardium is an infrequent cause of cardiac tamponade. Hence, cardiac tamponade in the context of primary malignant mesothelioma of the pericardium is an uncommon clinical scenario. A 67-year-old male patient, an ex-smoker, complaining of progressive lethargy was referred to a hospital for investigation of persistent pericardial effusion. The pericardial fluid cytology was categorized as class Ⅲ. Thereafter, he was referred to our hospital for further evaluation. Fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed FDG accumulation in the pericardium and mediastinal lymph node. Surgical biopsy of the pericardium was performed through a subxiphoid approach for a definitive diagnosis. Histopathological examination revealed diffuse infiltration of the pericardium by a malignant tumor consisting of epithelioid cells with large round nuclei and prominent nucleoli, arranged in a tubular papillary pattern. Finally, the patient was diagnosed with primary malignant pericardial mesothelioma of epithelioid type. The patient died 6 weeks after admission. This diagnosis must be considered in patients having unexplained massive pericardial effusion. Furthermore, we should consider prompt cytological analysis and FDG PET to arrive rapidly at a definitive diagnosis to administer combination chemotherapy that may provide clinical benefit.

Objective To evaluate the health-related quality of life (QOL) of testicular cancer (TC) survivors using the Japanese version of the EORTC QLQ-TC26 questionnaire in a multi-institutional, cross-sectional study. Methods This study recruited TC survivors who were followed after treatment for TC at eight high-volume institutions between January, 2018 and March, 2019. The participants completed the EORTC QLQ-TC26 questionnaire and mailed the completed questionnaires to a central institution. The QOL scores were assessed according to therapeutic modality (watchful waiting, WW; chemotherapy, CT; and CT followed by retroperitoneal lymph node dissection, CT+RPLND) and follow-up period and compared using analysis of variance and Student's t-test. Results A total of 567 TC survivors responded to the questionnaire. The median age at response was 43 years (IQR 35-51 years), and the median follow-up was 5.2 years (IQR 2.2-10.0 years). As for treatment side effects and physical limitations, the scores of the CT+RPLND group were significantly higher than those of the WW group, especially within one year after treatment. In addition, TC survivors in the CT+RPLND group reported high impairment related to job and education problems and future perspective less than 5 years after treatment. Even TC survivors in the WW group were anxious about job and education issues within one year after treatment. Conclusion TC survivors were anxious about not only cancer recurrence, but also their jobs and education. TC patients should be given appropriate information on QOL after treatment for TC to attenuate post-treatment anxiety and improve their health-related QOL.