Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

OBJECTIVE: This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. METHODS: This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. RESULT: The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927). CONCLUSION: It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.

Health guidance intervention mitigates the escalation of predicted comprehensive cardiovascular disease risk: Interrupted time series design.

INTRODUCTION: Metabolic syndrome increases the risk of cardiovascular events. Despite the Japanese healthcare system's efforts in early detection and intervention, particularly through Specific Health Checkup and Guidance programs, research on their effectiveness is limited. This study evaluated the impact of Specific Health Guidance on the predicted risk of atherosclerotic cardiovascular disease (ASCVD) in working-age Japanese individuals. METHODS: Employing an Interrupted Time Series (ITS) design, this study compared the trends in predicted ASCVD risk and each individual risk factor used for the prediction of ASCVD risk before and after intervention in individuals participating in the guidance. RESULTS: Analyses based on the ITS design indicated that participation in Specific Health Guidance programs, specifically the intensive level program, mitigates the increase trend of the predicted ASCVD risk. On the other hand, the impact on the trends of individual cardiovascular risk factors was minimal. CONCLUSIONS: The intensive level Specific Health Guidance appeared to reduce the increasing trend in ASCVD risk, emphasizing the importance of comprehensive risk assessment in evaluating health interventions. However, the results are limited owing to the specific demographics and short evaluation period. Further research is necessary to understand the long-term impacts and broader applicability.

Evaluating the association of body mass index with COVID-19 severity and mortality using Japanese administrative claims data.

INTRODUCTION: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population. METHODS: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group. RESULTS: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality. CONCLUSION: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population.

Changes in FeNO, d-ROMs, and BH4 by Intravenous L-Arginine in Children and Its Putative Role in Asthma Treatment.

Purpose: Pteridines are metabolites of tetrahydrobiopterin (BH4), being coenzymes for nitric oxide synthase (NOS). No study has clarified the relationship among pteridines and NOS, fractional exhaled nitric oxide (FeNO) generated by pteridines, and reactive oxygen species. In this study, we administered arginine, a precursor of NO, and confirmed changes in the levels of pteridines, FeNO, and reactive oxygen species and their relationship to clarify the pathogenesis of airway inflammation in which oxidative stress is involved, such as bronchial asthma. Patients and Methods: This is a prospective, randomized open-label study. Children, aged 2 to 15 years, who were scheduled for growth hormone stimulation tests and were able to undergo a respiratory function test were recruited. They were randomly divided into two groups: arginine-administered and control groups. In the former, L-arginine hydrochloride was intravenously administered. After administration, the levels of diacron-reactive oxygen metabolites (d-ROMs), serum pteridines, serum amino acids, and fractional exhaled NO (FeNO) were measured. Results: We analyzed 15 children aged 4 to 14 years. In the arginine-administered group, there was an increase in the FeNO level and a decrease in the d-ROMs level, reaching a peak 30 min after administration, compared with the control group. In addition, there was a decrease in the serum biopterin level and an increase in the d-ROMs level, reaching peak 60 min after administration. Conclusion: The administration of L-arginine increased the NO level and decreased the d-ROMs level. Due to this, biopterin may be consumed and decreased, leading to an increase in the d-ROMs level. As a reduction in reactive oxygen species leads to the relief of inflammation, arginine and biopterin may be useful for inhibiting inflammation.

Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial.

BACKGROUND: This study aimed to examine the preventive effect of amino acids on postoperative acute kidney injury (AKI). METHODS: This was single-center, patient- and assessor-blinded, randomized controlled trial. Patients who underwent aortic surgery with cardiopulmonary bypass were included. The intervention group received 60 g/day of amino acids for up to 3 days. The control group received standard care. The primary outcome was the incidence of AKI. We assessed the effect of amino acids on AKI using a Cox proportional hazards regression model. RESULTS: Sixty-six patients were randomly assigned to the control or intervention group. One patient in the control group withdrew consent after randomization. The incidence of AKI was 10 patients (30.3%) in the intervention group versus 18 patients (56.2%) in the control group (adjusted hazard ratio, 0.44; 95% confidence interval, 0.20-0.95; P = 0.04). CONCLUSIONS: This trial demonstrated a significant reduction in AKI incidence with amino acid supplementation. TRIAL REGISTRATION: jRCT, jRCTs051210154. Registered 31 December 2021, https://jrct.niph.go.jp/re/reports/detail/69916.

Advanced statistical analyses to reduce inconsistencies in bond strength data focused on donor factors: A six-factor analysis using linear mixed and nonlinear regression models.

PURPOSE: This study aimed to investigate the effects of the age and sex of tooth donors on dentin bond strength. METHODS: A total of 38 extracted teeth (12 male and 26 female donors; age range: 17-82 years) were used in this study. In addition to donor age and sex, four other microtensile bond strength (µTBS) test specimen factors were evaluated: dentin position, bonding area, presence of voids at the interface, and computed tomography (CT) values of dentin. The µTBS was measured immediately (24 h) and 6 months after storage in water. After the µTBS testing, linear mixed and nonlinear regression models were used to analyze the effects of these factors on the µTBS data. RESULTS: The results from the linear mixed model revealed that the bonding area (P = 0.02), presence of voids at the interface (P = 0.04), and storage time (P < 0.001) significantly affected bond strength. In contrast, no correlation was observed between the µ TBS and dentin position (P = 0.08) or sex (P = 0.07). The results of the nonlinear regression model with robust variance-covariance estimators revealed that age significantly affected bond strength (P < 0.001). In addition, a significant positive correlation was found between µTBS and age (P < 0.001), with nonlinearity (P = 0.002). However, no correlation was observed between the µTBS and CT values (P = 0.69) without nonlinearity (P = 0.39). CONCLUSIONS: These findings suggest that bond strength increases with age until 60 years but not afterward.

Immune Checkpoint Inhibitor Is Associated with Improved Survival in Advanced Non-small Cell Lung Cancer Occurring in Patients with Autoimmune Disease.

The use of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, clinical trials often exclude those with a history of autoimmune diseases (ADs) because of concerns regarding immune-related adverse events. Therefore, the efficacy of ICIs in advanced NSCLC patients with ADs should be evaluated. This study used administrative claims data from advanced treatment centers in Japan and identified patients with advanced NSCLC who began chemotherapy between December 2016 and January 2023. The patients were divided into four groups based on the presence of ADs and types of chemotherapy received. The association between ICI therapy and overall survival in the subgroups with or without ADs, and the association between the presence of AD and overall survival in patients who received ICI therapy and conventional chemotherapy, were analyzed using Cox proportional hazard regression, including therapy and presence of ADs and their interaction as covariates. These results were obtained using the inverse probability of treatment weighting. ICI therapy had a hazard ratio (95% confidence interval) for death in the subgroup of AD and non-AD patients of 0.88 (0.84-0.92) and 0.83 (0.71-0.97), respectively (p = 0.459 for interaction). For some specific ADs, including type 1 diabetes mellitus, the association between ICI therapy and decreased mortality was not observed. In conclusion, our study showed comparable associations between ICI therapy and reduced mortality in AD and non-AD subgroups of patients with advanced NSCLC. However, therapy strategies tailored to each AD type and thorough discussions regarding the risk-benefit profile are crucial.

Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival (JAMREDS): protocol of a multicenter prospective observational cohort study.

INTRODUCTION: Recent advances in dialysis therapy have made it possible to remove middle molecules. Removal of small-middle molecules, such as ß2-microglobulin (BMG), can now be achieved with conventional hemodialysis, and removal of large-middle molecules has become a target, particularly for 1-microglobulin (AMG, 33 kD). The AMG reduction rate has emerged as a target for improvement of various clinical symptoms, but the effects on prognosis have yet to be determined. The "Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival" (JAMREDS) was started in April 2020, with the goal of determining if the AMG reduction rate associates with the risk of mortality and cardiovascular disease (CVD) events. METHODS: JAMREDS is a prospective observational study in patients on hemodialysis (HD) to examine the effects of: 1) AMG reduction rate on survival outcome and CVD events; 2) dialysis treatment modalities (HD, intermittent infusion hemodiafiltration (iHDF), pre/post-dilution online HDF) on survival and CVD events (based on AMG reduction rates with treatment mode); and 3) AMG reduction rates on survival and CVD events in patients undergoing each therapy (iHDF, pre/post-dilution online HDF). The number of planned subjects was 4000 in pre-planning. Data are collected using RED-Cap, which is an EDC system. A total of 9930 patients were enrolled at the beginning of the study at 59 registered facilities. The JAMREDS observation period will continue until the end of 2023, after which the data will be cleaned and confirmed before analysis. CONCLUSION: This study may provide new evidence for the relationship between the amount of removed large-middle molecules (such as AMG) and the mortality and CVD risk. Comparisons with convection volumes will also be of interest. TRIAL REGISTRATION: UMIN000038457. Registered on 1st November, 2019: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043823.

Prediction of Cochlear Implant Effectiveness With Surface-Based Morphometry.

OBJECTIVE: This study aimed to determine whether surface-based morphometry of preoperative whole-brain three-dimensional T1-weighted magnetic resonance imaging (MRI) images can predict the clinical outcomes of cochlear implantation. STUDY DESIGN: This was an observational, multicenter study using preoperative MRI data. SETTING: The study was conducted at tertiary care referral centers. PATIENTS: Sixty-four patients with severe to profound hearing loss (≥70 dB bilaterally), who were scheduled for cochlear implant (CI) surgery, were enrolled. The patients included 19 with congenital hearing loss and 45 with acquired hearing loss. INTERVENTIONS: Participants underwent CI surgery. Before surgery, high-resolution three-dimensional T1-weighted brain MRI was performed, and the images were analyzed using FreeSurfer. MAIN OUTCOME MEASURES: The primary outcome was monosyllable audibility under quiet conditions 6 months after surgery. Cortical thickness residuals within 34 regions of interest (ROIs) as per the Desikan-Killiany cortical atlas were calculated based on age and healthy-hearing control regression lines. RESULTS: Rank logistic regression analysis detected significant associations between CI effectiveness and five right hemisphere ROIs and five left hemisphere ROIs. Predictive modeling using the cortical thickness of the right entorhinal cortex and left medial orbitofrontal cortex revealed a significant correlation with speech discrimination ability. This correlation was higher in patients with acquired hearing loss than in those with congenital hearing loss. CONCLUSIONS: Preoperative surface-based morphometry could potentially predict CI outcomes and assist in patient selection and clinical decision making. However, further research with larger, more diverse samples is necessary to confirm these findings and determine their generalizability.

Continuous positive airway pressure versus high-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

Age and Pre-operative HbA1c levels affect renal function compensation in living kidney donors.

OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

Lack of Association Between Immunotherapy and Improvement of Survival for Non-small Cell Lung Cancer Patients With Hemodialysis: A Nationwide Retrospective Cohort Study.

BACKGROUND: The number of patients undergoing hemodialysis continues to increase globally, and the incidence of cancer is high among these patients. Immune checkpoint inhibitors are widely used in patients with advanced cancer, especially non-small cell lung cancer (NSCLC); however, their effectiveness in hemodialysis patients is poorly documented. METHODS: This retrospective cohort study used data from a nationwide database. Patients diagnosed with NSCLC, undergoing hemodialysis, and who started chemotherapy between September 2008 and January 2023 were included. In the intention to treat (ITT) analysis, patients were divided into immune checkpoint inhibitor (ICI) and conventional chemotherapy group, and in the chronological analysis, patients were divided into 2 groups before and after ICI approval. Overall survival (OS) was analyzed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards analyses. A propensity score approach was applied to address confounding factors, and analyses were performed by weighting each patient with the inverse of the estimated propensity score. RESULTS: We identified 322 and 389 patients in the ITT and chronological analyses respectively. In both analyses, there were no notable difference of OS between 2 groups (P values by log-rank test 0.933 and 0.248, respectively). The hazard ratios for OS were 0.980 (95% confidence interval [CI]: 0.678-1.415) in the ITT analysis and 0.805 (95% CI: 0.531-1.219) in the chronological analysis. CONCLUSION: The ICI treatment and approval were not significantly associated with improvement of survival in patients with NSCLC undergoing hemodialysis.

Survey of students and guardians for assessing the early detection of auditory processing disorder and listening difficulties in school-age students.

OBJECTIVE: Auditory processing disorders (APD) and listening difficulties (LiD) are becoming increasingly prevalent in young adults. Our study surveyed students and their guardians to assess the early detection of APD and LiDs in students aged 6-18 years. We estimated the percentage of students with LiDs and assessed their guardians' perceptions during different school years. METHODS: This prospective study enrolled students from schools affiliated with Osaka Kyoiku University and their guardians. Both students and their guardians completed a basic assessment on demographics, and a questionnaire assessing LiD (completed by both students and guardians) and developmental problems (completed only by guardians). LiD was assessed in the following four domains: (i) auditory attention, (ii) auditory memory, (iii) auditory discrimination, and (iv) auditory restoration. The relationship between the school-year group and the total score for LiD and the differences between the students' and guardians' perceptions of the association between the school-year group and LiD domains were examined. RESULTS: Respondents comprised 743 students from 120 classes at three schools and 743 guardians. Hearing loss was reported by 26.5% of students and 26.1% of their guardians, with the majority indicating slight hearing loss. Compared with the students, their guardians more commonly indicated a normal response to all the questions related to LiD. The LiD scores reported by students increased with increasing school years and significantly deviated from those reported by their guardians. The students' scores in the auditory attention and auditory memory domains demonstrated significant increase with increasing school years, with the greatest increase in the auditory attention category. CONCLUSIONS: Students reported increasing severity of LiD with increasing school years, whereas their guardians underreported such symptoms, most significantly in the later school years. Therefore, screening for symptoms related to auditory attention could aid in the early detection of APD and LiD in school-age children.

Treatment sequencing after failure to alectinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Alectinib is the first-line therapy for anaplastic lymphoma kinase-positive non-small-cell lung cancer. Although some guidelines have recommended using other anaplastic lymphoma kinase inhibitors after alectinib failure, evidence for such regimens in patients who fail to respond to alectinib is limited. This study involved using administrative claims data from acute care hospitals in Japan. We extracted the data of 634 patients diagnosed with lung cancer between September 1, 2014, and January 31, 2023, who received alectinib treatment before treatment with another anaplastic lymphoma kinase inhibitor. We assessed distributions of patients according to their treatment sequencing and prognosis among three periods defined based on the initial marketing dates of lorlatinib and brigatinib. The type of anaplastic lymphoma kinase inhibitors after alectinib failure changed over time. In the most recent period, lorlatinib (58%) and brigatinib (40%) became predominant. Two-year overall survival improved over time (47%-84%), accompanied by an increased 2-year proportion of patients who continuously used anaplastic lymphoma kinase inhibitors after alectinib failure (13%-44%). The times to treatment discontinuation of the regimen between patients treated with lorlatinib and brigatinib were similar, with a hazard ratio of 1.02 (95% confidence interval, 0.64-1.64) in the period after marketing brigatinib. This study provides insights into the evolving treatment landscape for patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer who experience failed alectinib treatment and highlights the need for further studies and data accumulation to determine the optimal treatment strategy.

Vascular access site complications after transfemoral transcatheter aortic valve implantation: a comparison of open and percutaneous puncture approaches.

Background: In transfemoral transcatheter aortic valve implantation (TF-TAVI), which approach has lower vascular access site complications between the open puncture (OP) and percutaneous puncture (PP) approaches is still controversial. Moreover, few studies have analyzed risk factors for vascular access site complications in TF-TAVI. This study aimed to compare vascular access site complications between the OP and PP approaches in patients undergoing TF-TAVI and access risk factors for vascular access site complications. Methods: Three hundred fifty-one patients who underwent TF-TAVI via the PP (n=251) and OP (n=100) were retrospectively examined. Results: Incidence of vascular access site complications was 7.0% in the OP group and 8.4% in the PP group (P=0.828). Two deaths from vascular access site complications occurred in the PP group. After performing inverse probability weighting (IPW), regression analysis showed that PP was associated with a significantly higher odds of vascular access site complications [odds ratio =2.033; 95% confidence interval (CI): 1.397-2.958; P<0.001]. Common femoral artery (CFA) depth (hazard ratio =1.04; 95% CI: 1.000-1.070; P=0.045) and sheath/CFA diameter ratio (hazard ratio =971; 95% CI: 22.6-41,700; P<0.001) were independent complication risk factors. In patients with CFA depth ≥35 mm, the incidence of vascular access site complications was higher with PP than OP. Sheath/CFA diameter ratio ≥0.9 was associated with increased risk of vascular injury with both approaches. Conclusions: The incidence of vascular access site complications in patients undergoing TF-TAVI was significantly lower with OP than PP after IPW. OP may be preferable when CFA depth is ≥35 mm. When the sheath/CFA diameter ratio is ≥0.9, approaches other than the TF approach should be considered.

Real-world evidence on levodopa dose escalation in patients with Parkinson's disease treated with istradefylline.

OBJECTIVE: Istradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson's disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline. METHODS: Using Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, ≥400 to <600, ≥600 mg/day) and treatment with or without monoamine oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or dopamine agonists before istradefylline initiation. RESULTS: The analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving ≥600 mg/day levodopa or not receiving MAO-B inhibitors or COMT inhibitors demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline (≥600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-B inhibitors, -1.819 mg/day each month, p = 0.004; no COMT inhibitors, -1.412 mg/day each month, p = 0.027). CONCLUSIONS: This real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving ≥600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.

A Phase I/II Clinical Trial of Intradermal, Controllable Self-Replicating Ribonucleic Acid Vaccine EXG-5003 against SARS-CoV-2.

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a key role in reducing morbidity and mortality from coronavirus disease 2019 (COVID-19). We conducted a double-blind, placebo-controlled phase I/II trial to evaluate the safety, tolerability, and immunogenicity of EXG-5003, a two-dose, controllable self-replicating RNA vaccine against SARS-CoV-2. EXG-5003 encodes the receptor binding domain (RBD) of SARS-CoV-2 and was administered intradermally without lipid nanoparticles (LNPs). The participants were followed for 12 months. Forty healthy participants were enrolled in Cohort 1 (5 µg per dose, n = 16; placebo, n = 4) and Cohort 2 (25 µg per dose, n = 16; placebo, n = 4). No safety concerns were observed with EXG-5003 administration. SARS-CoV-2 RBD antibody titers and neutralizing antibody titers were not elevated in either cohort. Elicitation of antigen-specific cellular immunity was observed in the EXG-5003 recipients in Cohort 2. At the 12-month follow-up, participants who had received an approved mRNA vaccine (BNT162b2 or mRNA-1273) >1 month after receiving the second dose of EXG-5003 showed higher cellular responses compared with equivalently vaccinated participants in the placebo group. The findings suggest a priming effect of EXG-5003 on the long-term cellular immunity of approved SARS-CoV-2 mRNA vaccines.

Electrospray mass spectrometry method to prevent the reduction of hexavalent to pentavalent chromium.

RATIONALE: Electrospray mass spectrometry (ESI-MS) is one of the most effective methods for assessing the state of metals in solution. For ions with a redox potential close to ~0.55 V, such as Cr6+ , reduction of the metal in solution occurs in the ESI-MS system. In our studies, it was observed that [HCrO4 ]- undergoes reduction, resulting in the formation of [CrO3 ]- . The precise mechanism remains ambiguous. The reduction of hexavalent chromium to pentavalent chromium is supported by Frost diagrams, reinforcing our confidence in the validity of the ESI-MS measurement method. The reduction mechanism in ESI-MS was clarified, and a system was devised to eliminate electron donation during the reduction of Cr6+ in solution. METHODS: To determine the state of Cr6+ by ESI-MS, CrO3 in solid form was dissolved in ultrapure water to prepare a solution of 500 × 10-6  mol/L (µM) concentration. The pH was adjusted to 4.0, 5.3, 6.3, 8.2 and 9.1 and subsequently measured. CrO3 solutions with various concentrations of 10, 100 and 500 µM were prepared and adjusted to a pH of ~7 using tetramethylammonium hydroxide to measure Cr6+ under different conditions. RESULTS: Cr6+ in solution was soluble and existed as an oxoacid with a negative charge independent of pH. Cr6+ was stable over a wide pH range at various concentrations. The ESI-MS method determined the negative ion [HCrO4 ]- as the stable ion, but [CrO3 ]- was also present as a byproduct. Therefore, we were interested in the presence of other species, such as [CrO3 ]- , which could have formed owing to the reduction of Cr6+ . CONCLUSIONS: In ESI-MS system, it undergoes reduction to form [CrO3 ]- . The high flow rate of ultrapure water in pump insulated the acceptance of electrons by Cr6+ preventing its reduction. Further in-depth ESI-MS studies could explain the complex formation and behavior of Cr6+ in aqueous solution.

Renin-angiotensin-aldosterone system inhibitors are associated with improved paclitaxel-induced peripheral neuropathy in lung cancer: a study using administrative claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients' quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin-angiotensin-aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN). METHODS: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine-Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding. RESULTS: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762-0.929). The result was consistent in various sensitivity analyses and important subgroup analyses. CONCLUSIONS: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer.