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Pulsed electric current sintering of molybdenum trioxide (MoO3) was carried out by one- and two-step pressurization methods for fabrication of irradiation targets used in the production of 99Mo and 99mTc nuclear medicines. At 550°C by the two-step pressurization method, a relative density of 93.1% was obtained while, by the one-step pressurization method, the relative density was 76.9%. Direct sample temperature measurements were conducted by a thermocouple inserted in a punch. By the two-step pressurization method, the sample temperature was higher than that by the one-step pressurization method even at almost the same die temperature. From voltage and current waveforms, it was indicated that the conductivity of the sample increased by the two-step pressurization method to increase the sample temperature and the relative density. The two-step pressurization method allows us to prepare dense targets at a low temperature from recycled and coarse-grained 98Mo enriched MoO3 powder.

The series of unsubstituted Sr2CaCu2O6 and iron-substituted Sr2CaCu2−xFexO6 () materials were produced by a high-pressure synthesis route and characterized using X-ray diffraction and SQUID magnetometry. The change of contained phase ratio was found at different substituent concentrations in the samples synthesized under the same conditions: unexpected growth of 0201 and CuO phase with decrease of iron content was observed. Synthesis temperature-dependence of obtained phase fractions was found for the samples with . The superconductivity transition was found for all obtained samples and the highest critical temperature was around 103 K. From the SQUID measurements distortions of the magnetic susceptibility curves were found; these were explained by the magnetic ordering arising at low temperatures. This magnetic ordering was associated with the magnetic moment appearing in iron-doped 0201 phase. [ABSTRACT FROM AUTHOR]

This paper describes a field shimming technology to obtain a spatially homogeneous magnetic field required for a high-resolution nuclear magnetic resonance (NMR) magnet under the influence of a screening current in a (RE)Ba2Cu3O7–x (REBCO) coil. Use of REBCO inner coils is one solution to realize a super-high field (>23.5 T, 1 GHz) NMR magnet. However, a REBCO coil generates a large amount of field error harmonics due to the inhomogeneous coil winding introduced by a thin tape conductor. In addition, the performance of a field correction coil and outer superconducting (SC) shim coils are significantly reduced due to the shielding effect of the screening current in the REBCO coil. Therefore, conventional shimming technology using SC shim coils and room temperature shim coils cannot adequately compensate those field error harmonics and high-resolution NMR measurements are not possible. In the present paper, an advanced field shimming technology including an inner SC shim coil and a novel type of ferromagnetic shim were installed in a 400 MHz low-temperature SC/REBCO NMR magnet. The inner SC shim coil and the ferromagnetic shim compensated for the reduction in the performances of the field correction coil and the SC shim coils, respectively. The field error harmonics were greatly compensated with the technology and a high NMR resolution <0.01 ppm was obtained. The results from the present work suggest an optimal shimming procedure for a super-high field NMR magnet with high-temperature superconductors inner coils, i.e. the best mix of shims. [ABSTRACT FROM AUTHOR]

An advanced Bi-2223 conductor with Ni–Cr reinforcement is a likely candidate to achieve a compact super-high field nuclear magnetic resonance (NMR) magnet capable of operation beyond 1 GHz (23.5 T). However, the conductors must show both high hoop stress tolerance, typically >300 MPa, and a small screening current-induced magnetic field, both of which are essential for a compact magnet generating a highly accurate field. These two conditions have not yet been demonstrated in a working coil. This is the first paper to systematically investigate both characteristics for a layer-wound coil made with the advanced Bi-2223 conductor operated mainly at 4.2 K in an external field of ≤17 T. The coil tolerated a hoop stress of 370 MPa, even though the conductor had a bending strain corresponding to a diameter of 120 mm. On the other hand, the coil showed a notable screening current-induced field in a low external field, which may be explained by weak-link and direct contacts between highly packed Bi-2223 filaments in the silver matrix. The field sharply decreased with increasing external field between 0–1 T. Thus, the conductor should be useful for inner coils in compact super-high field NMR magnets. [ABSTRACT FROM AUTHOR]

Background: The postoperative impact of short-term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1 month after surgery in determining postoperative survival and recurrence rates in patients with GC., Methods: We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1 month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v-ATL), and subcutaneous ATL (s-ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v-ATL and s-ATL measurements., Results: Patients with higher v-ATL and s-ATL had lower overall survival (OS) and recurrence-free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16-4.42; and P = 0.02) and RFS (HR 2.51; 95% CI 1.34-4.71; and P = 0.004) rates., Conclusion: A reduction in adipose tissue volume shortly after surgery (1 month) could potentially indicate an increased risk of recurrence and mortality in patients with GC., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background/aim: Post-gastrectomy lean body mass (LBM) decrease has a significant negative impact on postoperative survival in patients with cancer. This study investigated the effect of intake of at least one-third of the daily protein requirement at breakfast on the maintenance of LBM in patients during the first month post-gastrectomy., Patients and Methods: Among patients with gastric cancer who underwent curative distal gastrectomy between April 2011 and December 2018, without adjuvant chemotherapy, we evaluated 401 patients who had consumed more than the daily protein requirement in the first month postoperatively, using the FFQW82 nutrition intake questionnaire. Patients were divided into those who consumed more (≥1/3 intake group, n=160) and those who consumed less than one-third of the daily protein requirement at breakfast (<1/3 intake group, n=241). We compared the LBM reduction rate at one month postoperatively between groups. Univariate and multivariate analyses were performed to determine clinicopathological factors predicting LBM reduction at one month postoperatively., Results: The LBM reduction rate at one month post-curative distal gastrectomy was significantly higher in the <1/3 intake group than in the ≥1.3 intake group (p=0.01) at breakfast. Multivariate analysis showed that morning protein intake below one-third of the daily requirement independently predicted LBM reduction (odds ratio=1.75, 95% confidence interval=1.14-2.68, p<0.01)., Conclusion: Consuming at least one-third of the daily protein requirement at breakfast may be effective in maintaining LBM in patients undergoing curative distal gastrectomy. These results may be very important for prognosis, since maintaining LBM influences the continuation of adjuvant chemotherapy and thus survival after curative resection in patients with gastric cancer., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist., Patients and Methods: We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023., Results: A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively., Conclusion: About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/aim: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex., Patients and Methods: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis., Results: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females., Conclusion: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by Streptococcus pneumoniae . Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking., Objectives: To assess the antimicrobial efficacy of these two ceftriaxone regimens against S. pneumoniae using a murine model of pneumonia., Methods: The study employed three S. pneumoniae isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog 10  cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h., Results: The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against S. pneumoniae isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ± 0.19 Δlog 10 cfu/lungs versus -3.47 ± 0.17 Δlog 10  cfu/lungs, P  < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log 10  cfu/lungs versus -2.71 ± 0.37 Δlog 10  cfu/lungs, P  = 0.027). No significant difference in antimicrobial activity was observed against the S. pneumoniae isolate with a MIC of 4 mg/L between the two regimens (-0.33 ± 0.18 Δlog 10  cfu/lungs versus -0.42 ± 0.37 Δlog 10  cfu/lungs, P  = 0.684)., Conclusion: 2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by S. pneumoniae, with MICs of ≤2 mg/L., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background/aim: Radical resection after preoperative adjuvant chemotherapy (NAC) is a standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LAESCC), but its outcome remains unsatisfactory. In order to develop a personalized treatment program for LAES, we herein compared the survival prediction utility of five pre-NAC nutritional, inflammatory, and immune indexes in patients with LAESCC., Patients and Methods: We evaluated the survival of 203 patients with LAESCC who underwent radical resection after NAC from January 2011 to September 2019 for the following representative pre-NAC nutritional, inflammatory, and immune indices: modified Glasgow Prognostic Score, Prognostic Nutritional Index, C-reactive protein/albumin ratio, serum neutrophil/lymphocyte ratio, and Geriatric Nutrition Risk Index (GNRI) were evaluated for their impact on survival., Results: Of the five indices, GNRI was the best predictor of survival as determined by the area under the curve (p<0.05). When patients were divided into three groups according to the nutritional risk assessment of Bouillanne et al. using the pre-NAC GNRI, the 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly stratified (p<0.001). On multivariate analysis, the GNRI independently identified a poor OS group [group 1: hazard ratio (HR)=2.598, p=0.002; group 2: HR=6.257, p<0.001] and a high recurrence risk group (group 1: HR=1.967, p=0.016; group 2: HR=4.467, p<0.001)., Conclusion: In patients with LAESCC, GNRI may be the most accurate, reliable, and useful prognostic factor among the five major systemic inflammatory and nutritional indices., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility., Methods: Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines., Results: We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to β-lactam/β-lactamase inhibitors, carbapenems, and metronidazole., Conclusion: We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Based on gastric shape, patients with gastric cancer can be divided into storage (hook-shaped and ptotic stomach) and reverse outflow (steer-horn and cascade stomach) groups. In patients with gastric cancer, postoperative loss of lean body mass (LBM) is associated with a poor prognosis. This study investigated the influence of preoperative gastric shape on LBM loss 1 month after curative distal gastrectomy., Patients and Methods: Between May 2011 and May 2019, we enrolled 487 patients with pathological stage IA/IB/IIA gastric cancer who underwent curative distal gastrectomy and did not receive adjuvant chemotherapy. Patients were divided into storage (n=370) and outflow (n=117) groups according to whether barium was stored in the stomach during the preoperative fluoroscopic examination. Clinicopathological features, LBM 1 month after gastrectomy, and predictors of postoperative LBM loss were compared between the groups using multivariable logistic regression., Results: The incidence of >5% LBM loss and >7.5% body weight loss 1 month postoperatively were significantly higher in the storage group than in the outflow group (p=0.003 and p=0.009, respectively). Multivariable analysis revealed that gastric shape [odds ratio (OR)=3.30, 95% confidence interval (CI)=1.95-5.59, p<0.001], male sex (OR=3.20, 95% CI=2.07-4.96, p<0.001), and Roux-en-Y reconstruction (OR=1.69, 95% CI=1.08-2.64, p=0.02) were independent predictors of LBM loss. Postoperative dietary problems, especially dumping syndrome, diarrhea, and reflux were more common in the storage group (p<0.001)., Conclusion: Gastric shape may be a useful independent predictor of postoperative LBM loss in patients with gastric cancer undergoing distal gastrectomy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Radical esophagectomy after preoperative neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, careful treatment selection is required when considering organ function in elderly patients. Prealbumin, a rapid turnover protein, is a short-term dynamic nutritional index, and its relationship with long-term postoperative survival in various cancers has been previously reported. However, the association between serum prealbumin level before NAC and survival in elderly patients remains unclear. This study investigated the clinical significance of prealbumin level measurement before NAC in elderly patients with locally advanced ESCC who underwent surgery after NAC., Patients and Methods: Eighty patients aged ≥65 years diagnosed with cStage II/III ESCC and undergoing radical esophagectomy after cisplatin and 5-fluorouracil therapy as NAC, were included. The cutoff value of the serum prealbumin level before NAC was set at 18.2 mg/dl using receiver operating characteristic curve analysis, and postoperative complications, recurrence, and overall survival were compared between the low and high prealbumin groups., Results: There were no differences in patient background, clinicopathological characteristics, postoperative complications, or recurrence-free survival between the two groups. Overall survival (OS) was significantly worse in the low prealbumin group than in the high prealbumin group (5-year survival, 33.3% vs. 67.0%; p=0.0341). Furthermore, on univariate and multivariate analysis, low prealbumin level was an independent poor OS factor (p=0.036)., Conclusion: In elderly patients with locally advanced ESCC, serum prealbumin level before NAC may be a useful prognostic factor and may be important in selecting a treatment strategy that considers individual organ function., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Yersinia enterocolitica is a causative agent of food poisoning and has been isolated from pork and stream water, causing Yersinia enterocolitica in humans. The bacterium is divided into multiple serotypes and biotypes, among which serotypes O3 and O8 and biotypes 1B, 3, and 4 are frequently isolated in Japan. Biotype 3 can be classified as [VP+, Suc+], [VP-, Suc+], [VP-, Suc-] based on the biochemical properties. Among them, [O3, 3, VP-, Suc-] has been reported to be identified as Yersinia kristensenii in a simple identification kit. An increasing number of facilities in the field of microbiological testing are currently using mass spectrometers to identify species of microorganisms. However, there are many facilities where mass spectrometers have not yet been installed and microbial identification and susceptibility testing devices are used to identify bacterial species. No reports have described how the [O3, 3, VP-, Suc-] type, which is identified as Y. kristensenii in the simple identification kit, is identified by the microbial identification and susceptibility testing devices. In this study, 15 strains of Y. enterocolitica , which were previously isolated, serotyped, and biotyped from fecal culture tests at our hospital, were analyzed to see how these strains were identified in RAISUS S4, Microscan WalkAway, VITEK2 Blue, and BD Phoenix. [O3, 3, VP-, Suc-] was identified as Y. kristensenii in RAISUS S4, Microscan WalkAway, and VITEK2 Blue and as Y. enterocolitica in BD Phoenix. [O3, 3, VP-, Suc+], [O3, 4] and [O8, 1B] were identified as Y. enterocolitica . Therefore, when a sample was identified as Y. kristensenii by RAISUS S4, Microscan WalkAway, or VITEK2 Blue, the possibility that it was actually [O3, 3, VP-, Suc-] could not be ruled out. The possibility of Y. enterocolitica should be informed to attending physicians.

β-MoO 3 whiskers prepared by a thermal evaporation method and α-MoO 3 particles were irradiated in a nuclear reactor to produce 99 Mo/ 99m Tc radioisotopes via neutron capture. The irradiated targets were then dispersed in water to extract the 99 Mo/ 99m Tc isotopes. Of the 99 Mo formed in the β-MoO 3 whiskers, 64.0 ± 7.4% was extracted with water; by contrast, only 8.8 ± 2.6% of the 99 Mo formed in α-MoO 3 was extracted. By comparing these data to the 98 Mo concentration dissolved in water, we confirmed the hot-atom effect on both β-MoO 3 whisker and α-MoO 3 particle targets to transfer 99 Mo isotopes from irradiated samples to water. In addition, the β-MoO 3 whiskers exhibited a prominent hot-atom effect to transfer a higher ratio of 99 Mo isotopes into water. To the best of our knowledge, this research is the first demonstration of β-MoO 3 being used as an irradiation target in the neutron capture method. On the basis of the results, β-MoO 3 is considered a promising irradiation target for producing 99 Mo/ 99m Tc by neutron capture and using water for the radioisotope extraction process in the future.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents., Competing Interests: Declaration of competing interest Issei Tokimatsu received research funding from Asahi Kasei Pharma Corporation, and scholarship donations from Shionogi & Co., Ltd., and Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., and Pfizer Japan Inc. Makoto Miki hold shares in Daiichi Sankyo Co., Ltd., and received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Tomotaro Wakamura is an employee of Sumitomo Pharma Co., Ltd. Daisuke Kurai received research funding from Daiichi Sankyo Co., Ltd., and scholarship donations from Shionogi & Co., Ltd. Hiroki Tsukada received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Nobuki Aoki received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Hiroshige Mikamo received speaker honoraria from Nippon Becton Dickinson Company, Ltd., Astellas Pharma Inc., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Pfizer Japan Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co., Ltd., Gilead Sciences K.K., Saraya Co., Ltd., Tsumura & Co., Meiji Seika Pharma Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., Fukoku Co., Ltd., GlaxoSmithKline K.K., Kowa Company, Ltd., research funding from Fukoku Co., Ltd., Sekisui Medical Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., Saraya Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Roche Diagnostics K.K., ASKA Pharmaceutical Co., Ltd., Tosoh Corporation, Bruker Japan K.K., Abbott Diagnostics Medical Co., Ltd., Ortho Clinical Diagnostics K.K., Kyorin Pharmaceutical Co., Ltd., and scholarship donations from Asahi Kasei Pharma Co., Shionogi & Co., Ltd., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fukoku Co., Ltd., and Morii Co., Ltd. Atsushi Nakamura received speaker honoraria from Kyorin Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. Akira Ukimura received scholarship donations from Shionogi & Co., Ltd. Hiroshi Kakeya received speaker honoraria from MSD K.K., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Shionogi & Co., Ltd., Asahi Kasei Pharma Corporation., Astellas Pharma Inc., and Pfizer Japan Inc. Katsunori Yanagihara received speaker honoraria from Daiichi Sankyo Co., Ltd., MSD K.K., Astellas Pharma Inc., and Taisho Pharma Co., Ltd. (formerly Taisho Toyama Pharmaceutical Co., Ltd.), research funding from Fujifilm Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd., and scholarship donations from Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Kyorin Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Clinical staging in the eighth edition of the Union for International Cancer Control TNM classification (TNM8) is reported to predict the prognosis of patients with gastric cancer. However, there have been no reports on using the TNM8 for prognostic stratification of patients with adenocarcinoma of the esophagogastric junction (AEG). This study aimed to investigate whether it was possible to stratify the prognosis of patients who underwent curative surgery for Siewert type II/III AEG according to the TNM8 clinical stage (cStage)., Patients and Methods: This study included patients with Siewert type II/III AEG who underwent curative surgery between 2000 and 2019 at Kanagawa Cancer Center. Those who received neoadjuvant chemotherapy were excluded. We investigated the survival of patients with AEG of each TNM8 cStage., Results: This study included 138 patients, among whom 102 (74%) had Siewert type II and 36 (26%) had Siewert type III AEG. A total of 50, 38, 43, and seven patients were classified with cStage I, II, III, and IV, respectively. The median duration of follow-up of the survivors was 54.7 months. The 5-year overall survival rate of the entire cohort was 65.8%, whereas for patients with cStage I, II, III and IV was 81.6%, 69.0%, 54.3% and 14.3%, respectively. The hazard ratio with reference to cStage I was 1.83, 3.07, and 8.13 for cStage I, III, and IV, respectively, increasing in a stepwise manner., Conclusion: TNM8 Clinical staging is able to stratify the prognosis of patients with Siewert type II/III AEG., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Irinotecan and trifluridine/tipiracil (FTD/TPI) are fourth-line treatment options after third-line nivolumab for advanced gastric cancer (AGC). However, the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab remains unclear. This study aimed to evaluate the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab., Patients and Methods: We identified 137 AGC patients treated with nivolumab as third-line treatment in our institute between October 2017 and July 2021. Of these, we recruited 19 AGC patients who initiated irinotecan and 23 AGC patients who initiated FTD/TPI in the fourth-line setting until September 2021., Results: The median overall survival was 5.83 months for irinotecan and 6.31 months for FTD/TPI. Median time-to-treatment failure was 2.07 months for irinotecan and 1.64 months for FTD/TPI. While the frequency of all-grade diarrhea was higher in irinotecan (36% vs. 17%), grade ≥3 neutropenia tended to be higher in FTD/TPI (21% vs. 35%)., Conclusion: Irinotecan and FTD/TPI may be clinically useful as fourth-line treatments after nivolumab., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR's clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.

Fungemia is a fatal systemic infection that can occur in immunocompromised patients. Despite that, antifungal stewardship is spreading widely, but the mortality rate is extremely high, showing 40-60%. Loderomyces elongiporus is a newly morphologically detected pathogen, first described in 1994, followed by isolation in humans in 2008. It has been misrecognized as Candida parapsilosis . Recently, fever attributable to L. elongisporus fungemia cases has been reported, and the etiology and clinical features are still unknown. Here, we present three successfully treated L. elongisporus fungemia cases by echinocandin. In total, 11 cases were reviewed, including ours. Six of the eleven cases (55%) had external devices. All cases had some immunocompromised conditions or underlying diseases, such as diabetes mellitus, lung cancer, etc. Six patients survived, and the remaining five died. Seven patients who had received echinocandin initially survived. Risk factors for L. elongiporus fungemia overlap with those of candidemia. Even though there is no breakpoint for L. elongiporus , echinocandin can be a helpful treatment regimen for L. elongiporus fungemia.

Background/aim: Trifluridine/tipiracil (FTD/TPI) is an anticancer-agent that is administered as third-line or later chemotherapy for metastatic gastric/gastroesophageal junction cancer (mGC/GEJC). Although inflammatory and nutritional statuses have attracted attention as prognostic factors for patients with mGC/GEJC in this therapy, their usefulness has not been fully clarified. Thus, this study investigated the clinical significance of prognostic nutritional index (PNI), neutrophil/lymphocyte ratio (NLR), and NLR/serum albumin (Alb) ratio in patients administered FTD/TPI., Patients and Methods: This retrospective study included 64 patients who underwent FTD/TPI treatment for mGC/GEJC at Kanagawa Cancer Center, Kanagawa, Japan, between October 2019 and June 2022. Patients were divided into high and low PNI, NLR, and NLR/Alb groups according to their pretreatment blood data. This study evaluated the associations between the inflammatory and nutritional indexes and survivals., Results: Overall survival (OS) and progression-free survival (PFS) of patients with low PNI were significantly poorer than those with high PNI. However, low PNI was not an independent prognostic factor for OS and PFS. There was no significant association between NLR and OS or PFS. In contrast, the OS of patients with high NLR/Alb was significantly poorer than those with high PNI and low NLR/Alb. Furthermore, multivariate analysis showed that high NLR/Alb was an independent prognostic factor for OS., Conclusion: The NLR/Alb may be a useful prognostic factor in patients with mGC/GEJC being administered FTD/TPI as third-line or later chemotherapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We investigated the clinical influence of the prealbumin level on the gastric cancer survival and recurrence after curative treatment., Methods: This study included 447 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified., Results: A prealbumin level of 20 mg/dl was regarded as the optimal point of classification, considering the 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 80.7% and 65.0% in the low-prealbumin group, respectively, and 93.1% and 87.9% in the high-prealbumin group, respectively, a statistically significant difference (p < 0.001). The RFS rates at 3 and 5 years after surgery were 71.7% and 68.0% in the low-prealbumin group, respectively, and 90.1% and 84.7% in the high-prealbumin group, respectively, a statistically significant difference (p = 0.031). A multivariate analysis demonstrated that the prealbumin level was a significant independent risk factor for the OS and RFS. In addition, the rate of introduction of adjuvant chemotherapy was significantly lower and the frequency of peritoneal recurrence and lymph node recurrence significantly higher in the low-prealbumin group than in the high-prealbumin group., Conclusion: Prealbumin is a risk factor for the survival in patients who undergo curative treatment for gastric cancer. It is necessary to develop an effective plan of perioperative care and surgical strategy according to the prealbumin level., (© 2021. The Author(s).)

Preoperative inflammatory and nutritional statuses have potential prognostic effects on patients with gastric cancer (GC) after curative gastrectomy. We investigated the prognostic usefulness of the preoperative neutrophil-to-lymphocyte ratio/albumin ratio (NLR/Alb) in patients with GC. Among 483 patients who underwent gastrectomy for GC, the preoperative prognostic nutritional index (PNI), NLR, and NLR/Alb were calculated using preoperative blood test data. The patients were divided into the high and low PNI, NLR, and NLR/Alb groups. The associations of preoperative PNI, NLR, and NLR/Alb with clinicopathological features, 3-year (3Y) overall survival (OS) rates, and relapse-free survival (RFS) rates after gastrectomy for GC were evaluated. The number of female individuals and the C-reactive protein levels were significantly higher in the high- compared to the low-NLR/Alb group (both p < 0.05). The 3Y OS and 3Y RFS rates following gastrectomy were significantly lower in the high- compared to the low-NLR/Alb group (88.2% vs. 97.8%, p = 0.003 and 84.2% vs. 95.6%, p = 0.002, respectively). In multivariate analysis, high NLR/Alb could independently predict prognosis and recurrence (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.26-13.55; p = 0.02 and HR: 3.16; 95% CI: 1.34-7.45, p = 0.009, respectively). Preoperative NLR/Alb might be a useful prognostic factor for patients with GC after curative gastrectomy.

Introduction: A randomized control trial (RCT) is considered to be the highest level in the Evidence-Based Medicine (EBM) pyramid. While EBM is essential to make a practical tool such as a prognostic guideline, it has been unclear how many patients in the real world can be eligible for a randomized control trial (RCT). Patients and method: This study was performed to clarify if there is a difference in patients' profiles and clinical outcomes between the patients eligible and not eligible for any RCT. We reviewed all IE patients at our institute between 2007 and 2019. The patients were divided into two groups: those eligible for RCTs (RCT appropriate group) and those who were not (RCT inappropriate group). Exclusion criteria for clinical trials were set based on previous clinical trials. Results: A total of 66 patients were enrolled in the study. The median age was 70 years (range 18 to 87 years), and 46 (70%) were male. Seventeen (26%) of the patients were eligible for RCTs. Comparing the two groups, patients in the RCT appropriate group were younger and had fewer comorbidities. The disease severity was milder in the RCT appropriate groups than in the RCT inappropriate groups. Patients in the RCT appropriate group showed significantly longer overall survival times than those in the RCT inappropriate group (Log-Rank test, p < 0.001). Conclusions: We found a significant gap in patients' characteristics and clinical outcomes between the groups. Physicians should be aware that RCT can never reflect the real-world population.

Background/aim: SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection., Patients and Methods: We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival., Results: SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002)., Conclusion: SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

While acute empyema is a critical infectious disease showing a high mortality rate, there are no prognostic tools to evaluate the disease severity and prognosis for patients. We conducted a retrospective cohort to determine whether quick Sequential Organ Failure Assessment (qSOFA) and SOFA score can predict the disease severity and prognosis of acute empyema. A total of 53 patients were enrolled in the study. The mean age was 69 years and 41 patients (77%) were male. Twenty-two patients (42%) had multiple underlying diseases with the Charlson comorbidity index ≥3. The-30 days, and in-hospital deaths were 7 (13%) and 10 (19%), respectively. The area under the ROC curve of SOFA score and CCI for 30-day and in-hospital deaths were 0.814 (p = 0.073) and 0.752 (p = 0.082), 0.848 (p = 0.07) and 0.762 (p = 0.011), respectively. Univariate analysis showed that qSOFA ≥2 and SOFA score ≥2, isolation of potentially drug-resistant (PDR) pathogen, high CCI (≥3), performance status of 2-4, surgical intervention, and anaerobic bacteria involvement were prognostic factors. Of these, multivariate logistic regression analysis showed that qSOFA ≥2 and SOFA score ≥2 (p = 0.011), isolation of PDR pathogen (p = 0.005), and high CCI (≥3) (p = 0.015) were independently poor prognostic factors. We concluded that qSOFA and SOFA scores could predict the disease severity and prognosis in acute empyema. Additionally, isolation of PDR pathogens and high CCI could be poor prognostic factors for patients., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/aim: To clarify the clinical significance of measuring the mean corpuscular volume (MCV) of red blood cells before applying neoadjuvant chemotherapy (NAC) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who will receive NAC followed by curative resection., Patients and Methods: We retrospectively investigated 169 eligible patients at the Kanagawa Cancer Center between 2011-2018. The patients were divided into high and low-MCV groups. The cutoff value of the MCV was determined by the maximum χ 2 statistic value on the log-rank test and was set at 92.8 fl. Clinicopathological features and outcomes were compared between the two groups., Results: There was no significant association between the MCV and clinicopathological features. Both five-year recurrence-free survival (RFS) and overall survival (OS) in the high-MCV group were significantly poorer than those in the low-MCV group (RFS, p=0.026; OS, p=0.006). On multivariate analysis, a high-MCV was an independent predictive survival factor for RFS [hazard ratio (HR)=1.728; 95% confidence interval (CI)=1.033-2.891; p=0.037] and OS (HR=1.836; 95%CI=1.002-3.365; p=0.049)., Conclusion: Measurement of the MCV before NAC may be a useful prognostic biomarker in patients with locally advanced ESCC who will receive NAC followed by curative resection., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Epiregulin (EREG) is a ligand of the epidermal growth factor receptor (EGFR) and promotes tumour progression mainly by stimulating the EGF pathway. We investigated the clinical significance of EREG mRNA expression in cancer tissues from patients with gastric cancer (GC) in pathological (p) Stage II/III who have undergone curative surgery., Patients and Methods: Expression of EREG mRNA was measured in cancer tissues obtained from 253 patients with pStage II/III GC who underwent curative surgery. Patients were divided into groups based on high or low expression of EREG mRNA. We examined the relationship between EREG mRNA expression levels and clinicopathological features and survival., Results: Clinicopathological features did not vary between the high and low EREG mRNA expression groups. Overall survival was significantly lower in the high-expression group compared to that in the low-expression group (5-year survival probability: 55.0% vs. 73.0%; p=0.005). Multivariate analysis showed EREG mRNA expression to be an independent predictor of poor survival (hazard ratio=1.794; 95% confidence interval=1.186-2.712; p=0.006)., Conclusion: Expression of EREG mRNA in cancer tissue from patients with pStage II/III GC may be a useful prognostic marker after curative surgery., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence., Methods: We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses., Results: A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics., Conclusion: Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles., Case Presentation: A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died., Conclusion: Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to evaluate the short- and long-term outcomes in obese patients with gastric cancer undergoing totally laparoscopic total gastrectomy (TLTG) to clarify its feasibility in this population., Methods: We examined 136 consecutive patients who underwent TLTG for gastric cancer (GC) between 2013 and 2018. A total of 45 patients with a body mass index (BMI) ≥ 25 kg/m 2 were defined as the obese group (obese and overweight patients by the WHO classification), and 91 patients with a BMI < 25 kg/m 2 were defined as the non-obese group. Short- and long-term outcomes were compared, and the correlation between obesity and postoperative complications was examined in patients who underwent TLTG., Results: Although the operation time (min) was significantly longer in the obese group than in the non-obese group (329 vs 307, p = 0.002), there were no significant differences in the total volume of blood loss (mL) (118 vs 60, p = 0.059) or the rate of conversion to laparotomy between the two groups (2 vs 2, p = 0.466). Moreover, there was no significant difference in the incidence of postoperative complications between the two groups (16% vs 19%, p = 0.653). In the multivariate analysis, obesity was not identified as a risk factor for postoperative complications among patients who underwent TLTG. The rate of overall survival was not significantly different between the groups (p = 0.512)., Conclusion: TLTG is feasible for obese Japanese patients with GC. To validate the results of the present study, it is necessary to conduct a prospective study of a large population of patients with GC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/purpose: Rapid detection of β-lactamases is important in a recent situation where resistant bacteria are increasing. By using the drug susceptibility testing microfluidic device (DSTM), rapid screening of extended spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) has become possible., Methods: β-lactams and β-lactamase inhibitors were pre-fixed in the DSTM for use. A bacterial suspension in Mueller-Hinton broth (McF 0.25) was introduced into the device, and the effects of β-lactamase inhibitor on morphological changes caused by β-lactam were evaluated after 3 h incubation., Results: Clinical isolates genetically confirmed to produce β-lactamase were used. Of the 84 ESBL-producing strains, 80 strains (95%) turned to be ESBL positive, and five strains (6%) of them MBL were positive as well as ESBL. Four strains (5%) were negative for both ESBL and MBL. Of the 24 MBL-producing strains, 23 strains (96%) were positive for MBL. All the 43 AmpC-producing strains were negative for both ESBL and MBL. Of the 156 ESBL- and MBL-nonproducing strains, 155 strains (99%) were negative for both ESBL and MBL, and one strain was positive for ESBL. With this method, the detection sensitivity was 95% and the specificity was 100% for ESBL, whereas the detection sensitivity was 96% and the specificity was 98% for MBL. These results were not significantly different from the results of the disc diffusion method., Conclusion: The DSTM method allows rapid detection of β-lactamases in 3 h and may be a useful replacement for the disc diffusion method., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Transition-metal catalysis of substitution reactions of alkyl electrophiles by nitrogen nucleophiles is beginning to emerge as a powerful strategy for synthesizing higher-order amines, as well as controlling their stereochemistry. Herein, we report that a readily accessible chiral copper catalyst (commercially available components) can achieve the photoinduced, enantioconvergent coupling of a variety of racemic tertiary alkyl electrophiles with aniline nucleophiles to generate a new C-N bond with good ee at the fully substituted stereocenter of the product; whereas this photoinduced, copper-catalyzed coupling proceeds at -78 °C, in the absence of light and catalyst, virtually no C-N bond formation is observed even upon heating to 80 °C. The mechanism of this new catalytic enantioconvergent substitution process has been interrogated with the aid of a wide array of tools, including the independent synthesis of proposed intermediates and reactivity studies, spectroscopic investigations featuring photophysical and EPR data, and DFT calculations. These studies led to the identification of three copper-based intermediates in the proposed catalytic cycle, including a chiral three-coordinate formally copper(II)-anilido (DFT analysis points to its formulation as a copper(I)-anilidyl radical) complex that serves as a persistent radical that couples with a tertiary organic radical to generate the desired C-N bond with good enantioselectivity.

Background/aim: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC)., Patients and Methods: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs., Results: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment., Conclusion: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The low sensitivity of NMR spectroscopy is of historical concern in the field, and various approaches have been developed to mitigate this limitation. On the shoulder of giants, today one can routinely implement, for example, the pulse/Fourier transform NMR with the cross polarization together with the ultra-low temperature MAS DNP under high-field conditions. We show in this work this current opportunity should further be augmented by combining them with the cryogenic signal amplification. Our presented MAS DNP probe operates with the closed-cycle helium MAS system, and cools the internal preamplifier-duplexer module with the "return" helium gas on its way back to the compressor in the loop. The signal-to-noise (S/N) gain relative to the room-temperature measurements of a factor of 4.6 and 2.4 was found for the measurement using the cold- and room-temperature preamplifier, respectively, at the sample temperature of T = 20 K at B 0  = 16.4 T. The ratio of these factors reveals ∼ two-fold sensitivity improvement that results purely from the introduction of the cold signal amplification, i.e., noise reduction. Together with the increase of the thermal Boltzmann polarization at low temperatures, the combined S/N gain of max. ∼70-fold is possible without DNP. The DNP enhancement factor of ∼40 as we found in this work for a microcrystalline MLF sample may be multiplied to this gain. We also demonstrated the sensitivity improvement with a 13 C-detected 2D NCaCx spectrum, illustrating the generality of the S/N gain from combining DNP with the cold signal amplification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Evidenced based medicine (EBM) is necessary to standardize or treatment for infection since EBM is established based on the results of clinical trials. Entry criteria for clinical trials are very strict, and many patients have difficulties in being enrolled in any clinical trials regarding candidemia. It is questionable if the results of clinical trials reflect the real world of general medicine in this case., Patients and Methods: For the purpose of examining how many patients could join any randomized clinical trials for the treatment of candidemia, we reviewed all the candidemia patients in our institute during 2014-2018. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials., Results: A total of 70 patients was enrolled in this study. The median age was 73 years (range 36-93 years). Of these, 41 patients (59%) were male. As for site of infections, catheter related blood stream infection was most frequently seen in 37 (53%). Seventeen patients (24%) were classified as participation possible group and 53 patients (76%) were participation impossible group. Comparing the two groups, participation possible group patients have much better performance status, have less comorbidities and have longer overall survival times than participation impossible group patients., Conclusion: Only 24% of candidemia patients were eligible for the clinical trials. Thus, we can see that clinical trials might not correctly reflect the real world among candidemia patients., (Copyright © 2020. Published by Elsevier B.V.)

(1) Introduction: Evidence-based medicine (EBM) is necessary to standardize treatments for infections because EBM has been established based on the results of clinical trials. Since entry criteria for clinical trials are very strict, it may cause skepticism or questions on whether the results of clinical trials reflect the real world of medical practice. (2) Methods: To examine how many patients could join any randomized clinical trials for the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We reviewed all the pneumonia patients in our institute during 2014-2017. The patients were divided into two groups: patients who were eligible for clinical trials (participation-possible group), and those who were not (participation-impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials. (3) Results: A total of 406 patients were enrolled in the present study. Fifty-seven (14%) patients were categorized into the participation-possible group, while 86% of patients belonged to the participation-impossible group. Patients in the participation-possible group had less comorbidities and more favorable outcomes than those with the participation-impossible group. As for the outcomes, there were significant differences in the 30-day and in-hospital mortality rates between the two groups. In addition, the participation-possible group showed a longer overall survival time than the participation-impossible group ( p < 0.001 by Log-Rank test). (4) Conclusion: There is a difference in patients' profile and outcomes between clinical trials and the real world. Though EBM is essential to advance medicine, we should acknowledge the facts and the limits of the clinical trials.

Introduction: Patients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not., Patients and Methods: To evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients' characteristics, microbial profiles, and clinical outcomes were evaluated., Results: Both groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients' characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group., Conclusion: Unlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Procalcitonin (PCT) is an early diagnosis marker of sepsis/bacteremia. However, some reports refer to its lower responsiveness to gram-positive bacteremia. We retrospectively evaluated the PCT values at the onset of bacteremia in relation to severity index., Methods: Patients with bacteremia caused by two gram-negative bacteria (46 E. coli and 50 Klebsiella pneumoniae) and three gram-positive bacteria (45 S. aureus, 56 S. epidermidis, and 10 S. mitis) were studied. The plasma PCT and C-reactive protein (CRP) levels were compared between species and different Sequential Organ Failure Assessment (SOFA) score groups., Results: The median PCT level was higher in gram-negative than in gram-positive bacteremia in overall (13.09 vs. 0.50 ng/mL, p < 0.0001), in SOFA score≥4 group (28.85 vs.1.72 ng/mL, p < 0.0001) and in SOFA<4 group (2.64 vs. 0.42 ng/mL, p < 0.0001). Only 46%, and 11% of patients showed PCT ≥0.5 ng/mL in S. epidermidis, and S. mitis bacteremia, respectively. PCT was significantly better than CRP in discriminating gram-negative from gram-positive bacteremia (AUCROC; 0.828 and 0.634, p < 0.001), but it was low in Staphylococcus epidermidis bacteremia regardless of SOFA scores., Conclusions: PCT levels are lower in gram-positive bacteremia regardless of SOFA scores or the presence of shock. The conventional sepsis cutoff of 0.5 ng/mL may overlook certain proportions of gram-positive bacteremia., Competing Interests: Declaration of competing interest None of the authors have financial relationships with any commercial entity with an interest in the subject of this manuscript., (Copyright © 2020. Published by Elsevier B.V.)

Background/aim: The number of patients who have cardiovascular-morbidities and use antiplatelet and/or anticoagulation therapy is rapidly growing worldwide. The present study evaluated the safety and feasibility of gastrectomy for gastric cancer in patients who received antiplatelet and/or anticoagulation therapy in the perioperative period., Patients and Methods: Cases were selected from the medical records of consecutive patients who were diagnosed with gastric cancer and underwent complete resection at the Kanagawa Cancer Center from 2013 to 2017. The patients were divided into the antiplatelet and/or anticoagulation treatment group and the non-antiplatelet and/or anticoagulation treatment group., Results: Five hundred and six patients underwent gastrectomy for gastric cancer and were analyzed in the present study. Among them, 62 patients (12.3%) received anticoagulation therapy (anticoagulation group). When the anticoagulation and non-anticoagulation groups were compared, although there were some differences in patient background factors, the surgical findings, perioperative clinical course, and details of postoperative complications were similar. The incidence of postoperative bleeding was 0.8% (4/506) in all patients. The incidence of postoperative bleeding was 1.6% (1/62) in the anticoagulation group and 0.7% (3/446) in the non-anticoagulation group. Preoperative anticoagulation therapy was not identified as a significant independent risk factor for postoperative bleeding., Conclusion: These results suggest that curative gastrectomy for gastric cancer is safe and feasible, regardless of the perioperative use of antiplatelet and/or anticoagulation treatment. In addition, the perioperative use of antiplatelet and/or anticoagulation treatment was not a significant risk factor for postoperative bleeding after gastrectomy for gastric cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We investigated the impact of the pre-surgical C-reactive protein-to-albumin ratio (CAR) on survival and recurrence after curative treatment for gastric cancer., Patients and Methods: This study included 481 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified., Results: A CAR of 0.05 was regarded as the optimal critical point of classification considering the 3- and 5-year survival rates and patients were divided according to their CAR. The OS rates at 3 and 5 years after surgery were significantly higher at 92.5% and 87.9%, respectively, in the low-CAR group compared with 84.9% and 71.9%, respectively, in the high-CAR group. The corresponding RFS rates were 89.1% and 85.5%, and 81.0% and 72.2%, respectively, also a significant difference. A multivariate analysis demonstrated that the CAR was a significant independent risk factor for the OS and marginally significant independent risk factor for the RFS. In addition, the incidences of pancreatic fistula and abdominal abscess were significantly higher and the rate of introduction of adjuvant chemotherapy significantly lower in the high-CAR group., Conclusion: The CAR was a risk factor influencing survival in patients who underwent curative treatment for gastric cancer. An effective perioperative care plan and surgical strategy need to be developed according to the CAR., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

NMR spectroscopy permits real-time monitoring of reactions that involve changes in the spectra of reactants. MICCS (MIcro Channelled Cell for Synthesis monitoring) is a microfluidic chip for such purposes, which is used to rapidly activate reactions by mixing the reactant solutions in the chip inserted into the typical NMR tube. Although it allows monitoring of chemical reactions of small compounds, its simple mixing system dependent on diffusion in the microchannel was not suitable for macromolecules such as proteins with low diffusion rates. Here, we developed a new microfluidic chip based on MICCS by incorporating a mixer of split-and-recombination type within the microchannel. We applied it to monitoring of the protein-folding reaction in a stopped-flow mode. A solution of denaturant-unfolded RNase A was injected from a syringe pump into the microchip set inside the NMR magnet and mixed with a buffer for dilution to reach the folding condition. Immediately after dilution, the reaction was initiated and detected by a series of NMR measurements that were synchronized with activation and inactivation of the pump. The process was repeated for accumulation of the data. By analysing the change of the spectra by factor analysis, a kinetic constant of 0.57 min-1 was obtained., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)