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We report a rare case of intravascular large B-cell lymphoma (IVLBCL) with hypopituitarism and respiratory failure. A man in his 80s presented with hypotension and respiratory failure but was unsuccessfully treated for septic shock. Biological investigations were performed, and he was diagnosed with hypopituitarism due to insufficient secretion of anterior pituitary hormone. Although his condition temporarily improved following hormone replacement therapy, he eventually died of progressive respiratory failure. The lymphoma was only discovered during the autopsy, where it was observed to have spread to the pituitary gland and lung capillaries. Therefore, we concluded that the lymphoma had caused respiratory failure and hypopituitarism. The patient was thus diagnosed with IVLBCL posthumously. In conclusion, IVLBCL can cause hypopituitarism and respiratory failure due to pituitary and pulmonary capillary invasion by lymphoma cells.

AIM No flow-limiting dissection after drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions is considered as one of the endpoints, but it has not investigated the difference between each vessel dissection. This study aimed to clarify whether there is a difference between no dissection and type C dissection without flow-limiting dissection for 3 months by peak systolic velocity ratio (PSVR) based on duplex ultrasonography. METHODS Between February 2020 and April 2021, 44 consecutive de novo FP diseases that underwent endovascular therapy (EVT) with DCB were enrolled in this study. 65.9% of the patients had intermittent claudication, and mean lesion lengths were 194±107 mm. The chronic total occlusion was 38.6%. After DCB treatment, vessel dissection pattern was categorized by angiography. The minimum lumen area (MLA) identified by intravascular ultrasound was serially evaluated with PSVRs at 1 day, 1 month, and 3 months after EVT. RESULT All lesions were treated with DCB without provisional stents. The vessel dissection pattern after DCB treatment showed that types D, E, and F were not observed, 9% were no dissection, 27% were type A, 32% were type B, and 32% were type C. In all cases, the PSVR values of MLA site were less than 2.6 at 3 months, and there were no significant differences between no dissection and type C dissection. CONCLUSION Up to dissection pattern "C" is considered acceptable as one of the endpoints to determine the need for provisional stenting after DCB treatment.

Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy.We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68 ± 11 years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1 year after percutaneous coronary intervention (PCI). The stents (n = 106) were divided into three groups according to the lesion status at the previous PCI: CTO (n = 17), acute coronary syndrome (ACS) (n = 35), and stable coronary artery disease without CTO or non-CTO (n = 54).The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4 ± 0.5, 0.9 ± 0.8, and 1.4 ± 0.8, respectively, p 0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71 %, 51 %, and 15 %, respectively, p 0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5 ± 0.7, 1.4 ± 0.6, and 0.9 ± 0.7, respectively, p = 0.007).Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.

The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

Hypertrophic pachymeningitis (HP) is a rare disorder that causes localized or diffuse inflammatory fibrosis and thickening of the dura mater. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related HP is the most frequent form of HP. Otitis media with AAV (OMAAV) patients with HP are associated with higher rates of both ANCA-negative phenotypes and disease-related mortality. However, few studies have reported the imaging characteristics of HP due to AAV/OMAAV. Therefore, we investigated this issue in the present study.This retrospective study included patients diagnosed with HP between 2011 and 2020 at our hospital. Age, sex, causative disease, serum C-reactive protein (CRP) level, and MRI data were collected from medical records. We compared the locations of MRI enhancement depending on the causative diseases.Of the 18 included patients with HP (mean age, 64.1 ± 2.6 years; range, 33-77 years), 10 (55.6%) were female, 12 (66.7%) were diagnosed with AAV/OMAAV, four (22.2%) were diagnosed as idiopathic, two (11.1%) were diagnosed with invasive Aspergillus mastoiditis. Eleven (61.1%) had cranial neuropathies. Facial nerve paralysis was common in AAV/OMAAV, while abducent nerve paralysis was common in idiopathic HP. Cranial fossa enhancement was most common presentation in patients with HP, whereas inner acoustic canal (IAC) enhancement was seen only in patients with AAV/OMAAV, while HP involving the cavernous sinus was seen only in patients with idiopathic and mastoiditis.HP involving the IAC may be a key factor in diagnosing AAV/OMAAV.

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.

A novel bladder preservation therapy, the OMC (Osaka Medical College) regimen, which combines radiation therapy with balloon-occluded arterial infusion of anticancer agents, is a treatment option for patients with muscle-invasive bladder cancer (MIBC). We retrospectively analysed the effects of changes in radiation dose and irradiation field on treatment efficacy and adverse events.The purpose of this study is to use the results of this study to help determine a course of radiation therapy for bladder preservation therapy of cT2N0M0 MIBC.We examined 352 patients with clinical stage T2N0M0 (cT2N0M0) MIBC classified into the following groups based on the irradiation method: group A, the whole pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group B, the small pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group C, the whole pelvis (40 Gy/20 fractions) + local bladder (10 Gy/5 fractions).The complete response rate, 3-year overall survival and progression-free survival rates in group A were 92.9%, 94.9% and 82.1%, respectively; in group B were 87.2%, 86.7% and 76.7%, respectively; and in group C were 95.2%, 92.6% and 71.1%, respectively. No significant differences between the groups were noted. The incidence of ≥grade 3 urinary tract and gastrointestinal toxicities were not significantly different among the groups (group A: 7.8%, 1.7%; B, 11.1%, 0%; C, 7.1%, 1.8%, respectively). The 3-year progression-free rates of the common iliac lymph node (CILN) region in patients who received whole-pelvis and small-pelvis irradiation were 99.0 and 89.0% (P0.01), respectively, with the latter group having significantly high lymph node recurrence in the CILN region.Our findings showed that the optimal radiation therapy for patients with cT2N0M0 MIBC undergoing the OMC regimen is whole-pelvis irradiation including the CILN region, with a total dose of 50 Gy/25 fractions.

Magnetoencephalography (MEG) is a useful tool for clinically evaluating the localization of interictal spikes. Neurophysiologists visually identify spikes from the MEG waveforms and estimate the equivalent current dipoles (ECD). However, presently, these analyses are manually performed by neurophysiologists and are time-consuming. Another problem is that spike identification from MEG waveforms largely depends on neurophysiologists' skills and experiences. These problems cause poor cost-effectiveness in clinical MEG examination. To overcome these problems, we fully automated spike identification and ECD estimation using a deep learning approach fully automated AI-based MEG interictal epileptiform discharge identification and ECD estimation (FAMED). We applied a semantic segmentation method, which is an image processing technique, to identify the appropriate times between spike onset and peak and to select appropriate sensors for ECD estimation. FAMED was trained and evaluated using clinical MEG data acquired from 375 patients. FAMED training was performed in two stages: in the first stage, a classification network was learned, and in the second stage, a segmentation network that extended the classification network was learned. The classification network had a mean AUC of 0.9868 (10-fold patient-wise cross-validation); the sensitivity and specificity were 0.7952 and 0.9971, respectively. The median distance between the ECDs estimated by the neurophysiologists and those using FAMED was 0.63 cm. Thus, the performance of FAMED is comparable to that of neurophysiologists, and it can contribute to the efficiency and consistency of MEG ECD analysis.

Lead (Pb) exposure has adverse health effects and altered DNA methylation may contribute to Pb toxicity. LINE-1 is an interspersed repeated DNA that is used as a surrogate marker for estimating genomic DNA methylation levels, and GSTP1 is an isozyme that detoxifies xenobiotics like Pb, and its expression is inhibited by methylation. Thus, to assess the effects of Pb exposure on global hypomethylation and gene-specific promoter hypermethylation, we examined DNA methylation at LINE-1 repetitive elements and the GSTP1 promoter region. Blood samples were obtained from children (N = 123) living in Pb-polluted areas (as exposed children) and children (N = 63) living in Pb-unpolluted areas (as control children) in Kabwe, Zambia. ICP-MS was used to determine blood lead levels (BLLs), and pyrosequencing and a fluorescence-based polymerase chain reaction assay were used to determine levels of LINE-1 methylation and GSTP1 promoter methylation, respectively. Inverse association was found between BLLs and LINE-1 methylation (β = - 0.046

Purpose Hepatobiliary scintigraphy is a minimally invasive imaging method that evaluates bile flow dynamics. At our hospital, it has been performed for postoperative evaluation of patients with choledochal cysts (CC). This study evaluated the usefulness of biliary scintigraphy for predicting late complications in patients with CCs. Methods The study included pediatric patients with CC who underwent surgery at Chiba University Hospital from 1978 to 2020, followed by postoperative biliary scintigraphy and subsequent radiologic evaluation. The patients were divided into two groups according to the presence or absence of “biliary cholestasis” on biliary scintigraphy. Results The study included 108 patients, with a median age at surgery of 2 years and 11 months. The median follow-up period was 5203 days, with 11 hepatolithiasis cases and 8 cholangitis cases. No patients had cholangiocarcinoma. Twelve patients were considered to have “cholestasis” following biliary scintigraphy evaluation. There was no significant difference in the occurrence of hepatolithiasis between the cholestasis and non-cholestasis groups (p = 0.47), but cholangitis was significantly more common in the cholestasis group (p = 0.016). Conclusion Biliary cholestasis on postoperative hepatobiliary scintigraphy was a risk factor for cholangitis in patients with CCs. These particular patients should be monitored carefully.

To investigate the differences in amniotic fluid cardiac biomarkers and clinical features among types of right ventricular outflow tract (RVOT) abnormality in monochorionic (MC) twins.This prospective study included MC twins that underwent laser surgery. Recipient or larger twins (group A) and donor or smaller twins (group B) were assessed and divided into those with a normal right ventricular outflow tract (normal RVOT), functional pulmonary atresia (fPA), or pulmonary stenosis (PS). Amniotic fluid levels of NT-proBNP (afNT-proBNP) and cardiac troponin T (afTnT) were examined during surgery.Of 190 fetuses in group A, there were 14 RVOT abnormality cases (including 7 fPA and 7 PS). No group B fetuses showed RVOT abnormality findings. In group A, later and earlier gestational age at surgery were observed in fPA (25.1 ± 2.8 weeks) and PS groups (17.8 ± 0.9 weeks). All survived PS cases demonstrated progressive pulmonary valve obstruction, not observed in fPA groups. AfNT-proBNP were significantly higher in fPA and PS than in the normal RVOT group (p 0.05). AfTnT was significantly higher in group A with PS than fPA and normal RVOT groups (p 0.05).Among RVOT abnormality types in group A, amniotic fluid cardiac biomarkers were differently expressed, and clinical features were also differentiated. These findings provide insight into the pathophysiological influence on RVOT in MC twins.This study was registered with the Japanese Clinical Trial Registry "UMIN-CTR" (http://www.umin.ac.jp/ctr/index-j.htm; trial ID numbers UMIN000024486 and 000037702).

The ground reaction force (GRF) is known to produce tibial internal rotation loading associated with the stress in the anterior cruciate ligament (ACL). However, it is unclear whether the friction moment (FM; the moment due to horizontal shoe-floor friction, acting around the vertical axis at the GRF acting point) facilitates or restrains the effect of GRF-driven tibial rotation loading during cutting. The 45° cutting motions with forefoot/rearfoot strikes were captured simultaneously with GRF and FM data from 23 healthy males. The FM- and GRF-driven tibial rotation moments were calculated. Time-series correlation between FM- and GRF-driven tibial rotation moments and the orientation relationship among those moment vectors was investigated. The FM-driven tibial rotation moment negatively correlated with the GRF-driven one within the first 10% of stance phase. The peak regression slope value was -0.34 [SD 0.33] for forefoot and -1.64 [SD 1.76] for rearfoot strikes, showing significant difference from zero (SPM one-sample t-test, p0.05). The FM-driven tibial "external" rotation moment counteracted the GRF-driven tibial "internal" rotation moment within first 10% of the stance phase in most trials, suggesting that the FM-driven tibial rotation moment potentially diminishes the effect of GRF-driven one and may reduce ACL injury risk during cutting.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.

γ-Glutamylcyclotransferase (GGCT) is up-regulated in a broad range of cancers, including breast cancer, and GGCT inhibition has been shown to be a promising strategy for therapy. Herein, we evaluated the efficacy and mechanism of action of pro-GA, a GGCT enzymatic inhibitor, in MCF7 breast cancer cells.Proliferation was evaluated by WST-8 and trypan blue dye exclusion assays. Western blot analysis was conducted to examine the expression of cyclin-dependent kinase inhibitors (CDKI), including p21, p27, and p16. Induction of senescence was assessed by senescence-associated β-galactosidase staining. Generation of mitochondrial superoxide reactive oxygen species (ROS) was assessed using flow cytometry. The effect of N-acetylcysteine (NAC) on pro-GA dependent inhibition of proliferation, ROS generation, and senescence was also studied. The efficacy of systemic administration of pro-GA was evaluated in a MCF7 xenograft mouse model.Treatment with pro-GA inhibited proliferation of MCF7 cells, increased CDKI expression and mitochondrial ROS, and induced cellular senescence. We found that cotreatment with NAC restored proliferation in pro-GA treated cells. NAC similarly suppressed CDKI expression, mitochondrial ROS generation, and senescence induced by pro-GA. Furthermore, the systemic administration of pro-GA in an MCF7 xenograft model had significant antitumor effects without toxicity.Pro-GA may be a promising therapeutic agent for the treatment of breast cancer.

Mitral valve surgery employing a superior transseptal approach (STA) is associated with arrhythmogenicity and intra-atrial conduction delay, despite being optimal for visualization of the surgical field. It is sometimes difficult to treat atrial tachycardias (AT) that arise after STA. To investigate AT circuits that arise after STA in detail in order to identify the optimal ablation line, using ultra-high-resolution mapping (UHRM).We retrospectively analyzed 12 AT from 10 patients (median age 70 years, nine males) who had undergone STA surgery. The tachycardias were mapped using the Rhythmia mapping system (Boston Scientific, Natick, Massachusetts).The 12 STA-related AT (STA-AT) circuits were classifiable as follows according to location of the optimal ablation line: (1) peri-septal incision STA-AT (n = 3), (2) cavotricuspid isthmus (CTI) dependent STA-AT (n = 7), and (3) biatrial tachycardia (n = 2). Radiofrequency (RF) application terminated 11 of the 12 STA-AT. We found that difference in STA-AT circuit type was due to characteristics of the septal incision line made for STA. UHRM was important in identifying optimal ablation sites that did not create additional conduction disturbances in the right atrium (RA).ATs after STA involve complex arrhythmia circuits due to multiple and long incision lines in the RA. Accurate understanding of the arrhythmia circuit and sinus conduction in the RA after STA is recommended for treating post-surgical tachycardia in a minimally invasive manner.

Advances in surgical technique and prosthesis design have expanded the non-neoplastic indications for proximal femoral replacement (PFR) to include fracture nonunion, periprosthetic fracture, and severe bone loss in the setting of revision total hip arthroplasty (THA). The purpose of this study is to assess outcomes of PFRs used for nononcologic indications.A single-institution, retrospective, cohort survey study was conducted between August 2015-February 2020 of consecutive patients undergoing PFR for nononcologic indications in revision THA. Patient demographics, surgical variables, complications, and revision procedures were collected. Patient satisfaction and Oxford Hip scores were assessed via a telephone questionnaire. Implant survivorship was estimated using the Kaplan-Meier method.In total, 24 patients (27 PFRs) were available for analysis with an average age of 69.3 ± 12.9 years (range: 37-90). The average number of operations prior to PFR implantation was 3.1 ± 2.1 (range: 0-7). At a mean follow-up of 2.4 years (range: 0.5-5.1), the mean Oxford Hip Score was 31.7 ± 10.2, and mean patient satisfaction was 4.9/5. Six patients (20.7%) experienced a postoperative complication, with dislocation occurring in three patients (10.3%). None of the patients with dual mobility articulations (n = 4) had dislocation. Three-year survivorship was 85.2% (95% CI 71.8%-98.6%) with all-cause reoperations as the endpoint and 100% (95% CI 100.0%-100.0%) with revision for aseptic loosening as the endpoint.The current study demonstrates excellent short-term survivorship, satisfactory patient-reported outcomes, and high patient satisfaction following PFR for nononcologic indications during revision THA utilizing modern techniques. The most common mode of failure was dislocation requiring reoperation with revision to constrained acetabular components.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

We investigated the effects of chloroquine, an autophagy inhibitor, on doxorubicin-induced apoptosis in A549 cells.A549 cells were treated with doxorubicin, chloroquine, or both. Then, cytotoxicity was measured. The expression levels of caspases and mitogen-activated protein kinases were also quantified. In addition, the levels of doxorubicin-derived reactive oxygen species were measured.Chloroquine enhanced doxorubicin-induced apoptosis and oxidative stress and suppressed the doxorubicin-induced extracellular-signal-regulated kinase activation.Chloroquine enhances doxorubicin-induced and oxidative stress-mediated apoptosis. This mechanism may involve the dephosphorylation of extracellular-signal-regulated kinases.

To evaluate the efficacy of four decontamination protocols on contaminated healing abutments (HAs) and their effects on surface topography.Eighty contaminated single-use HA samples collected from human participants were stained with phloxine B and examined microscopically. The retrieved HAs were randomly divided into four test groups: (1) Autoclaving only (AU), (2) 5.25% sodium hypochlorite (NaOCl) + AU, (3) Electrochemical treatment (EC) + AU, (4) NaOCl + EC + AU, and positive control (contaminated without any treatment). Four new unused HAs served as negative controls (NC). The surface features were analyzed using stereo microscopy (SM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and optical profilometry.The lowest decontamination efficacy was observed for the AU group. The NaOCl + AU and EC + AU groups effectively removed residual contamination, whereas EC + AU showed better decontamination results than NaOCl + AU. SM, SEM, and EDS analyses revealed the best decontamination efficacy in the combined NaOCl + EC + AU group compared to the other groups. Surface roughness (Sa), developed surface area ratio (Sdr), and texture-aspect ratio (Str) in AU, NaOCl + AU, EC + AU, and NaOCl + EC + AU groups were not statistically significant compared to the NC group.The combination of NaOCl with subsequent EC can remove soft and hard deposits from the surface of HAs compared to NaOCl alone and EC alone, without altering the surface topography of HAs.

This study examined the relationships between fetal quantitative Doppler parameters and amniotic fluid N-terminal prohormone brain natriuretic peptide (afNT-proBNP) levels as a biomarker of the increased cardiac load in recipient twins with twin-to-twin transfusion syndrome (TTTS).This single-center, prospective study included all monochorionic diamniotic (MD) twin pregnancies that were diagnosed with TTTS and underwent fetoscopic laser surgery. Doppler flow was used to measure the pulsatility index (PI) of the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) of each recipient and donor twins. The afNT-proBNP levels of recipient twins were examined at the time of surgery. The Spearman or Pearson correlation coefficients were used to assess the relationships between afNT-proBNP levels and Doppler parameters.A total of 150 MD twin pregnancies were included. The afNT-proBNP levels of the recipient twins showed a stronger correlation with the DV-PI (r = 0.637; P 0.001) of recipient twins than with the UA-PI and MCA-PI of recipient twins. The Doppler parameters of donor twins were scarcely correlated with the afNT-proBNP levels of the recipient twins.A positive correlation between the DV-PI and afNT-proBNP levels of recipient twins with TTTS was observed. The recipient twin with an increased DV-PI is expected to be under a high cardiac load; therefore, DV-PI is a useful parameter for assessing increased NT-proBNP levels consecutively and noninvasively.This study was registered with Japanese Clinical Trial Registry "UMIN-CTR" ( http://www.umin.ac.jp/ctr/index-j.htm ; trial ID numbers UMIN000024486 and 000037702).

In metastatic renal-cell carcinoma (mRCC), recent clinical trials have shown efficacy of first-line combination therapy, as evidenced by better clinical outcome over target therapy. However, there are insufficient real-world evidences in mRCC patients in Japan.We performed a multicenter retrospective study of 72 mRCC patients who received nivolumab plus ipilimumab as first-line treatment between September 2018 and July 2021. Patient's characteristics, clinical outcomes and safety were retrospectively reviewed. We analyzed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients treated with combination therapy.Of all patients, the median age was 70 years (range, 36-86) and the major type of histology was clear cell RCC (n = 55; 76.4%). Progressive disease (n = 25; 34.8%) and irAEs (n = 22; 30.6%) were the most common causes for discontinuing treatment. Median PFS and OS seemed similar between patients who discontinued treatment because of irAEs and for patients who did not (p = 0.360 and p = 0.069, respectively). Importantly, for patients with synchronous metastatic disease at diagnosis (n = 56), nephrectomy before initiating nivolumab plus ipilimumab had a significantly positive impact on better OS when compared to that in patients without nephrectomy (p = 0.028).This study confirms efficacy and safety of nivolumab plus ipilimumab for mRCC patients in real-world settings. Furthermore, nivolumab plus ipilimumab was associated with a better outcome in patients who had undergone nephrectomy at diagnosis for synchronous mRCC.

OPC-61815, a prodrug of tolvaptan, is an injectable aquaretic drug. This study evaluated the tolerability of OPC-61815 in patients with congestive heart failure (CHF) who had difficulty with, or were incapable of, oral intake in a multicenter, uncontrolled, open-label Phase III study.Methods and Results: Forty-five patients were enrolled at 30 Japanese sites. OPC-61815 infusion was administered once daily; the 8 mg initial dose could be increased to 16 mg if the dose escalation criteria were met. Patients were treated for up to 5 days. Thirty-eight patients maintained the 8-mg dose and 7 had a dose increase to 16 mg; 41 completed the trial (34 completed early). One patient had mild hypernatremia. No significant safety concerns were observed with OPC-61815 administration at a starting dose of 8 mg and with dose escalation in accordance with the protocol-specified criteria. Treatment resulted in weight decrease (-3.01 kg); improvement or disappearance rates for other CHF symptoms (including edema, dyspnea, orthopnea, pulmonary congestion, and rales) indicated that treatment was effective. Urine excretion was increased 0-1 h after OPC-61815 administration and reached a maximum level at 1-2 h.The tolerability of once daily (up to 5 days) intravenous OPC-61815 (8 mg or 16 mg) was confirmed in patients with CHF who had difficulty with, or were incapable of, oral intake.

Purpose Selecting patients with coronary multivessel disease (MVD) or no stenosis using myocardial perfusion imaging (MPI) is challenging. We aimed to create a model to predict MVD using a combination of quantitative MPI values and background factors of patients. We also assessed whether patients in the same database could be selected who do not require rest studies (stress-only imaging). Methods We analyzed data from 1001 patients who had been assessed by stress MPI at 12 centers and 463 patients who had not undergone revascularization in Japan. Quantitative values based on MPI were obtained using cardioREPO software, which included myocardial perfusion defect scores, left ventricular ejection fractions and volumes. Factors in MPI and clinical backgrounds that could predict MVD were investigated using univariate and multivariate analyses. We also investigated whether stress data alone could predict patients without coronary stenosis to identify candidates for stress-only imaging. Results We selected summed stress score (SSS), rest end-diastolic volume, and hypertension to create a predictive model for MVD. A logistic regression model was created with an area under the receiver operating characteristics curve (AUC) of 0.825. To more specifically predict coronary three-vessel disease, the AUC was 0.847 when SSS, diabetes, and hypertension were selected. The mean probabilities of abnormality based on the MVD prediction model were 12%, 24%, 40%, and 51% for no-, one-, two-, and three-vessel disease, respectively (p Conclusion A model analysis combining myocardial SPECT and clinical data can predict MVD, and can select patients for stress-only tests. Our models should prove useful for clinical applications.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC.CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

The study aim was to examine whether flexible working time was associated with burnout and poor perceived health in relation to the work-related psychological/behavioral factors of self-endangering work behavior (SEWB), workaholism, work engagement, and job stressors. We analyzed data obtained from an Internet survey of 600 full-time Japanese employees. We also proposed a causal model using path analysis to investigate the overall relationships of burnout and perceived health to psychological/behavioral factors. The results indicated that flexible working time was associated with adverse work-related consequences and factors such as increased burnout, working hours, SEWB, workaholism, and job demands, and with positive factors such as improvement of work engagement. The path analysis suggested that burnout was caused by workaholism both directly and via SEWB, and by low job decision latitude, and was reduced by work engagement. Similarly, it was observed that poor health was caused by workaholism via SEWB, and reduced by work engagement. Thus, SEWB is driven by workaholism and plays a key role in the adverse health consequences of flexible working time. For workers to benefit from flexible working time, it is important to improve workaholism, SEWB, and low job decision latitude, and to develop work engagement in the workplace.

We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups.The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons.A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported.This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.

Background: Meniscal extrusion/translation has been used as an index for meniscal treatment. However, the relationship between meniscal displacement and the degree of meniscal tear or load–transmission function of the lateral meniscus (LM) remains unclear. Purpose: To clarify the relationship between the width of the radial tear of the LM and (1) meniscal displacement or (2) resultant force through the meniscus under axial compressive load in the porcine model. Study Design: Controlled laboratory study. Methods: Eight intact porcine knees with or without a partial radial tear at the midbody of the LM (involving 30%, 60%, or 90% of its width) were investigated. Reflective markers were attached to the outer wall of the anterior, anteromiddle, posteromiddle, and posterior segments of the LM. A 300-N axial load was applied at 2 flexion angles (30° and 60°), and the 3–dimensional forces and trajectories of the knees were recorded. Marker movements were simultaneously tracked using a motion capture camera system. After total meniscectomy of the LM, the recorded knee trajectories were reproduced, and the resultant force through the LM was calculated (a force carried only by the meniscus in response to a load applied to the whole knee joint). Results: At both flexion angles, the change in distance (mean ± SD) between the anterior and posterior markers under load increased significantly more in the anteroposterior direction in LMs with a 90% tear than in intact LMs (30°, 0.4 ± 0.3 vs 1.4 ± 0.8 mm, P = .004; 60°, 0.1 ± 0.7 vs 1.4 ± 1.0 mm, P < .001 [intact vs 90% tear]). The change in distance between the anteromiddle and posteromiddle markers at 30° also significantly increased in LMs with a 90% tear (0.2 ± 0.2 vs 1.3 ± 1.2 mm, P = .02 [intact vs 90% tear]). The resultant force was significantly lower in LMs with a 90% tear than in intact LMs (30°, 125 ± 47 vs 48 ± 20 N, P < .001; 60°, 93 ± 46 vs 43 ± 11 N, P = .002 [intact vs 90% tear]). We found no significant differences in either meniscal displacements or resultant forces between intact LMs and those with 30% or 60% tears. Conclusion: LMs with a 90%-width midbody radial tear lost load–transmission function with their displacement relative to the tibia primarily in the anteroposterior direction in the porcine model. Clinical Relevance: Even 1 mm of displacement after meniscal injury is evidence that the load–transmission function of the meniscus is greatly impaired. When a displaced torn LM is diagnosed in preoperative imaging, meniscal repair surgery should be considered.

Bone marrow edema (BME) after meniscus injury and risk factors for subchondral insufficiency fracture of the knee (SIFK) have been reported. However, their association with medial meniscus posterior root tear (MMPRT) remains unknown. We investigated the association of BME volume (BME-V), posterior shinycorner lesion (PSCL), and SIFK with MMPRT to examine the correlations between BME-V and medial meniscus extrusion (MME), PSCL and duration from injury to the time of magnetic resonance imaging (duration), and SIFK and duration. Twenty-nine patients who underwent surgery for MMPRT were included (mean age, 59.2; range, 39-84). The presence of PSCL, femoral BME-V (cm3), and SIFK grade (1-4) were evaluated. Preoperative factors, such as MME (mm) and duration (weeks), were investigated using multivariate linear/ logistic regression analyses. Multivariate linear regression analysis revealed duration as a significant factor for high-grade SIFK (p

We herein report a 43-year-old woman with Buerger's disease who presented with nephrotic syndrome, renal dysfunction, and mild hypertension. A kidney biopsy revealed focal segmental glomerulosclerosis (FSGS), but there were no findings associated with frequent secondary FSGS or a history of long-term hypertension. A small focal renal infarction was seen on 99mTc-dimercaptosuccinic acid renal scintigraphy, suggesting that FSGS was due to renal microinfarction associated with Buerger's disease. After the commencement of angiotensin-converting enzyme inhibitor therapy, the hypertension immediately improved, along with significant attenuation of proteinuria. Renal ischemia by vasoconstriction of the glomerular efferent arterioles in association with Buerger's disease may result in glomerular hyperfiltration followed by FSGS.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs.We studied the electroencephalograms (EEGs) of children6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep.The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035).EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

We herein report a case of mitochondrial disease with heart and intestinal tract involvement resulting in hemodynamic collapse. A 66-year-old woman was transferred to our hospital because of cardiogenic shock. Vasopressors were administered, and a circulatory support device was deployed. However, her hemodynamics did not improve sufficiently, and we detected abdominal compartment syndrome caused by the aggravation of chronic intestinal pseudo-obstruction as a complication. Insertion of a colorectal tube immediately decreased the intra-abdominal pressure, improving the hemodynamics. Finally, we diagnosed her with mitochondrial disease, concluding that the resulting combination of acute heart failure and abdominal compartment syndrome had aggravated the hemodynamics.

Extensive distal pancreatectomy (ExDP) can transect the pancreatic parenchyma more from the right side than conventional distal pancreatectomy (CDP) can. This study aimed to evaluate the short- and long-term outcomes of ExDP for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic body, located adjacent to the portal vein (PV).Medical records of 98 patients who underwent ExDP (n = 15) or CDP (n = 83) for PDAC were retrospectively reviewed. Short- and long-term outcomes of the two groups were compared. Propensity score matched analysis was additionally performed to minimize the impact of treatment allocation bias.In the total cohort, the CDP group had a significantly higher proportion of pancreatic tail lesions (P 0.01), higher proportion of males, and larger tumor size. Of the 15 patients who underwent ExDP, 11 could be matched. These differences of patients' characteristics were not observed after matching. Before and after matching, the duration of surgery, blood loss, rate of morbidity including pancreatic fistula, and postoperative course were comparable between the groups. The rate of recurrence and recurrence pattern were also not significantly different between the groups. ExDP for PDAC of the pancreatic body near the PV did not increase local or lymph node recurrence. The disease-free and overall survival did not differ between the groups.Surgical and oncological outcomes after ExDP for PDAC were acceptable and comparable to those after CDP. ExDP is a feasible procedure, and could be an option for the treatment of PDAC of the pancreatic body near PV.

Recent research conducted largely in the United States suggests that most people would like to change one or more of their personality traits. Yet almost no research has investigated the degree to which and in what ways volitional personality change (VPC), or individuals' active efforts toward personality change, might be common around the world. Through a custom-built website, 13,278 college student participants from 55 countries and one of a larger country (Hong Kong, S.A.R.) using 42 different languages reported whether they were currently trying to change their personality and, if so, what they were trying to change. Around the world, 60.40% of participants reported that they are currently trying to change their personalities, with the highest percentage in Thailand (81.91%) and the lowest in Kenya (21.41%). Among those who provide open-ended responses to the aspect of personality they are trying to change, the most common goals were to increase emotional stability (29.73%), conscientiousness (19.71%), extraversion (15.94%), and agreeableness (13.53%). In line with previous research, students who are trying to change any personality trait tend to have relatively low levels of emotional stability and happiness. Moreover, those with relatively low levels of socially desirable traits reported attempting to increase what they lacked. These principal findings were generalizable around the world. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Esophageal endoscopic submucosal dissection can cause esophageal strictures. Endoscopic balloon dilation is the standard treatment for esophageal strictures, but has complications, including perforation, and sometimes requires surgery. We report a case of perforation during endoscopic balloon dilation for esophageal stricture secondary to esophageal submucosal dissection that was successfully treated conservatively. A 66-year-old man with superficial carcinoma in the upper thoracic esophagus underwent circumferential endoscopic submucosal dissection with local steroid injections. Endoscopic balloon dilation was performed weekly for esophageal stricture. However, during the sixth procedure, an attempt to increase the size of the balloon to 13.5 mm resulted in perforation. The patient was treated conservatively using polyglycolic acid sheet with fibrin glue at the perforation site, which was fixed using an endoclip. However, the esophageal stricture persisted after the perforation was closed and Endoscopic balloon dilation was carefully repeated twice weekly up to a maximum of 17 mm, and the endoscope was able to pass through, and associated symptoms improved. This report indicates that endoscopic tissue shielding using polyglycolic acid sheet with fibrin glue and endoclip to correct perforation, followed by additional endoscopic balloon dilation, is an alternative to surgery.

We investigated whether N-terminal and C-terminal products of expressed in renal cell carcinoma/mesothelin (N-ERC and C-ERC) in peritoneal effluent can predict peritoneal permeability in patients undergoing peritoneal dialysis (PD).Thirty-seven peritoneal effluent samples were obtained from 26 PD patients. High transport status was determined by the peritoneal equilibration test as a dialysate/plasma ratio of creatinine (D/P Cr) ≥ 0.81. Effluent cancer antigen 125 (CA125) was used as a reference.Effluent N-ERC concentration was better correlated with D/P Cr than effluent C-ERC or CA125 concentration. In multivariate analyses, effluent N-ERC and C-ERC, but not CA125, were significant predictors of high transport status after adjusting for age, PD duration, and residual renal Kt/V. ROC analysis showed that effluent N-ERC was the best predictor of high transport status among those three biomarkers.Effluent N-ERC predicts increased peritoneal permeability in patients undergoing PD.