Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Severe fibromyalgia alleviated by the unique muscle relaxation method of applying low force: A case report.

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.

Coexistence Case of Papillary Fibroelastoma and Lambl's Excrescence of the Left Heart, Which Is Occasionally Associated with Significant Stroke.

Papillary fibroelastoma (PFE) is a benign tumor that arises mostly from left-sided valves. PFE can cause stroke, and surgical resection may be needed. Lambl's excrescence (LE) is a filiform valvular lesion and is considered a possible cause of stroke. A 79-year-old man with light-headedness and left-sided hemiparesis was diagnosed with stroke. Transesophageal echocardiography (TEE) revealed a round-shaped mobile mass in the left ventricular outflow tract (LVOT), which was considered the cause of the stroke. Surgical resection was performed transaortically, and during surgery, a mass was incidentally detected on the noncoronary cusp (NCC), which was also resected followed by aortic valve replacement. Pathology confirmed that the mass in the LVOT was a PFE and that the filiform mass on the NCC was LE. We herein report a rare case of PFE in the LVOT and coexisting LE on the NCC. A careful examination via TEE helps to identify other possible causes of stroke hidden behind the obvious cause.

Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

Impedance-guided modified CLOSE protocol ablation can reduce ablation index necessary for pulmonary vein isolation in patients with atrial fibrillation.

BACKGROUND: Real-time monitoring of generator impedance drop is not considered in CLOSE protocol pulmonary vein (PV) isolation (PVI) in patients with atrial fibrillation (AF). We verified whether additional information of impedance drop could minimize ablation index required for PVI using modified CLOSE protocol (target ablation index ≥ 500 on anterior wall and ≥400 on posterior wall along with inter-lesion distance of 3-6 mm and maximum power of 35 W) without any adverse effect of procedural data and efficacy. METHODS: Sixty consecutive Japanese AF patients [paroxysmal AF: 43 (72 %) patients] underwent first-time PVI with modified CLOSE protocol with real-time monitoring of impedance drop (impedance-guided modified CLOSE protocol). Ablation tags were colored according to impedance drop and ablation was immediately terminated before reaching target ablation index if impedance drop of ≥10â€¯Ω was confirmed. Ablation index needed for PVI, first-pass PVI rate, other procedural data, and atrial tachyarrhythmia recurrence were evaluated. RESULTS: Mean ablation index and impedance drop on anterior and posterior walls were 437.6 ±â€¯43.5â€¯Ω and 10.2 ±â€¯2.6â€¯Ω and 393.3 ±â€¯27.4â€¯Ω and 9.3 ±â€¯2.2 Ω, respectively. First-pass PVI per PV pair was accomplished in 90/120 (75 %). No complications occurred. PV gaps after first-pass ablation were locationally most often found on right posterior wall than on the other parts (p < 0.001). There were no differences in mean contact force, impedance drop, and ablation index between walls with and without PV gaps after first-pass PV ablation. During a mean follow-up of 24 ±â€¯9 months, survival from atrial tachyarrhythmia recurrence was 51/60 (85 %) patients. CONCLUSIONS: Using additional generator impedance drop information may be useful to minimize radiofrequency current application to accomplish PVI with modified CLOSE protocol while maintaining efficacy and safety in Japanese AF population.

Method for Preparing Recombinant Galectin-2 Protein without Escherichia coli-Specific Post-translational Modifications.

Galectin-2 (Gal-2) is an animal lectin with specificity for ß-galactosides. It is predominantly expressed and suggested to play a protective function in the gastrointestinal tract; therefore, it can be used as a protein drug. Recombinant proteins have been expressed using Escherichia coli and used to study the function of Gal-2. The recombinant human Gal-2 (hGal-2) protein purified via affinity chromatography after being expressed in E. coli was not completely homogeneous. Mass spectrometry confirmed that some recombinant Gal-2 were phosphogluconoylated. In contrast, the recombinant mouse Gal-2 (mGal-2) protein purified using affinity chromatography after being expressed in E. coli contained a different form of Gal-2 with a larger molecular weight. This was due to mistranslating the original mGal-2 stop codon TGA to tryptophan (TGG). In this report, to obtain a homogeneous Gal-2 protein for further studies, we attempted the following methods: for hGal-2, 1) replacement of the lysine (Lys) residues, which was easily phosphogluconoylated with arginine (Arg) residues, and 2) addition of histidine (His)-tag on the N-terminus of the recombinant protein and cleavage with protease after expression; for mGal-2, 3) changing the stop codon from TGA to TAA, which is commonly used in E. coli. We obtained an almost homogeneous recombinant Gal-2 protein (human and mouse). These results have important implications for using Gal-2 as a protein drug.

Macrocytic anemia induced by selenium deficiency in the course of anorexia nervosa: A case report.

RATIONALE: Anorexia nervosa is characterized by an extreme fear of weight gain. Clinicians often prescribe meal replacement shakes if patients are unable or unwilling to consume typical foods. However, these shakes sometimes lack essential micronutrients, such as selenium, which may lead to health risks. Moreover, selenium deficiency induces macrocytic anemia. Herein, we present a case of a patient with anorexia nervosa with macrocytic anemia due to selenium deficiency, which was alleviated by selenium supplementation. PATIENT CONCERNS: An 18-year-old female was admitted to our hospital. The patient was diagnosed with anorexia nervosa. Ultimately, she was unable to walk independently because of fatigue and electrolyte disturbances. CLINICAL FINDINGS: On admission, the height, weight, and body mass index of the patient were 158.5 cm, 27.1 kg, and 10.8, respectively. Our treatment for anorexia nervosa showed relative effectiveness, and the patient's body weight recovered to 29.2 kg by day 60. However, the mean corpuscular volume increased from day 20, suggesting macrocytic anemia. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Despite our vitamin B12 and folic acid supplementation interventions, the mean corpuscular volume continued to rise. On day 60, the patient was diagnosed with selenium deficiency, and selenium administration of 100 µg/day was initiated. OUTCOMES: The macrocytic anemia in the patient was alleviated, and treatment for anorexia nervosa was continued in our hospital. LESSONS: To the best of our knowledge, this is the first case of macrocytic anemia induced by selenium deficiency with anorexia nervosa comorbidity, underscoring the importance of selenium supplementation in patients with anorexia nervosa, especially in those with macrocytic anemia.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

Unpredictable refeeding syndrome with severe hypophosphatemia in borderline personality disorder comorbidity: A case report.

RATIONALE: Refeeding syndrome (RS) is a fatal condition caused by rapid calorie intake during starvation. Self-neglected fasting in psychiatric disorders is associated with RS. However, overeating resulting from circumventing the clinician's instructions does not have a reportedly high risk of RS. PATIENT CONCERNS: A 47-year-old undernourished woman with borderline personality disorder was hospitalized for nausea, vomiting, and diarrhea. CLINICAL FINDINGS: She had not eaten much for 10 days and had lost weight (56.5-51.1 kg) over 3 weeks. No abnormalities were indicated on physical examination and imaging examinations. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Infectious diseases and malignancies were excluded from the differential diagnosis. On the third day of admission, the patient's serum phosphorus level significantly decreased to 0.7 mg/dL, and additional sodium phosphate was administered intravenously. On the fourth day, despite our instructions, the patient was found to be eating nonhospital food from the first day of admission. In conjunction with her history, a final diagnosis of RS was made. After appropriate treatments, the patient was discharged on the 15th day of hospitalization. The patient's nausea, vomiting, and diarrhea were improved. LESSONS: When undernourished patients have psychiatric disorders, including borderline personality disorder or schizophrenia, the occurrence of RS should be considered based on the patients' poor adherence to physicians' instructions.

Esophageal achalasia, diagnosed through the repeated manometry, alleviated using benzodiazepine: A case report.

RATIONALE: Idiopathic achalasia is an esophageal peristaltic dysfunction of the lower esophageal sphincter (LES). The initial symptom is progressive dysphagia. However, due to its rarity, it is often misdiagnosed as an esophageal disorder. High LES pressure on esophageal manometry is an essential finding for the diagnosis. PATIENT CONCERNS: A 55-year-old man was hospitalized with saliva-like vomitus, stuck-in-throat feeling of dysphagia, and weight loss. CLINICAL FINDINGS: On initial admission, gastrointestinal endoscopy, esophageal manometry, laboratory tests, and physical examination results were within normal limits. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Initially, the patient was diagnosed with globus sensation and recovered with medication. However, the symptoms recurred. He requested another examination on the second admission and was diagnosed with achalasia based on repeat esophageal manometry. The patient recovered after surgical treatment. LESSONS: When patients still suffer from these symptoms, there is a need to reconsider achalasia, even if it is initially excluded from the differential diagnosis. Medication is not a radical treatment; however, it sometimes ameliorates symptoms. Moreover, the psychosomatic approach can be useful in such cases.

Dispersed surface Ru ensembles on MgO(111) for catalytic ammonia decomposition.

Ammonia is regarded as an energy vector for hydrogen storage, transport and utilization, which links to usage of renewable energies. However, efficient catalysts for ammonia decomposition and their underlying mechanism yet remain obscure. Here we report that atomically-dispersed Ru atoms on MgO support on its polar (111) facets {denoted as MgO(111)} show the highest rate of ammonia decomposition, as far as we are aware, than all catalysts reported in literature due to the strong metal-support interaction and efficient surface coupling reaction. We have carefully investigated the loading effect of Ru from atomic form to cluster/nanoparticle on MgO(111). Progressive increase of surface Ru concentration, correlated with increase in specific activity per metal site, clearly indicates synergistic metal sites in close proximity, akin to those bimetallic N2 complexes in solution are required for the stepwise dehydrogenation of ammonia to N2/H2, as also supported by DFT modelling. Whereas, beyond surface doping, the specific activity drops substantially upon the formation of Ru cluster/nanoparticle, which challenges the classical view of allegorically higher activity of coordinated Ru atoms in cluster form (B5 sites) than isolated sites.

Spatial relationship of localized sources of persistent atrial fibrillation identified by a unipolar-based automated algorithm to complex fractionated atrial electrocardiograms and atrial low voltage areas.

INTRODUCTION: Spatial characteristics of localized sources of persistent atrial fibrillation (AF) identified by unipolar-based panoramic mapping software (CARTOFINDER) remain unclear. We evaluated spatial characteristics of bi-atrial AF localized sources in relation to complex fractionated atrial electrocardiograms (CFAEs) and atrial low voltage area (LVAs) (≤0.35 mV during AF). METHODS AND RESULTS: Twenty consecutive patients with persistent AF underwent bi-atrial voltage, CFAE, and CARTOFINDER mapping before the beginning of ablation (18 [90%] patients, initial procedure; 2 [10%] patients, repeat procedure). CFAEs were recorded using the interval confidence level (ICL) mode and defined as sites with a confidence level of ≥80% of maximal ICL number. We elucidated the following: (1) differences in the rate of AF localized sources and CFAEs inside or outside the atrial LVAs; (2) distribution of AF localized sources and CFAEs; and (3) distance between the closest points of AF localized sources and CFAEs. A total of 270 AF localized sources and 486 CFAEs were identified in 20 patients. AF localized sources were confirmed more often outside atrial LVAs than CFAEs (71% vs. 46% outside LVA, p < .001). AF localized sources and CFAEs were diffusely distributed without any tendency in bi-atria. Mean distance between closest AF localized sources and CFAEs was 22 ± 8 mm. CONCLUSION: AF localized sources identified by CARTOFINDER are different therapeutic targets as compared to CFAEs and could be confirmed both inside and outside atrial LVAs.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan.

Ribitol phosphate modifications to the core M3 O-mannosyl glycan are important for the functional maturation of α-dystroglycan. Three sequentially extended partial structures of the core M3 O-mannosyl glycan including a tandem ribitol phosphate were regio- and stereo-selectively synthesized: Rbo5P-3GalNAcß, Rbo5P-1Rbo5P-3GalNAcß, and Xylß1-4Rbo5P-1Rbo5P-3GalNAcß (Rbo5P, d-ribitol-5-phosphate; GalNAc, N-acetyl-d-galactosamine; Xyl, d-xylose). Rbo5P-3GalNAcß with p-nitrophenyl at the aglycon part served as a substrate for ribitol phosphate transferase (FKRP, fukutin-related protein), and its product was glycosylated by the actions of a series of glycosyltransferases, namely, ribitol xylosyltransferase 1 (RXYLT1), ß1,4-glucuronyltransferase 1 (B4GAT1), and like-acetyl-glucosaminyltransferase (LARGE). Rbo5P-3GalNAcß equipped with an alkyne-type aglycon was also active for FKRP. The molecular information obtained on FKRP suggests that Rbo5P-3GalNAcß derivatives are the minimal units required as the acceptor glycan for Rbo5P transfer and may serve as a precursor for the elongation of the core M3 O-mannosyl glycan.

Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication.

Oxysterol-binding protein (OSBP), which transports cholesterol and phosphatidylinositol 4-monophosphate (PtdIns[4]P) between different organelles, serves as a conserved host factor for the replication of various viruses, and OSBP inhibitors exhibit antiviral effects. Here, we determined the crystal structure of the lipid transfer domain of human OSBP in complex with endogenous cholesterol. The hydrocarbon tail and tetracyclic ring of cholesterol interact with the hydrophobic tunnel of OSBP, and the hydroxyl group of cholesterol forms a hydrogen bond network at the bottom of the tunnel. Systematic mutagenesis of the ligand-binding region revealed that M446W and L590W substitutions confer functional tolerance to an OSBP inhibitor, T-00127-HEV2. Employing the M446W variant as a functional replacement for the endogenous OSBP in the presence of T-00127-HEV2, we have identified previously unappreciated amino acid residues required for viral replication. The combined use of the inhibitor and the OSBP variant will be useful in elucidating the enigmatic in vivo functions of OSBP.

Imaging of isotope diffusion using atomic-scale vibrational spectroscopy.

The spatial resolutions of even the most sensitive isotope analysis techniques based on light or ion probes are limited to a few hundred nanometres. Although vibrational spectroscopy using electron probes has achieved higher spatial resolution1-3, the detection of isotopes at the atomic level4 has been challenging so far. Here we show the unambiguous isotopic imaging of 12C carbon atoms embedded in 13C graphene and the monitoring of their self-diffusion via atomic-level vibrational spectroscopy. We first grow a domain of 12C carbon atoms in a pre-existing crack of 13C graphene, which is then annealed at 600 degrees Celsius for several hours. Using scanning transmission electron microscopy-electron energy loss spectroscopy, we obtain an isotope map that confirms the segregation of 12C atoms that diffused rapidly. The map also indicates that the graphene layer becomes isotopically homogeneous over 100-nanometre regions after 2 hours. Our results demonstrate the high mobility of carbon atoms during growth and annealing via self-diffusion. This imaging technique can provide a fundamental methodology for nanoisotope engineering and monitoring, which will aid in the creation of isotope labels and tracing at the nanoscale.

Therapeutic options to reduce intravesical recurrence in newly diagnosed Ta high-grade bladder cancer according to risk stratification: A multicenter retrospective study.

OBJECTIVES: To evaluate the risk factors for intravesical recurrence in patients with newly diagnosed Ta high-grade non-muscle-invasive bladder cancer and the optimal management to reduce the risk of recurrence. METHODS: We retrospectively evaluated Ta high-grade bladder cancer in patients who were newly diagnosed by transurethral resection from January 2007 through October 2018. Using multivariate analyses, we evaluated the risk factors and therapeutic options affecting intravesical recurrence and stratified the patients according to the risk numbers. RESULTS: We included 390 patients and the median follow-up period was 31 months after the initial transurethral resection. According to multivariate analysis, having a previous history of upper urinary tract carcinoma, and multiple and sessile tumors were risk factors for intravesical recurrence (P = 0.001, P = 0.02 and P = 0.01, respectively). Risk groups were stratified according to these risk factors into favorable, intermediate and poor. In the entire cohort, induction and immediate intravesical instillation therapy were treatment options to reduce intravesical recurrence (P < 0.01 and P = 0.02, respectively). Analyses in each risk group showed that a second transurethral resection was the only therapeutic option to reduce intravesical recurrence in the favorable group (P = 0.048), whereas induction intravesical instillation therapy was effective in the intermediate and poor risk groups (P = 0.01 and P < 0.01, respectively), as was immediate intravesical instillation for the poor risk group (P < 0.001). CONCLUSIONS: Sessile, multiple tumors and a history of upper urinary tract carcinoma are risk factors for intravesical recurrence in Ta high-grade bladder cancer patients.

[Fever after Gemcitabine Administration is a Poor Prognostic Factor in Patients with Metastatic Urothelial Carcinoma : Multicenter Retrospective Study].

Gemcitabine (GEM) is currently a standard chemotherapeutic agent for metastatic urothelial carcinoma (mUC). Fever isknown to be an adverse effect of GEM ; however, itsincidence, etiology and clinical significance have not been evaluated. The objective of this study was to elucidate the characteristics and clinical significance of fever associated with GEM in patients with mUC receiving GEM plus cisplatin (GC) chemotherapy. Between 2005 and 2014, 184 patientswith mUC who received first-line GC therapy at 10 institutions were enrolled. GEM-associated fever (GEMAF) was defined as a body temperature ≥37.5ºC within 96 hours after administration of GEM with no evidence of specific conditions causing fever including infection. Clinical parametersbefore GC therapy were evaluated to determine predictorsof GEMAF. Furthermore, the impact of GEMAF on clinical outcomeswasals o evaluated. The median age was70 years and median follow-up was14.2 months. GEMAF wasobs erved in 44 patients (23.9%). In multivariate analysis, elevated C-reactive protein (CRP) before chemotherapy was an independent predictive factor for GEMAF (oddsratio 2.450, p＝0.041). There was a significant difference in progression-free survival (median 6.7 vs 8.0 months, p＝0.031) and cancer-specific survival (median 12.0 vs 15.8 months, p＝0.045) between patients with and without GEMAF. Results of this study suggest that GEMAF is a common adverse event of GC therapy for mUC and can be a poor prognostic factor. GEMAF may be associated with systemic inflammatory response induced by the tumor in patients with mUC.

[Necrotizing Fasciitis of the Right Thigh Caused by Emphysematous Pyelonephritis Due to a Staghorn Stone : A Case Report].

We report a rare case of necrotizing fasciitis in the thigh induced by emphysematous pyelonephritis due to a staghorn stone. A 60-year-old female was diagnosed with a staghorn stone in the right kidney at another clinic. We referred her to another hospital for indication of percutaneous nephrolithotripsy. However, she chose not to visit the hospital. One year and three months later, she was transported to the emergencyward of our hospital because of a high fever and right hip joint pain. The diagnosis of right emphysematous pyelonephritis with a perinephric abscess was diagnosed by computed tomography. Transurethral ureteral stenting and percutaneous abscess drainage were performed and her condition improved. However, two weeks after the initial treatment, she developed swelling and pain in the right thigh. Computed tomographyrevealed multiple areas of gas in the right thigh and urgent debridement was performed. Escherichia coli was isolated from the cultures of urine and debrided tissues. The patient received several treatments, including two additional debridements, negative pressure wound therapy, and antimicrobial chemotherapy. Three months after the first debridement, the open wound of the right thigh was completely closed. Necrotizing fasciitis in the thigh due to emphysematous pyelonephritis is very rare. A favorable outcome was obtained byprompt debridement and negative pressure wound therapyin this case.

Rapid Interchangeable Hydrogen, Hydride, and Proton Species at the Interface of Transition Metal Atom on Oxide Surface.

Hydrogen spillover is the phenomenon where a hydrogen atom, generated from the dissociative chemisorption of dihydrogen on the surface of a metal species, migrates from the metal to the catalytic support. This phenomenon is regarded as a promising avenue for hydrogen storage, yet the atomic mechanism for how the hydrogen atom can be transferred to the support has remained controversial for decades. As a result, the development of catalytic support for such a purpose is only limited to typical reducible oxide materials. Herein, by using a combination of in situ spectroscopic and imaging technique, we are able to visualize and observe the atomic pathway for which hydrogen travels via a frustrated Lewis pair that has been constructed on a nonreducible metal oxide. The interchangeable status between the hydrogen, proton, and hydride is carefully characterized and demonstrated. It is envisaged that this study has opened up new design criteria for hydrogen storage material.