Search

The introduction of biologic therapies and a treat-to-target approach has transformed the management of rheumatoid arthritis (RA), which has led to improved outcomes for women with RA who wish to become pregnant. However, guidelines for the management of reproductive health in female patients with RA are still lacking. A task force (Women of Childbearing Age [WoCBA]-Rheumatoid Arthritis in Japan) comprising 10 experts in the fields of rheumatology, obstetrics and orthopedic surgery developed 10 clinical questions (CQ) related to the management of WoCBA with RA. For each CQ, a systematic literature review was conducted to identify relevant evidence. Based on this evidence, a set of recommendations for each CQ were drafted and evaluated using the modified Delphi method. This article describes the agreed recommendations along with the supporting evidence. There are many ongoing challenges associated with the provision of reproductive healthcare in WoCBA with RA. It is hoped that the consensus-based recommendations provided here can be implemented in clinical practice in order to increase collaboration between rheumatologists and obstetricians/gynecologists and to improve reproductive health outcomes for WoCBA with RA.

An 85 year-old man was referred to our hospital because of a relapse of abscess after open surgical drainage of the right scrotum. Computed tomography (CT) showed fluid accumulation in the right scrotum and around the membranous urethra. The abscess was controlled by an open surgical drainage of the right scrotum, CT guided percutaneous drainage of the periurethral abscess and administration of antibiotics. However, the scrotal abscess recurred after 4 weeks. CT showed an enlarged abscess, and retrograde urethrography showed an urethral diverticulum extending into the scrotum associated with a scrotal abscess. Endoscopic urethral diverticulum unroofing and cautery were performed. The urinary catheter was removed 2 days after the operation. The abscess has been resolved without recurrence., 本症例の要旨は，第247回日本泌尿器科学会関西地方会にて報告した．

Background and study aims For distal malignant biliary obstruction, self-expandable metallic stents (SEMSs) have a larger inner diameter compared to plastic stents, which prolongs time to recurrent biliary obstruction (TRBO), although stent-related complications are still a problem. This study aimed to compare the outcomes between using 10– and 6-mm-diameter fully-covered SEMS (FCSEMS) for distal malignant biliary obstruction. Patients and methods This single-center, retrospective study included patients with 10-mm or 6-mm-diameter FCSEMS to treat distal malignant biliary obstruction. Clinical success, stent-related adverse events (AEs), cumulative incidence of RBO, factors involved in stent-related AEs, and factors involved in RBO were evaluated. Results There were 243 eligible cases between October 2017 and December 2021. The cumulative incidence of RBO did not differ significantly between the 10-mm and 6-mm groups. Stent-related AEs occurred in 31.6 % and 11.4 % of patients between the 10-mm and 6-mm groups, respectively (P Conclusions The 6-mm-diameter FCSEMS for distal malignant biliary obstruction is a well-balanced stent with a cumulative incidence of RBO compatible to that of the 10-mm-diameter FCSEMS and fewer stent-related AEs.

Background and study aims Recently, the utility of endoscopic ultrasound-guided intervention without fistula dilation (EUS-IV WoD) has been reported to prevent adverse events. We clinically evaluated cases in which EUS-IV WoD was attempted using a novel self-expandable metallic stent (SEMS); this is a fully covered, laser-cut SEMS that has a tapered and stiff tip specifically designed for a 0.025-inch guidewire and a relatively thin, 7F delivery system. Patients and methods We retrospectively evaluated cases wherein EUS-IV WoD was attempted using the novel SEMS between March and December 2021. Results Treatment of 11 patients by EUS-IV WoD with the novel SEMS was attempted. The technical success rate for EUS-IV was 100 % and the clinical success rate was 100 %; the success rate for EUS-IV WoD was 72.8 %. Of these, the procedural success rate for EUS-IV WoD was 100 % in EUS-biliary drainage (BD) and 57.1 % in non-EUS-BD. Early adverse events were observed in 27.3 % of patients (3/11): mild abdominal pain in two patients and moderate bleeding in one patient. The abdominal pain cases were both cases of EUS-IV WoD failure and required fistula dilation. Conclusions The novel stent may be useful for EUS-IV WoD, especially in EUS-BD.

Differences of polymer topologies affect polymer miscibility and the molecular weight dependence even with the same repeated units.

Recently, investors’ growing awareness of environmental concerns has prompted many businesses to implement green policies and procedures. Investors’ reactions to firms’ environmental efforts vary across different industries. However, few empirical studies have addressed these differences, especially in Japan – the third-largest sustainable investor in the world. Using data from Japanese food and automotive industries, this research examined sector-specific differences in investors’ reactions to firms’ environmental performance, indicated by environmentally friendly news releases, using a short-term event study and Student’s t-tests. Results indicated that investors respond negatively to environmental activities in the food and automobile sectors, supporting neo-classical theory. The data also imply that, in Japan, industry variances have a neutral effect on short-term performance but a significant long-term effect. In addition, long-term investor responses to environmentally friendly news in the food sector are more unfavorable than in the automobile industry. This study has implications for policymakers and managers.

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare disease with a poor prognosis. Because of its rarity, there is no established therapeutic regimen in unresectable cases. We report a case of PSCCT treated with weekly paclitaxel (wPTX) for more than 2 years. A 59-year-old woman presented to our hospital with a progressively enlarging neck mass. CT and MRI scans showed a tumor arising from the right lobe of the thyroid, invading the esophagus and trachea, as well as partially surrounding and invading the right common carotid artery. It was deemed unresectable. Biopsy revealed poorly differentiated squamous cell carcinoma. wPTX therapy was initiated. The patient achieved a partial response and is still undergoing treatment 28 months later. Adverse events included grade 3 neutropenia and grade 2 peripheral sensory neuropathy, which were manageable. Long-term wPTX therapy has been effective in this case of unresectable PSCCT.

Blends of multicyclic and linear polymers under biaxial elongational flow were analyzed using coarse-grained molecular dynamics simulations. The multicyclic/linear blends displayed overshoot in the normal stress difference at the start-up of biaxial elongational flow. This overshoot was steeper for multicyclic/linear blends than for our previously reported monocyclic/linear blends [T. Murashima, K. Hagita, and T. Kawakatsu, Macromolecules, 2021, 54, 7210]. Investigation of the origin of the overshoot in the multicyclic/linear blends revealed a different mechanism than that previously observed in our monocyclic/linear blends. Specifically, a "topological transition" mechanism comprising a morphological change from the open- to closed-ring state was observed in the multicyclic chains, but not in the monocyclic chains. This topological transition drastically changes the stress of the rings. Although the topological transition was also observed in asymmetric-multicyclic/linear blends, no stress overshoot appeared, owing to the asymmetry in the multicyclic chains. Therefore, we hypothesized that the structural symmetry in multicyclic chains is indispensable for overshoot behavior to occur. We determined that the topological transition in multicyclic chains with structural symmetry induces stress-overshoot behavior in multicyclic/linear blends under biaxial elongational flow., Comment: 46 pages, 13 figures

There are limited studies on the results of comprehensive genomic profiling testing for pancreatic cancer tissue specimens by endoscopic ultrasound-guided tissue acquisition (EUS-TA). This study aimed to evaluate the proportion of specimens obtained by EUS-TA using a 19-gauge (G) fine-needle biopsy (FNB) needle for unresectable pancreatic cancer (UR-PC) that met the OncoGuideIn this single-arm, prospective, phase II study, EUS-TA was performed using a 19G FNB biopsy needle in patients with suspected UR-PC based on a contrast-enhanced computed tomography scan. The primary endpoint was the proportion of patients who met the NOP analysis suitability criteria, with a threshold, expected value, α-error, and power of 40%, 70%, 0.025, and 0.9, respectively, and the planned number of enrolled patients was 33. The NOP analysis suitability criteria were defined as tumor cell content ≥ 20% and tissue size ≥ 4 mmThirty-three patients were enrolled. The procedural success rate was 100%, and the cytodiagnosis of class V was observed in all patients. The proportion of patients meeting the NOP analysis suitability criteria was 63.6% (95% CI 47.22-80.05), which satisfied the predefined criteria to be considered valid. Adverse events occurred in 9.0% of the patients.The proportion of patients with UR-PC who met the NOP analysis suitability criteria for EUS-TA using a 19G FNB needle was effective for achieving the primary endpoint, making it a valid test method. Adverse events occurred at a higher rate than that previously reported.

Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC).Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route.In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30).In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

Depression during pregnancy is relatively undertreated; however, the relationship between prenatal exposure to antidepressants and neonatal outcomes remains controversial.This retrospective cohort study used a Japanese nationwide claims database. Data of 114,359 singletons born between January 2005 and November 2019 were used to evaluate the relationship between prenatal exposure to antidepressants and neonatal morbidity.Of 2892 mothers with a history of depression before delivery, 352 (12.1%) received prescriptions within three months before delivery (MP3), and 2540 did not (non-MP3). The participants were propensity score matched (PSM) in a ratio of 1:3 using logistic regression (MP3_PSM [n = 351] vs non-MP3_PSM [n = 1052]), and maternal prescriptions of antidepressants within three months before delivery were associated with neonatal morbidity indicators, including admission to the neonatal intensive care unit (NICU) (15.7 vs. 9.1%, odds ratio (OR) 1.9 [95% confidence interval (CI): 1.3-2.6]), poor neonatal adaptation syndrome (6.0 vs 1.0%, OR 6.6 [95% CI: 3.1-14.2]), transient tachycardia (15.7 vs. 6.7%, OR 2.6 [95% CI: 1.8-3.8]), and meconium aspiration syndrome (3.1 vs 0.7%, OR 4.8 [95% CI, 1.9-12.5]). There were no significant differences in the long-term duration of stay at the NICU (15 days).Confounding factors may remain even after the propensity matching.Maternal prescription of antidepressants within three months before delivery was associated with increased admission to the NICU. However, the absolute risk of severe neonatal morbidity was low. Therefore, collaborative care for prenatal depression and the neonatal intensive care is warranted.

Immobilization osteoporosis is characterized by excess bone resorption. Vitamin D receptor activators (VDRA) might have adverse effects in immobilized patients. The objective of this study was to elucidate the impact of performance status (PS) on the associations between VDRA use and outcomes among hemodialysis patients. This is a prospective cohort study. Adults on hemodialysis in the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry were included. Exposure of interest was the use of VDRA. Outcomes were all-cause mortality and hip fracture. Associations between VDRA use and mortality or hip fractures were examined by Cox and Poisson regression analyses, respectively. Among 208,512 subjects, 128,535 were on VDRA. Poor PS was associated with higher calcium (Ca), lower parathyroid hormone, and higher alkaline phosphatase levels. The association between higher Ca levels and VDRA use was stronger among those with poor PS (p interaction 0.007). Adjusted hazard ratio (HR) (95% confidence interval [CI]) for mortality and incidence rate ratio (IRR) for hip fracture was 1.02 (95% CI, 0.99-1.05) and 0.93 (0.86-1.00) among users of VDRA, respectively. The VDRA use was associated with lower mortality and incidence of hip fractures among subjects with good PS but not among subjects with poor PS (p interaction 0.03 and 0.05). Effect modification by PS was observed for cardiovascular (CV) mortality but not for non-CV mortality. In conclusion, VDRA use was associated with better outcomes only among those with good PS. These results suggest that bone and mineral disorders among hemodialysis patients should be treated differently, depending on their performance status. © 2022 American Society for Bone and Mineral Research (ASBMR).

Aims Information on breastfeeding and the safety of biologics in infants is lacking due to difficulties in case collection. We evaluated a method for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage, and transport of breast milk. Methods To generate dried filter paper (DFP) samples, approximately 30 L of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme-linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples for stability testing, which confirmed that samples were stable up to 28 days after storage at 2–8 ºC or -20 ºC for LBM and at 25±5 ºC for DFP. LBM and DFP samples were provided by lactating mothers using biologics during lactation. Drug concentrations were compared. Results Breast milk was provided by 12 lactating mothers (tocilizumab, n=4; abatacept, n=2; etanercept, n=1; golimumab, n=1; sarilumab, n=1; and belimumab, n=3). The accuracy and precision of measurements for the six drugs were within acceptable limits. After 28 days, concentrations remained at more than 90% under all storage conditions. The quantitative values of the provided LBM and DFP samples were similar. The maximum relative infant dose ranged from 0.09% to 1.12%, which was an acceptable range. Conclusion A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women.

The electrocatalytic reduction of formate to formaldehyde with formaldehyde dehydrogenase using methylviologen redox mediated was developed.

The linear region of entropic elasticity was investigated for the regular network structure with long strands and with uniform tetra-functionality.

Background Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. Methods In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. Results Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3–31.9) and 43.8 days (26.5–61.2), respectively, mean difference (95%CI) 16.2 days (4.4–28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30–13.18) and 3.87 (1.35–11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). Conclusion c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.

Purpose Individual investors are experiencing serious sentiment shifts that influence their financial activities due to the COVID-19 pandemic while socially responsible investment (SRI) has garnered attention worldwide. This study aims to explore how individual investors’ sentiments and investment choices altered in reaction to the COVID-19 pandemic. Design/methodology/approach We surveyed 1,219 individual investors in Japan, the USA and Germany using an online questionnaire and performed a cross-sectional analysis using logit and ordered logit regressions. Findings This study found that individual investor sentiment affects SRI after COVID-19, but not necessarily in the same manner. Return-focused aspects negatively affect their SRI, while relationship-oriented social issues positively affect it. In addition, the relationship differs by nation. Japanese investors anticipate shorter term SRI returns than the US and German investors. Only Japanese investors’ SRI decisions were impacted by the relationship-oriented social factors including the environment, diversity and employee rights and welfare. Research limitations/implications This study emphasizes the need for precise motivation characterization when evaluating the same issue. The author also identified the variance and characteristics among countries, which differ from previous research. Practical implications An academically credible image of the relationship will enable business managers to find appealing strategies. This study also suggests country-specific investor relations strategies. Originality/value This study differentiates return- and relationship-oriented social motivations for SRI into 14 components, thus clarifying the relationship mechanism between the COVID-19 pandemic and individual investors’ SRI behavior. Moreover, no study has compared individual investor sentiment and investment behavior affected by the pandemic in the three countries.

Background Outcomes of a combination of peritoneal dialysis (PD) and once-weekly haemodialysis (PD + HD) have not been extensively studied. Methods This prospective cohort study using the Japanese Society for Dialysis Therapy Renal Data Registry included those who transitioned from PD to PD + HD therapy or thrice-weekly HD from 2011 to 2018. Exposure was PD + HD therapy compared with thrice-weekly HD. The outcome was time to all-cause or cause-specific death. Associations between PD + HD therapy and outcomes were examined by Cox regression. Sensitivity analyses were performed by propensity score (PS) matching, PS matching with a shared frailty model in which dialysis facilities were treated as a random effect, inverse probability weighting (IPW), PS adjustment, PS stratification, competing risk regression and on-treatment analyses in which data were censored at the transition to thrice-weekly HD for those on PD + HD therapy. Results During the study period, 1001 subjects transitioned to PD + HD therapy and 2031 to thrice-weekly HD. During a median follow-up of 3.5 years, 575 subjects died. All-cause, cardiovascular, congestive heart failure–related or infection-related mortality were not significantly different between those on PD + HD and those on thrice-weekly HD [hazard ratio 0.95 (95% confidence interval 0.78–1.16), 1.26 (0.92–1.72), 1.24 (0.77–1.99) and 0.89 (0.57–1.39), respectively]. Sensitivity analyses yielded similar results except that PD + HD therapy was associated with significantly lower all-cause mortality by PS adjustment and PS matching with the shared frailty model and lower infection-related mortality by PS adjustment and IPW. Conclusions PD + HD therapy was associated with similar or potentially lower mortality compared with thrice-weekly HD. Considering a flexible lifestyle, PD + HD therapy could be a great option.

In recent years, the range of applications of DLC coatings has been expanding, and finding the optimal additives for DLC coatings is an urgent issue. In this study, friction tests were conducted on ta-C/ta-C tribopair using a phosphonate additive with hydroxy groups, which is a combination of GMO (an additive that reduces friction of DLC) and ZDDP (an additive that reduces wear), and tribolayers after friction tests were analyzed using AFM, XPS and ToF-SIMS. The results showed that the phosphonate additive with hydroxy groups tribochemically reacted with the ta-C coating to form a low-shear, hard triblayer on the surface, thereby reducing the friction and wear of the ta-C coating.This indicates that additives with phosphonate structures and hydroxy groups are effective for DLC coatings.

Rapid effects of acupoint injection (acuinjection) at 4 acupoints (4P) (ST36, GB41, SP6, and BL60) on legs presenting sensory symptoms and motor signs in restless legs syndrome (RLS) were first described in a case report. This study aimed to confirm the beneficial effects of acuinjection.A randomized, controlled, single-blinded, prospective crossover study was conducted during 2018 to 2021. Adult volunteers (age ≥ 20 years) with RLS symptoms for 2 weeks were included. Eight adults were enrolled and randomized to receive acuinjection (Verum group) or sham injection (Sham group). The effects of acuinjection on discomfort and periodic leg movement (PLM) were evaluated using the suggested immobilization test in a crossover design. The acupoint used was 4P, and normal saline solution (0.1-0.25 mL) was injected in both groups. Leg discomfort was measured using the visual analog scale (VAS), and PLM was measured using an electromyogram. To compare the VAS scores between the groups, repeated measures analysis of variance was used, and the Student t test was used to assess the mean discomfort score (MLDS: average of the 6 VAS scores) and PLM index (PLMI) (defined as the degree of PLM/hour).A significant difference in the VAS score was observed; however, no significant difference was noted in the PLMI between the groups. The MLDS was significantly lower in the Verum group than in the Sham group.Acuinjection at 4P remarkably inhibited leg discomfort in patients with RLS. Despite the drastic PLM suppression in 1 patient by acuinjection, a statistically significant inhibition of PLM was not confirmed. The results of our study can be applied easily and safely in clinical situations where it is necessary to temporarily reduce or eliminate RLS symptoms.

BACKGROUND Oxidative stress is thought to be closely related to epileptogenesis. We have previously reported that nitric oxide (NO) levels are higher in epilepsy-prone EL mice between the ages of 3 and 8 weeks than in control mice. However, NO is divided into two fractions, nitrite (NO2) and nitrate (NO3), which appear to play different roles in epileptogenesis. METHODS NO2 and NO3 levels were measured, in EL mice and the control mice, in the parietal cortex, which is thought to be the primary epileptogenetic center in EL mice, and measured in the hippocampus, which is thought to be the secondary center. RESULTS NO3 levels in the hippocampus and parietal cortex of the immature EL mice (3 to 8 weeks of age) were significantly higher than those in the control mice; NO2 levels were significantly higher in the EL mice throughout the study period. The NO3 levels were significantly higher than the NO2 levels in the immature EL mice, but after the onset of ictogenesis at 10 weeks of age, the relative levels of the two fractions reversed. CONCLUSION The reversal of the NO fraction distribution at the onset of seizures that we observed may be related to the developmental process of seizure susceptibility in the neural network of EL mice.

Background: Trazodone is used to treat anxiety disorder, insomnia, and sleep disorders, which occur in ∼15% of pregnant and lactating women. However, pharmacokinetic information on the transfer of trazodone and its active metabolite, 1-m-chlorophenylpiperazine (mCPP), across the placenta or into breast milk is limited. In this study, we describe the pharmacokinetic profile of trazodone and mCPP concentrations in maternal and neonatal blood and breast milk. Case Presentation: A 44-year-old female received oral trazodone 50 mg once daily during pregnancy (28–38 gestational weeks) and lactation, along with etizolam for anxiety disorder with depressive syndrome. A male infant weighing 2,918 g was born at 38 weeks of gestation. Because of persistent respiratory disturbance, oxygenation was initiated immediately after birth, and the infant was admitted in the neonatal intensive care unit for 5 days. No pulmonary dysfunction or birth defects were detected, and no medication and circulatory support were needed during admission. Trazodone and mCPP concentrations in cord blood at 7.4 hours after maternal dosing were 267.6 and 22.8 ng/mL, respectively, which were comparable with maternal serum levels. The trazodone and mCPP concentrations in breast milk collected 7.2 hours after maternal dosing were 50.2 and 3.2 ng/mL, respectively. The infant developed normally, with no drug-related adverse effects at the 1-, 3-, and 6-month postpartum checkups. Conclusion: Trazodone and its active metabolite were transferred into placenta and breast milk. However, their effects in utero could not be clarified. Further studies are warranted to assess the safety of trazodone in fetuses and breastfed infants.