Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

Broken Screw Rotational Symmetry in the Near-Surface Electronic Structure of AB-Stacked Crystals.

We investigate the electronic structure of 2H-NbS_{2} and h-BN by angle-resolved photoemission spectroscopy (ARPES) and photoemission intensity calculations. Although in bulk form, these materials are expected to exhibit band degeneracy in the k_{z}=π/c plane due to screw rotation and time-reversal symmetries, we observe gapped band dispersion near the surface. We extract from first-principles calculations the near-surface electronic structure probed by ARPES and find that the calculated photoemission spectra from the near-surface region reproduce the gapped ARPES spectra. Our results show that the near-surface electronic structure can be qualitatively different from the bulk electronic structure due to partially broken nonsymmorphic symmetries.

A Machine Learning Approach for Prediction of CDAI Remission with TNF Inhibitors: A Concept of Precision Medicine from the FIRST Registry.

INTRODUCTION: This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6 months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA). METHODS: Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation. RESULTS: Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input. CONCLUSIONS: While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.

This study aims to enhance the management of rheumatoid arthritis by predicting the likelihood of achieving the treatment target­Clinical Disease Activity Index remission within 6 months of initiating tumor necrosis factor inhibitors. In rheumatoid arthritis, the goal is often Clinical Disease Activity Index remission, and the standard approach involves using medications like methotrexate and biologic/targeted synthetic disease-modifying antirheumatic drugs. However, not all patients respond to these treatments, leading to a trial-and-error process of changing medications. Tumor necrosis factor inhibitors are commonly used as the initial biologic/targeted synthetic disease-modifying antirheumatic drugs for patients who do not respond adequately to methotrexate; however, tumor necrosis factor inhibitor treatment may not achieve effective outcomes for all patients. The study, using a cohort of patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor, has developed a model predicting Clinical Disease Activity Index remission with tumor necrosis factor inhibitors. The models use only standard clinical parameters, therefore no special examination or additional cost is required for the predictions. This approach holds the potential to improve rheumatoid arthritis management by reducing the need for trial-and-error approaches and facilitating more personalized and effective treatment strategies. While further validation is necessary, the study also suggests that creating cost-effective models tailored to specific regions or institutions is possible.

Diverse Plantarflexor Module Characteristics Influence Immediate Effects of Plastic Ankle-Foot Orthosis on Gait Performance in Patients With Stroke: A Cross-sectional Study.

OBJECTIVE: To investigate the immediate effects of plastic ankle-foot orthosis (AFO) on locomotor performance in patients with stroke and determine how such effects might undergo alteration when distinct plantarflexor (PF) module subtypes are considered. DESIGN: Cross-sectional study. SETTING: Two university hospitals. PARTICIPANTS: Fifty-two patients with stroke and 21 of those without stroke (N=73). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Motor modules were identified through non-negative matrix factorization, and participants were classified into 3 groups: independent-normal-timing, independent-altered-timing, and merged PF modules. To assess the effects of the AFO, gait measurements reflecting locomotor performance were obtained with and without the presence of the plastic AFO for each group. RESULTS: The independent-altered-timing group had increased paretic propulsion, greater non-paretic step length, and faster walking speed after the administration of the plastic AFO; however, these significant changes were not observed in the independent-normal-timing and merged PF module groups. Notably, patients in the independent-normal-timing and merged PF module groups exhibited longer paretic stance times. CONCLUSION: This study suggests that the immediate effects of plastic AFO depend on the PF module subtype. These findings can potentially guide clinical decision-making regarding AFO selection for stroke rehabilitation in patients with diverse gait control characteristics.

Enhancing carbapenem antimicrobial dosing optimization: synergy of antimicrobial stewardship teams and ward-based clinical pharmacists.

Antimicrobial-product package inserts and insufficient staffing impede routine carbapenem monitoring in the inpatient setting in Japan. The collaboration between antimicrobial stewardship teams and clinical pharmacists was associated with a sustained improvement in carbapenem dosing optimization. Our findings could be of use to countries with inadequate monitoring of carbapenem antimicrobial use.

Involvement of CX3CR1+ cells appearing in the abdominal cavity in the immunosuppressive environment immediately after gastric cancer surgery.

BACKGROUND: Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. METHODS: Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. RESULTS: CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death-1 expression. CONCLUSIONS: Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.

Evaluation of virus removal in membrane bioreactor (MBR) and conventional activated sludge (CAS) processes based on long-term monitoring at two wastewater treatment plants.

The membrane bioreactor (MBR) process always offers better wastewater treatment than conventional activated sludge (CAS) treatment. However, the difference in their efficacy of virus reduction remains unknown. To investigate this, we monitored virus concentrations before and after MBR and CAS processes over 2 years. Concentrations of norovirus genotypes I and II (NoV GI and GII), aichivirus (AiV), F-specific RNA phage genotypes I, II, and III (GI-, GII-, and GIII-FRNAPHs), and pepper mild mottle virus (PMMoV) were measured by a quantitative polymerase chain reaction (qPCR) method at two municipal wastewater treatment plants (WWTPs A and B) in Japan. Virus concentration datasets containing left-censored data were estimated by using both maximum likelihood estimation (MLE) and robust regression on order statistics (rROS) approaches. PMMoV was the most prevalent at both WWTPs, with median concentrations of 7.5 to 8.8 log10 copies/L before treatment. Log10 removal values (LRVs) of all viruses based on means and standard deviations of concentrations before and after treatment were consistently higher following MBR than following CAS. We used NoV GII as a model pathogen in a quantitative microbial risk assessment of the treated water, and we estimated the additional reductions required following MBR and CAS processes to meet the guideline of 10-6 DALYs pppy for safe wastewater reuse.

The efficacy of vaginal treatment for non-Lactobacillus dominant endometrial microbiota-A case-control study.

AIM: Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora. METHODS: This study included patients diagnosed with repeated implantation failure-defined as failure to achieve pregnancy after two or more transfers of viable embryos-who were classified as non-Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1-week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1-week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%. RESULTS: Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242). CONCLUSIONS: This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies.

Intravenous lipid emulsion for local anaesthetic systemic toxicity in pregnant women: a scoping review.

BACKGROUND: Local anaesthetic systemic toxicity (LAST) is a rare but life-threatening complication that can occur after local anaesthetic administration. Various clinical guidelines recommend an intravenous lipid emulsion as a treatment for local anaesthetic-induced cardiac arrest. However, its therapeutic application in pregnant patients has not yet been established. This scoping review aims to systematically identify and map the evidence on the efficacy and safety of intravenous lipid emulsion for treating LAST during pregnancy. METHOD: We searched electronic databases (Medline, Embase and Cochrane Central Register Controlled Trials) and a clinical registry (lipidrescue.org) from inception to Sep 30, 2022. No restriction was placed on the year of publication or the language. We included any study design containing primary data on obstetric patients with signs and symptoms of LAST. RESULTS: After eliminating duplicates, we screened 8,370 titles and abstracts, retrieving 41 full-text articles. We identified 22 women who developed LAST during pregnancy and childbirth, all presented as case reports or series. The most frequent causes of LAST were drug overdose and intravascular migration of the epidural catheter followed by wrong-route drug errors (i.e. intravenous anaesthetic administration). Of the 15 women who received lipid emulsions, all survived and none sustained lasting neurological or cardiovascular damage related to LAST. No adverse events or side effects following intravenous lipid emulsion administration were reported in mothers or neonates. Five of the seven women who did not receive lipid emulsions survived; however, the other two died. CONCLUSION: Studies on the efficacy and safety of lipids in pregnancy are scarce. Further studies with appropriate comparison groups are needed to provide more robust evidence. It will also be necessary to accumulate data-including adverse events-to enable clinicians to conduct risk-benefit analyses of lipids and to facilitate evidence-based decision-making for clinical practice.

Safety and dose-finding trial of tadalafil administered for fetus in labor: A phase I clinical study.

AIM: This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy. METHODS: The study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery. RESULTS: A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration. CONCLUSIONS: The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.

Factors affecting the willingness of nursing care staffs for cooperation with heart failure care and the role of internet video education.

Background: With the aging of heart failure (HF) patients, collaboration between medical and nursing care facilities is essential for HF care. The aims of this study were: (1) to identify the factors that affect willingness of nursing care staffs to cooperate with HF care; (2) to test whether the internet video education is useful in improving their willingness to collaborate. Methods: A web-based questionnaire was e-mailed to 417 registered medical corporations that operated nursing care facilities in the prefecture where the authors work. Medical and care staff working at each facility were asked their willingness to cooperate with HF care and their problems about collaboration. Machine learning analysis was used to assess the factors associated with unwillingness to cooperate. After watching a 6-min YouTube video explaining HF and community collaboration, we reaffirmed their willingness to cooperate. Results: We received responses from 76 medical and care staff members. Before watching the video, 32.9% of participants stated that they were unwilling to cooperate with HF care. Machine learning analysis showed that job types, perceived problems of collaboration, and low opportunities to learn about HF were associated with unwillingness to cooperation. After watching the video, we observed an increase from 67.1% to 80.3% (p < 0.05) of participants willing to cooperate with HF care. Conclusions: Job types, perceived problems of collaboration, and low opportunities to learn about HF are associated with unwillingness of nursing care staff for HF care. Internet videos are potential learning tool that can easily promote community collaboration for HF.

Flowchart for predicting achieving the target area under the concentration-time curve of vancomycin in critically ill Japanese patients: A multicenter retrospective study.

INTRODUCTION: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients. METHODS: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUCfollow-up) and target AUCfollow-up achievement was defined as an AUC of 400-600 µg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT). RESULTS: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUCfollow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUCfollow-up of 400-600 µg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m2 or higher; the accuracy was adequate (92 %, R2 0.52). CONCLUSION: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated.

Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases by cohort-wide immunophenotyping.

OBJECTIVE: Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases (AIRDs) is essential towards personalised medicine. METHODS: We conducted large-scale and cohort-wide immunophenotyping of 46 peripheral immune cells using Human Immunology Protocol of comprehensive 8-colour flow cytometric analysis. Dataset consisted of >1000 Japanese patients of 11 AIRDs with deep clinical information registered at the FLOW study, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In-depth clinical and immunological characterisation was conducted for the identified RA patient clusters, including associations of inborn human genetics represented by Polygenic Risk Score (PRS). RESULTS: Multimodal clustering of immunophenotypes deciphered underlying disease-cell type network in immune cell, disease and patient cluster resolutions. This provided immune cell type specificity shared or distinct across AIRDs, such as close immunological network between mixed connective tissue disease and SLE. Individual patient-level clustering dissected patients with AIRD into several clusters with different immunological features. Of these, RA-like or SLE-like clusters were exclusively dominant, showing immunological differentiation between RA and SLE across AIRDs. In-depth clinical analysis of RA revealed that such patient clusters differentially defined clinical heterogeneity in disease activity and treatment responses, such as treatment resistance in patients with RA with SLE-like immunophenotypes. PRS based on RA case-control and within-case stratified genome-wide association studies were associated with clinical and immunological characteristics. This pointed immune cell type implicated in disease biology such as dendritic cells for RA-interstitial lung disease. CONCLUSION: Cohort-wide and cross-disease immunophenotyping elucidate clinically heterogeneous patient subtypes existing within single disease in immune cell type-specific manner.

Breast Cancer Resistance Protein Limits Fetal Transfer of Tadalafil in Mice.

Tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, is a candidate therapeutic agent for fetal growth restriction and hypertensive disorders of pregnancy. In this study, we elucidated the fetal transfer of tadalafil in comparison with that of sildenafil, the first PDE5 inhibitor to be approved. We also examined the contributions of multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) to fetal transfer. Tadalafil or sildenafil was administered to wild-type, Mdr1a/b-double-knockout or Bcrp-knockout pregnant mice by continuous infusion from gestational day (GD) 14.5 to 17.5, and the fetal-to-maternal plasma concentration ratio of unbound drug (unbound F/M ratio) was evaluated at GD 17.5. The values of unbound F/M ratio of tadalafil and sildenafil in wild-type mice were 0.80 and 1.6, respectively. The unbound F/M ratio of tadalafil was increased to 1.1 and 1.7 in Mdr1a/b-knockout and Bcrp-knockout mice, respectively, while the corresponding values for sildenafil were equal to or less than that in wild-type mice, respectively. A transcellular transport study revealed that basal-to-apical transport of both tadalafil and sildenafil was significantly higher than transport in the opposite direction in MDCKII-BCRP cells. Our research reveals that tadalafil is a newly identified substrate of human and mouse BCRP, and it appears that the fetal transfer of tadalafil is, at least in part, attributed to the involvement of BCRP within the placental processes in mice. The transfer of sildenafil to the fetus was not significantly constrained by BCRP, even though sildenafil was indeed a substantial substrate for BCRP.

Comparison on removal performance of virus, antibiotic-resistant bacteria, cell-associated and cell-free antibiotic resistance genes, and indicator chemicals by ozone in the filtrated secondary effluent of a sewage treatment plant.

Due to the widespread appearance of viruses, antibiotic-resistant bacteria (ARBs), and antibiotic resistance genes (ARGs) in the aquatic environment, more powerful oxidation processes such as ozonation are needed to enhance the efficiency of their inactivation and removal during wastewater treatment. However, information is lacking on the elimination rates of viruses, ARBs, cell-associated ARGs (ca-ARGs), and cell-free ARGs (cf-ARGs) during ozonation. This study examined the kinetics and dose-dependent inactivation of a virus (MS2 coliphage) and an ARB (Ampicillin-resistant [AmpR] E. coli) and the removal of ca- and cf-ARGs (plasmid-encoded blaTEM) by ozonation in a filtered secondary effluent (SE) of a municipal sewage treatment plant (STP). In addition, the ozonation kinetics of carbamazepine (CBZ) and metoprolol (MTP)-ubiquitous organic micropollutants with different removal rate constants-were also investigated in order to monitor their effectiveness as indicators for the abovementioned biological risk factors. Our results showed that ozonation was an efficient way to remove MS2, AmpRE. coli, ARGs, CBZ, and MTP. We investigated the kinetics of their inactivation/removal with respect to exposure in terms of CT (dissolved ozone concentration C and contact time T) value, and found their inactivation/removal constants were in the following order: MS2 (8.66 ×103 M-1s-1) ≈ AmpRE. coli (8.19 ×103 M-1s-1) > cf-ARG (3.95 ×103 M-1s-1) > CBZ (3.21 ×103 M-1s-1) > ca-ARG (2.48×103 M-1s-1) > MTP (8.35 ×102 M-1s-1). In terms of specific ozone dose, > 5-log inactivation of MS2 was observed at > 0.30 mg O3/mg DOC, while > 5-log inactivation of AmpRE. coli was confirmed at 1.61-2.35 mg O3/mg DOC. Moreover, there was almost no removal of ca-ARG when the specific ozone dose was < 0.68 mg O3/mg DOC. However, 2.86-3.42-log removal of ca-ARG was observed at 1.27-1.31 mg O3/mg DOC, while 1.14-1.36-log removal of cf-ARG was confirmed at 3.60-4.30 mg O3/mg DOC. As alternative indicators, > 4-log removal of CBZ was observed at > 1.00 mg O3/mg DOC, while > 2-log removal of MTP was confirmed at > 2.00 mg O3/mg DOC. Thus, it was observed that inactivation of E. coli needs a greater ozone dose to achieve the same level of inactivation of AmpRE. coli; for ARGs, cf-ARG can persist longer than ca-ARG if low dosages of ozone are applied in the filtrated SE, CBZ might act as an indicator with which to monitor the inactivation of viruses and ARBs, while MTP might act as an indicator with which to monitor removal of ARGs. Moreover, cf-ARG cannot be neglected even after ozonation due to the possibility that ca-ARGs can become cf-ARGs during ozonation and be discharged with the final effluent, posing a potential risk to the receiving environment.

Two-dimensional phase-contrast MRI reveals changes in uterine arterial blood flow in pregnant women administered tadalafil for fetal growth restriction.

INTRODUCTION: We aimed to examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). METHODS: We recruited 14 pregnant women with FGR aged 20-44 years, at ≥20 weeks' gestation, between May 2019 and July 2020. They underwent 2D PC-MRI for UtA blood flow measurement 3 days (interquartile range: 2-4) after diagnosis. This group (FGR group) was compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received treatment with tadalafil administered at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI a week later. RESULTS: The median total UtA blood/body surface area was 420 mL/min/m2 (290-494) in the FGR group and 547 mL/min/m2 (433-681) in the control group (p = 0.01). Percent increase in blood flow were significantly different between the FGR cases treated with tadalafil and control at 15.8 % (14.3-21.3) and 4.2 % (3.6-8.7), respectively (p = 0.03). DISCUSSION: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil is expected to improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.

Preoperative Frailty Assessed Comprehensively by a Questionnaire Predicts a Poor Survival Following Curative Resection of Gastric Cancer.

Background/Aim: The concept of frailty has been attracting attention as a comprehensive indicator of the various effects of aging, but no conclusion has been reached on how to evaluate it. The present study investigated the adverse effect of preoperative frailty on short- and long-term outcomes in patients with gastric cancer using a questionnaire about frailty. Patients and Methods: One hundred and twenty-five patients with pathological stage (p Stage) I/II/III who underwent radical gastrectomy for gastric cancer at the Department of Gastroenterological Surgery, Osaka, Japan from April 2015 to December 2016 were enrolled in this study. The frailty index (FI) was calculated by dividing the total score of 50 questions consisting of 1 point per question by 50. The study used multiple logistic regression analysis with 5-year overall survival (OS) as the endpoint to create a receiver operating characteristic (ROC) curve to determine the cut-off point for the FI. The short- and long-term outcomes of the frail and non-frail groups were then compared, and prognostic factors for OS were examined. Results: Regarding the short-term outcomes, the postoperative complication rates did not differ significantly between the two groups. Regarding the 5-year OS rates of the patients with p Stages II/III, the outcomes in the frail group were significantly poorer than those in the non-frail group. In the multivariate analysis of OS, frailty was independently associated with unfavorable outcomes in patients with p Stages II/III gastric cancer. Conclusion: Frailty evaluation in this study may be useful in predicting long-term prognosis in patients undergoing surgical treatment for advanced gastric cancer.

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry.

OBJECTIVES: To determine the safety and efficacy of anifrolumab in patients with systemic lupus erythematosus (SLE) classified based on the Lupus Low Disease Activity State (LLDAS) in real-world clinical practice. METHODS: This retrospective observational study involved SLE patients who started anifrolumab therapy. The primary end point was the retention rate over 26 weeks after initiating anifrolumab therapy; 45 patients followed up for 12 weeks or longer were analyzed in the following groups to determine the safety and efficacy up to week 12 after treatment initiation: 1) non-LLDAS achievement group and 2) minor flare group. Safety and efficacy were compared between the minor flare group and the standard of care (SoC) group (treated by adding glucocorticoids (GCs) or immunosuppressants) after adjustment with inverse probability of treatment weighting using propensity score (PS-IPTW). RESULTS: The retention rate of anifrolumab was 89.7% at week 26.The LLDAS achievement rates at week 12 were 42.9% and 66.7% in the non-LLDAS achievement and minor flare groups, respectively. In both groups, GC doses and SELENA-SLEDAI score significantly decreased. When the anifrolumab group with minor flare was compared with the SoC group or the GC dose increase group, the GC dose and SLEDAI score were significantly lower in the anifrolumab group than in both groups; there was no significant difference in LLDAS achievement. CONCLUSIONS: At week 26 after initiating anifrolumab therapy, ∼90% patients remained on therapy. Anifrolumab might lower disease activity without initiating GCs and reduce GC doses, especially in patients who experience minor flares after LLDAS achievement.

Usefulness of Biopsy Specimens for Evaluating CD103+ Tumor-resident Memory T Cells in Esophageal Cancer.

BACKGROUND/AIM: CD103+ tissue-resident memory T cells (TRM) in tumor sites are associated with a favorable prognosis and predict the effectiveness of immune checkpoint inhibitors. The detection of CD103+ TRM infiltration in biopsy samples could be beneficial for patients without surgical indications. However, the usefulness of TRM detection in biopsy tissue and the difference in TRM status between biopsy and surgical specimens' post-neoadjuvant chemotherapy have not been elucidated. In the present study, we aimed to elucidate whether we can detect TRM in biopsy specimens and the impact of chemotherapy on TRM infiltration. MATERIALS AND METHODS: Tissue sections were obtained from 46 patients with esophageal cancer who received neoadjuvant chemotherapy and underwent radical esophagectomy in 2017. Immunohistochemistry was performed using an anti-CD103 antibody for biopsy and surgical specimens. We examined the relationship between CD103 expression, clinicopathological features, and prognosis for each patient. RESULTS: TRM infiltration was detected in the biopsy specimens. CD103 expression in biopsy specimens correlated with that in surgical specimens. Although there was no statistical significance in clinicopathological findings between CD103high and CD103low, patients with CD103high biopsy specimens exhibited favorable prognosis. The number of CD103+ cells was increased by chemotherapy: though with no survival benefit. CONCLUSION: Regardless of surgical indication, we were able to determine the TRM status even in biopsy specimens. CD103 evaluation at biopsy may be more useful and practical than evaluation in surgical specimens, enabling prediction of prognosis and response to immune therapy.

Effects of postural-control training with different sensory reweightings in a patient with body lateropulsion: a single-subject design study.

INTRODUCTION: Body lateropulsion (BL) is an active lateral tilt of the body during standing or walking that is thought to be affected by a lesion of the vestibulospinal tract (VST) and the subjective visual vertical (SVV) tilt. Interventions for BL have not been established. OBJECTIVE: We examined the effects of postural-control training with different sensory reweighting on standing postural control in a patient with BL. METHODS: The patient had BL to the left when standing or walking due to a left-side medullary and cerebellar infarct. This study was a single-subject A-B design with follow-up: Phase A was postural-control training with visual feedback; phase B provided reweighting plantar somatosensory information. Postural control, VST excitability, and SVV were measured. RESULTS: At baseline and phase A, the patient could not stand with eyes-closed on a rubber mat, but became able to stand in phase B. The mediolateral center of pressure (COP) position did not change significantly, but the COP velocity decreased significantly during phase B and the follow-up on the firm surface. VST excitability was lower on the BL versus the non-BL side, and the SVV deviated to the right throughout the study. CONCLUSION: Postural-control training with reweighting somatosensory information might improve postural control in a patient with BL.