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In recirculating aquaculture systems (RAS), maintaining water quality in aquaculture tanks is a paramount factor for effective fish production. A down-flow hanging sponge (DHS) reactor, a trickling filter system used for water treatment of RAS that employs sponges to retain biomass, has high nitrification activity. However, nitrification in seawater RAS requires a long start-up time owing to the high salinity stress. Therefore, this study aimed to evaluate the nitrification characteristics and changes in the microbial community during the conversion of freshwater to seawater in a DHSreactor fed with ammonia-based artificial seawater. The total ammonia nitrogen concentration reached 1.0 mg-N·L -1 (initial concentration 10 mg-N·L -1 ) within 11 days of operation, and nitrate production was observed. The 16 S rRNA gene sequence of the DHS-retained sludge indicated that the detection rate of the ammonia-oxidizing archaeon Candidatus Nitrosocosmicus decreased from 23.9 % to 14.0 % and 25.8-17.6 % in the upper and lower parts of the DHS reactor, respectively, after the introduction of seawater. In contrast, the nitrite-oxidizing bacteria Nitrospira spp. increased from 0.1 % to 9.5 % and from 0.5 % to 10.5 %, respectively. The ammonia oxidation rates of 0.12 ± 0.064 and 0.051 ± 0.0043 mg-N·g-MLVSS -1 ·h -1 on the 37th day in the upper and bottom layers, respectively. Thus, nitrification in the DHS reactor performed well, even under high-salinity conditions with short operational days. This finding makes the transition from freshwater to saltwater fish in the RAS system simple and economical, and has the potential for early start-up of the RAS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takahiro Watari reports financial support was provided by Japan Society for the Promotion of Science. Takahiro Watari reports financial support was provided by Japan Science and Technology Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The 15th Japan Bioanalysis Forum (JBF) Symposium was held in Kyoto, Japan, between 5 and 7 February 2024. The conference theme, 'Toward the new world - Science as a universal endeavor' indicated that universal discussion based on science is making a basis of regulatory and analytical sciences, now internationally harmonized. The symposium discussed a wide range of topics, including ICH M10, quantitative PCR, immunogenicity, peptide LC-MS, e-notebooks, artificial intelligence, reliability standards, carrier development, inviting domestic and overseas experts. Approximately 360 attendees from various fields, including pharmaceutical companies, contract research organizations, academia and regulators, gathered in person or online.

Biological molecules incorporating trifluoromethyl ketones (TFMKs) have emerged as reversible covalent inhibitors, aiding in the management and treatment of inflammatory diseases, cancer, and respiratory conditions. TFMKs, renowned for their versatile binding properties and adaptability, are pivotal in the rational design of novel drugs for diverse diseases. The photocatalytic insertion of alkenes, abundant feedstocks, into the α-carbon of trifluoromethylacetone represents a highly effective and atom-economical method for synthesizing valuable TFMKs. However, these processes typically necessitate high-energy photoirradiation ( λ > 300 nm, Hg lamp) and stoichiometric oxidants to generate the acetonyl radical from acetone. In our study, we demonstrate the visible-light photocatalytic radical addition into olefins using bromotrifluoroacetone as the trifluoroacetonyl radical precursor under mild conditions. Aliphatic trifluoromethyl ketones or the corresponding bromo-substituted products can be obtained by selecting an appropriate photocatalyst and solvent. Comprehensive experimental investigations, including cyclic voltammetry, Stern-Volmer quenching studies, and kinetic isotope effects, corroborate the synthesis of trifluoroacetonyl radical species from bromotrifluoroacetone under photoredox conditions. Further, we demonstrate the efficient synthesis of an oseltamivir derivative bearing a trifluoromethylketone moiety, which shows promising biological activity. Hence, this methodology will streamline the direct introduction of trifluoromethyl ketone into biological target molecules during drug discovery.

Aquaponics is a promising solution for addressing food security concerns. Nonetheless, an effective water-purification system is necessary to achieve high and stable yields of fish and vegetables. This study aimed to evaluate the nitrification and oxygen transfer performance of a laboratory-scale down-flow hanging sponge (DHS) reactor with a Brassica oleracea aquaponics system to treat water in an Oreochromis niloticus closed-aquaculture system. The DHS reactor showed a higher oxygen transfer coefficient ( K L a) than the conventional aerator and provided an adequate dissolved oxygen (DO) concentration of approximately 5.5 mg/L essential for O. niloticus growth throughout the experimental period. The evaluated DHS-based aquaponic system maintained high water quality in an aquaculture tank, with a survival rate of 97%. The O. niloticus grew at a low feed conversion ratio of 1.5-2.1 and a low feeding rate of 0.5% at high stocking densities of 17.5-22.2 kg-fish-weight/m 3 . 16S rRNA gene sequencing indicated that the DHS sponge carrier effectively retained nitrifying bacteria such as Nitrosomonas and Nitrospira . This study demonstrated that the DHS reactor provided a high DO concentration and that a simultaneous DHS reactor with a hydroponic tank provided a low-cost aquaponic system that could be applied for food production in the aquaculture industry.

Background: Dyspnea and desaturation during exercise are essential assessment items for pulmonary rehabilitation. Characterizing patients using these 2 factors may be important for providing more effective pulmonary rehabilitation. This study aimed to categorize subjects with interstitial lung disease (ILD) using dyspnea and desaturation at the end of the 6-min walk test (6MWT)., Methods: This was a retrospective study including 230 stable subjects with ILD who underwent 6MWT in our out-patient department at a general hospital in Japan. The modified Borg scale and oxygen saturation determined by S pO 2 at the end of the 6MWT were used for cluster analysis using the k -means method with k = 4., Results: Subjects were classified into 4 characteristic clusters. S pO 2 at the end of the 6MWT was lower in cluster 4 (80.5 ± 3.0%) than in clusters 1 (94.3 ± 2.0%), 2 (94.3 ± 1.9%), and 3 (87.9 ± 1.8%) and was lower in cluster 3 than in clusters 1 and 2. The modified Borg scale score at the end of the 6MWT was higher in clusters 2 (4 [3-8]), 3 (3 [0-9]), and 4 (4 [0-7]) than in cluster 1 (0.5 [0-2.0]) and was higher in cluster 2 than in cluster 3., Conclusions: Subjects with ILD were classified into 4 characteristic clusters using dyspnea and S pO 2 at the end of the 6MWT. The 4 clusters are characterized as follows: Cluster 1 had mild desaturation and mild dyspnea; cluster 2 had mild desaturation and severe dyspnea; cluster 3 had both moderate desaturation and dyspnea, and cluster 4 had both severe desaturation and dyspnea. These classification data offer insight for individualized pulmonary rehabilitation for patients with ILD., (Copyright © 2024 by Daedalus Enterprises.)

Purpose: Taxanes are widely used chemotherapeutic agents that frequently cause nail changes and have a significant impact on patients' quality of life. Despite the prevalence of taxane-induced nail toxicity, limited data are available regarding evidence-based management strategies for the prevention or treatment of taxane-induced nail changes. Therefore, we aimed to gain insights into the prevention, treatment, and evaluation of nail changes in patients with cancer in Japan by conducting a questionnaire survey of physicians, pharmacists, and nurses involved in oncology treatment., Methods: The questions addressed prophylactic methods, evaluation practices, and treatment approaches for various nail disorders. The questionnaires were distributed on March 1, 2022, with a response deadline of December 1, 2022., Results: Of the 120 questionnaires distributed, 88 (73.3%) were returned, and all of them were analyzed. The respondents included 69 physicians (32 oncologists, 26 breast surgeons, 6 dermatologists, 3 obstetricians/gynecologists, 1 gastroenterological surgeon, and 1 urologist), 9 pharmacists, and 10 nurses. Prophylactic measures included moisturizing (58.0%), protection (42.0%), cooling therapy (37.5%), and cleanliness (33.0%). Approximately 70% of the respondents used the Common Criteria for Adverse Events (CTCAE), while approximately 30% did not use a specific evaluation method. Opinions regarding treatment with antimicrobial or corticosteroid ointments varied; however, all severe cases were referred by dermatologists., Conclusion: Our survey revealed that the management of chemotherapy-induced nail changes varies in clinical practice in Japan. These findings emphasize the need for standardized management strategies and further research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It is difficult to evaluate adequate dose of heparin for cardiopulmonary bypass (CPB) by activated clotting time (ACT) in a patient receiving both heparin and dabigatran because dabigatran can also prolong ACT. We evaluated the effect of dabigatran by thromboelastography (TEG) to determine adequate heparin dose for CPB., Case Presentation: An 81-year-old woman receiving both heparin and dabigatran was scheduled for an emergency surgical repair of iatrogenic atrial septal perforation. Although ACT was prolonged to 419 s, we performed TEG to distinguish anticoagulation by dabigatran from heparin comparing R in CK and CHK. As the results of TEG indicated residual effect of dabigatran, we reversed dabigatran by idarucizumab and then dosed 200 U/kg of heparin to achieve adequate anticoagulation for CPB by heparin., Conclusions: TEG could help physicians to determine need for idarucizumab and also an adequate dose of heparin to establish appropriate anticoagulation for CPB., (© 2024. The Author(s).)

Therapeutic oligonucleotides such as antisense oligonucleotide (ASO) and small interfering RNA (siRNA) are among the most remarkable modalities in modern medicine. ASOs and siRNA are composed of single- or double-stranded 15-25 mer synthesized oligonucleotides, which can be used to modulate gene expression. Liquid chromatography-mass spectrometry (LC/MS) is a necessary technique for the quality control of therapeutic oligonucleotides; it is used to evaluate the quantities of target oligonucleotides and their impurities. The widely applied oligonucleotide therapeutic quantitation method uses both ultraviolet (UV) absorbance and the MS signal intensity. Peaks separated from the main peak, which contains full-length product, are generally quantitated by UV. However, coeluting impurities, such as n - 1 shortmers, abasic oligonucleotides, and PS → PO (phosphorothiate to phosphodiester) oligonucleotides, are quantitated by MS. These coeluting impurities can also be comprised of various isomers with the same modification, thus increasing the difficulty in their separation and relative quantitation by LC/MS. It is possible that a specific isomer with a certain structural form induces toxicities. Therefore, characterization of each isomer separation is in high demand. In this study, we separated and characterized oligonucleotide isomers by employing a cyclic ion mobility mass spectrometry (cyclic IMS) system, which allows the separation of ions with the same m / z ratio based on their structural differences. Patisiran antisense and sense strands and their n - 1 and abasic isomers were used as sample sequences, and their ratio characterization was achieved by cyclic IMS. In addition, we evaluated the PS → PO conversion isomers of the antisense strand of givosiran, which originally contained four PS modification sites. The PS → PO isomers exhibited specific and distinguishable mobiligram patterns. We believe that cyclic IMS is a promising method for evaluating therapeutic oligonucleotide isomers.

Objective: In this retrospective case-control study, we aimed to evaluate the nasopharyngeal airway volume of children with Down syndrome (DS) and compare the results with those of control participants well matched for sex and age., Materials and Methods: Fifteen children with DS (mean age = 9.43 ± 0.38 years; 8 boys, 7 girls) and 15 control participants (mean age = 9.51 ± 0.40 years; 8 boys, 7 girls) were enrolled. The nasopharyngeal airway volume and the cross-sectional morphology were measured with cone-beam computed tomography taken for orthodontic treatment. All measurements were assessed by analysis of covariance (ANCOVA) using Bonferroni post hoc pairwise comparison tests. Covariates were body height and body weight, and the ANB angle and the mandibular plane angle. Significance was set at P < .0019., Results: Nasal airway, superior airway, and total airway volumes of DS participants were significantly smaller than those of the control participants in ANCOVA results adjusted for ANB angle and mandibular plane angle (P = .000). In ANCOVA results adjusted for body height and body weight, no statistically significant differences in the volume measurements were found., Conclusion: The results indicate that the nasopharyngeal airway volume differs between children with and without DS and that the airway volume tends to be smaller in DS children than in children without DS., (© 0000 by The EH Angle Education and Research Foundation, Inc.)

Sialyl glycans have several biological functions. We have previously reported on the preparation and bifidogenic activity of milk-derived sialylglycopeptide (MSGP) concentrate containing sialyl O -glycans. The current study qualitatively and quantitatively analyzed the sialyl O -glycans present in the MSGP concentrate. Notably, our quantitative analysis indicated that a majority of O -glycopeptides in the MSGP concentrate were derived from glycomacropeptides. The concentrate was found to contain mainly three types of sialyl core 1 O -glycans, with the disialyl core 1 O -glycan being the most abundant. We successfully quantified three types of sialyl core 1 O -glycans using a meticulous method that used homogeneous O -glycopeptides as calibration standards. Our results provide valuable insights into assessment strategies for the quality control of O -glycans in dietary products and underscore the potential applications of MSGP concentrate in the food industry and other industries.

Spleen tyrosine kinase (Syk), a non-receptor-type tyrosine kinase, has a wide range of physiological functions. A possible role of Syk in Alzheimer's disease (AD) has been proposed. We evaluated the localization of Syk in the brains of patients with AD and control participants. Human neuroblastoma M1C cells harboring wild-type tau (4R0N) were used with the tetracycline off (TetOff) induction system. In this model of neuronal tauopathy, the effects of the Syk inhibitors-BAY 61-3606 and R406-on tau phosphorylation and oligomerization were explored using several phosphorylated tau-specific antibodies and an oligomeric tau antibody, and the effects of these Syk inhibitors on autophagy were examined using western blot analyses. Moreover, the effects of the Syk inhibitor R406 were evaluated in vivo using wild-type mice. In AD brains, Syk and phosphorylated tau colocalized in the cytosol. In M1C cells, Syk protein (72 kDa) was detected using western blot analysis. Syk inhibitors decreased the expression levels of several tau phosphoepitopes including PHF-1, CP13, AT180, and AT270. Syk inhibitors also decreased the levels of caspase-cleaved tau (TauC3), a pathological tau form. Syk inhibitors increased inactivated glycogen synthase kinase 3β expression and decreased active p38 mitogen-activated protein kinase expression and demethylated protein phosphatase 2 A levels, indicating that Syk inhibitors inactivate tau kinases and activate tau phosphatases. Syk inhibitors also activated autophagy, as indicated by increased LC3II and decreased p62 levels. In vivo, the Syk inhibitor R406 decreased phosphorylated tau levels in wild-type mice. These findings suggest that Syk inhibitors offer novel therapeutic strategies for tauopathies, including AD., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD., Methods: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports., Results: During a median follow-up period of 70.5 months (3-120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer., Conclusion: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP., Methods: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients)., Results: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery., Conclusions: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use., Methods: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis., Results: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes., Conclusions: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Phylogenetic analysis based on single-nucleotide polymorphism (SNP)-based through whole-genome sequencing is recognized as the standard method for probing nosocomial transmission. However, the application of WGS is constrained by the high cost of equipment and the need for diverse analysis tools, which limits its widespread use in clinical laboratory settings. In Japan, the prevalent use of PCR-based open reading frame typing (POT) for tracing methicillin-resistant Staphylococcus aureus (MRSA) transmission routes is attributed to its simplicity and ease of use. Although POT's discriminatory power is considered insufficient for nosocomial transmission analysis, conclusive data supporting this notion is lacking. This study assessed the discriminatory capabilities of SNP analysis and POT across 64 clinical MRSA strains. All 21 MRSA strains of ST5/SCCmec IIa, having more than 16 SNPs, demonstrated distinct clones. Conversely, two strains shared the same POT number and were identified as group A. Among the 12 MRSA strains of ST8/SCCmec IVl with over nine SNPs, five fell into POT group B, and five into POT group C. All four MRSA strains of ST8/SCCmec IVa were classified into POT group D, although they included strains with more than 30 SNPs. Among the 27 MRSA strains of ST1/SCCmec IVa, 14 were classified into POT group E. However, except for two clusters (each comprising two or three strains), all had SNP counts >10 (Fig. 1-D). SNP analysis of MRSA in CC1/SCCmec IV showed that several strains had the same number of SNPs in POT number (106-183-37), even among bacteria with >100 SNPs, indicating POT's limited use in detailed nosocomial transmission analysis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

A 44-year-old HIV-positive man diagnosed with diffuse large B-cell lymphoma in 2021 achieved complete remission with six cycles of R-CHOP therapy but had a relapse in November 2022. ESHAP therapy failed to induce remission, leading to complete remission with four cycles of Pola-BR therapy. Post-failure of autologous stem cell harvest, cord blood transplantation (CBT) was performed in June 2023. Notably, this case used recently approved intramuscular antiretroviral therapy (ART) with cabotegravir and rilpivirine, addressing gastrointestinal complications during CBT. This innovative use of intramuscular ART in the treatment of malignancy represents a first in the field, offering a pioneering approach to HIV-related lymphoma., Competing Interests: Declarations of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A down-flow hanging sponge (DHS) reactor is a trickling filter system used for wastewater treatment, which employs sponges to retain biomass. This study assessed the process performance of a compact DHS combined with a sedimentation tank with seven phases at varying hydraulic retention times (HRT) over 500 days. The BOD of the DHS effluent was maintained at 4.0 ± 0.5 mg·L -1 for the shortest HRT 0.3 ± 0.1 h. The nitrification efficiency was considerably impacted by the reduced HRT, with NH 4 + -N and NO 3 - -N concentrations of 9.0 ± 1.2 mgN·L -1 and 2.2 ± 0.5 mgN·L -1 , respectively. Nevertheless, the effluent complied with effluent discharge standards throughout the trial period. The number of comammox 16S rRNA gene copies ranged from 5.58 to 13.2 × 10 7 copies·mL -1 , indicating that sponges biomass retained carrier can provide favorable conditions for comammox growth and could contribute to nitrification in the high-rate DHS reactor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study evaluated the risk of metachronous colorectal cancer (CRC) after resection of index (first) rectal cancer in patients with Lynch syndrome (LS)., Methods: Clinicopathological data of patients with genetically proven LS were retrospectively analyzed in this multicenter Japanese study. The cumulative incidence of metachronous CRC and the overall survival were compared between patients with index rectal cancer (rectal group) and those with index colon cancer (colon group)., Results: The median age at index CRC surgery was lower in the rectal group than in the colon group (37 vs. 46 years old, P = 0.01). The cumulative 5-, 10-, and 20-year incidences of metachronous CRC were 3.5%, 13.9%, and 21.1%, respectively, in the rectal cancer group and 14.9%, 22.0%, and 57.9%, respectively, in the colon cancer group (P = 0.02). The overall survival curves were not significantly different between two groups (P = 0.23)., Conclusion: This is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS., (© 2024. The Author(s).)

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range., (© 2024. The Author(s).)

A novel bio-carrier, PVA/Fe/starch gel bead, was fabricated and developed to enhance the anaerobic treatment performance of synthetic azo dye-containing wastewater. PVA-gel beads with 5 % magnetite and 0.5 % starch were optimal for physical strength and treatment performance. A pair of 2 L-up-flow anaerobic sludge blankets (UASB), one with the bead (UB) and another without (U) as a controller, operated continuously at 30 °C and an HRT of 11-24 h for 302 days. UB showed better performance than U in most phases, especially with influent dye of 200 mg·L -1 , suggesting a greater tolerance to dye toxicity of UB than U. Microbial analysis revealed that the PVA/Fe/starch gel beads successfully captured the dye degrader Clostridium. Diversity indices indicated that PVA/Fe/Starch gel beads effectively support microbial diversity and resilience under varying dye concentrations. Overall, these findings demonstrate the potential of PVA/Fe/Starch gel beads to improve the stability and efficiency of the dye treatment system., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takahiro Watari reports financial support was provided by Japan Society for the Promotion of Science. Takahiro Watari reports financial support was provided by Kurita Water and Environment Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients in whom endoscopic submucosal dissection (ESD) has resulted in noncurative resection need further surgical treatment. However, the oncologic outcome of additional gastrectomy after ESD compared with surgery alone remains unclear., Methods: The clinical data of 778 patients who underwent gastrectomy for early gastric cancer (EGC) from January 2008 to December 2019 in Ishikawa Prefectural Central Hospital were retrospectively analyzed. Of these 778 patients, 187 underwent additional gastrectomy after ESD [ESD (+) group] and 591 underwent surgery alone [ESD (-) group]. We compared the overall survival and disease-free survival between the ESD (+) and ESD (-) groups, using propensity score matching (PSM) to adjust for baseline characteristics. We also assessed early postoperative outcomes., Results: After PSM based on sex (male or female), age, tumor diameter, tumor gross type, and operative procedure, each group comprised 144 patients with no significant differences in clinical background characteristics. After matching, the 5-year overall survival rate in the ESD (+) and ESD (-) group was 90.9% and 87.8%, respectively, with no significant difference (P = .470). In addition, there was no significant difference in the disease-free survival rate (97.6% vs 95.8%, respectively; P = .504). The postoperative complication rate was similar in both groups., Conclusion: Additional gastrectomy for patients in whom ESD resulted in noncurative resection did not adversely affect the long-term prognosis. Additional gastrectomy after ESD is oncologically acceptable for EGC., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR), prevalent in acute heart failure (AHF), has a poor prognosis; however, the dynamics of TR severity during hospitalization and its prognostic implications remain unclear. We investigated TR dynamism during hospitalization and its prognostic impact in AHF., Methods and Results: This is a post hoc analysis of a prospective multicenter study of patients with AHF who underwent echocardiographic TR severity evaluation at admission and before discharge. The primary endpoint was a combined of 1-year all-cause mortality and heart failure rehospitalization after discharge. Among 1079 participants, TR severity changed dynamically, with 60.3% of those with moderate TR and 29.6% of those with severe TR at admission were diagnosed as no/mild TR at discharge. In three groups stratified by changes in TR severity, the persistent TR groups had higher incidence of primary endpoint than the resolution and absence groups. In adjusted analyses, the persistent group (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.04-1.80), but not the resolution group (HR, 1.07; 95% CI, 0.79-1.44), had higher primary endpoint incidence than the absence group., Conclusions: TR severity at admission in patients with AHF can change dynamically and is associated with subsequent prognosis. Significant TR that remains even after decongestive therapy might be a target for further treatment in hospitalized patients with AHF., Competing Interests: Declaration of competing interest Y.M. received honoraria from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. T.O. received lecture fees from Ono Yakuhin, Novartis, Otsuka, Boehringer Ingelheim, AstraZeneca, and Pfizer as well as research grants from Ono Yakuhin, Pfizer, Alnylam, and Alexion (unrelated to the submitted work). K.K. received honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceutical Co., Ltd. Other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

In a membrane bioreactor (MBR) system, in situ sludge reduction techniques induce membrane fouling. To address this challenge, we incorporated a rotating mesh carrier, which can adsorb organic matter and provide a habitat for metazoans, into the anoxic tank of a conventional anoxic/oxic-MBR (A/O-MBR) system, termed rotating biological contactor-MBR (RBC-MBR), and evaluated treatment performance. Over 151 days, lab-scale RBC-MBR and A/O-MBR were used to treat municipal sewage. Both reactors showed similar COD and NH 4 + removal rates. However, RBC-MBR reduced excess sludge by approximately 45 % compared with A/O-MBR. Microscopic observation and 18S rRNA gene-based microbial analysis revealed the persistence of microfauna and metazoans (oligochaetes, nematodes, and rotifers) in RBC, which are typically absent in activated sludge. Additionally, the metazoan's population in the RBC-MBR membrane tank was two-fold that of A/O-MBR, indicating enhanced sludge reduction through predation. Despite these reductions, the increase in transmembrane pressure was similar between RBC-MBR and A/O-MBR, suggesting that sludge holding by RBC mesh media degrade fouling substances, such as proteins and polysaccharides and improves sludge filterability, resulting in membrane fouling mitigation. Microbial communities in both reactors were similar, indicating that the installation of RBC did not alter the microbial community of sludge. Network analysis suggested potential symbiotic or prey-predator relationships between bacteria and metazoans. This study reveals that RBC-MBR effectively reduced the excess sludge while mitigating membrane fouling, highlighting one of the promising technology for applying metazoan predation into MBR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Although treatment outcomes for metastatic colorectal cancer (mCRC) have dramatically improved over the past few decades, drug costs have also significantly increased. This study aimed to investigate which first-line treatment regimens for mCRC are actually used (frequency) in Japanese practice and at what cost., Methods: We collected data on patients with mCRC who received first-line treatment at 37 institutions of the Japan Clinical Oncology Group Colorectal Cancer Study Group from July 2021 to June 2022, and calculated the cost of regimens. The cost per month of each regimen was estimated based on standard usage, assuming a patient with a weight of 70 kg and a body surface area of 1.8 m2. We categorized the regimens into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month), and others (<500 000 JPY/month)., Results: The study included 1880 participants, 24% of whom were ≥ 75 years. Molecular targeted containing regimens were received by 78% of the patients. The most frequently used regimen was the doublet regimen (fluoropyrimidine with either oxaliplatin or irinotecan) plus bevacizumab (43%), followed by doublet plus cetuximab or panitumumab (21%). The cost of molecular targeted drugs-containing regimens (ranging from 85 406 to 843 602 JPY/month) is much higher than that of only cytotoxic drug regimens (ranging from 17 672 to 51 004 JPY/month). About 16% received high-cost treatments that included panitumumab-containing regimens and pembrolizumab (17% of patients aged ≤74 years and 11% of patients aged ≥75 years)., Conclusion: About 16% of mCRC patients received first-line treatment with regimens costing >500 000JPY/month, and molecular targeted drugs being the main drivers of cost., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: The role of the zinc fingers and homeoboxes family (ZHX1-3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues., Methods: Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (n = 33), hepatitis C (n = 16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (n = 5). Next-generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan-Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors., Results: High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus-associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation-negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation-positive HCC and HCC patients over 70 years old., Conclusions: These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC., (© 2024 Japan Society of Hepatology.)

Background: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety., Methods: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil., Results: Out of 104 patients who met the criteria, the median age was 58 years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed., Conclusion: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: Lateral pelvic lymph node (LPLN) metastasis of rectal neuroendocrine tumors (NETs) is rare, with unknown oncological features. We investigated the oncological impact of LPLN metastasis in patients with rectal NETs., Methods: This study included 214 patients with rectal NETs who underwent curative surgery. We evaluated their clinicopathological characteristics and short- and long-term outcomes., Results: LPLN dissection was performed in 15 patients with LPLN swelling ≥ 7 mm (preoperative imaging); 12 patients had LPLN metastases, 6 of whom had LPLN metastases without mesorectal lymph node metastases (skip metastasis). The short-term outcomes were similar between the groups with and without LPLN dissection. The median follow-up period was 59.4 months, and patients with LPLN metastasis showed significantly shorter disease-free and overall survival rates than those without metastasis. Among 199 patients who did not undergo LPLN dissection, only 1 had LPLN recurrence. In a univariate analysis, tumor depth, tumor grade, and LPLN metastasis were associated with the overall survival. In the multivariate analysis, only LPLN metastasis was an independent predictor of the overall survival., Conclusions: LPLN metastasis is a poor prognostic factor for patients with rectal NETs. LPLN enlargement can be considered an indication for dissection, owing to its high rate of metastasis and associated poor prognosis., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Treating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab., Case Presentation: A 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis., Conclusions: The WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer., (© 2024. The Author(s).)

Three thienopyrrole-fused thiadiazole (TPT) fluorescent dyes featuring a common amide linker and different alkoxy substituents on peripheral trialkoxybenzene moieties were synthesized, and their self-assembly behavior in solution was investigated. The obtained results revealed a substantial steric effect of the alkoxy substituents on the supramolecular polymerization mechanism, which results from a combination of π-stacking and hydrogen (H)-bonding interactions. Detailed spectroscopic measurements revealed that with increasing steric demand of the substituents, the supramolecular polymerization processes in pure methylcyclohexane (MCH) or a mixture of MCH and toluene become temperature-sensitive and enthalpically favorable, resulting in a change from the isodesmic assembly mechanism to the cooperative mechanism. Theoretical calculations suggested that in TPTs with bulky substituents, steric hindrance causes the H-bonding array of the amide moieties to be aligned along the stacking axis of the π-systems; thus, the H-bonding interactions are strengthened compared to those in TPTs with less bulky substituents, compensating for the weakened π-stacking interactions. A chiral TPT derivative with (S) stereogenic centers was found to form homochiral helical supramolecular assemblies that generate discernible circularly polarized luminescence. Achiral TPTs also generate helical assemblies to which preferential helicity can be imparted through the external chiral bias of the solvents (R)- and (S)-limonene., (© 2024 Wiley‐VCH GmbH.)

In multi-mass systems, torsional vibration is a common and annoying phenomenon. Effective vibration suppression and robustness to wide-range parameter variations are essential for a sound motion system. However, most control methods focus on the primary resonance mode, and the high-order resonance modes are not actively treated in the control design, resulting in the control bandwidth not being high enough and limiting the control performance. This paper proposes a novel two-stage design scheme to realize a wideband control to improve control performance. First, a hybrid uncertainty model is tailored for multi-mass systems, which uses an equivalent and uncertain spring constant to describe the variation of the primary mode and a dynamic uncertainty to cover the other resonance modes. This hybrid model strikes a better balance between the model conservatism and the feasibility of a less conservative design. Then, the passivity of the parameter uncertainty is utilized to conduct a phase compensation on the nominal system. After the phase compensation, all uncertainties are converted into norm-bounded ones, and the robust performance design is carried out. This method is applied to vehicle drivetrain benches, and its superiority is validated through simulation comparisons and experiments on two typical types of drivetrain benches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society of Automation. Published by Elsevier Ltd. All rights reserved.)

Background: Needlescopic surgery is a minimally invasive procedure that uses thin trocars with 3-mm diameter. We used Turnbull-Cutait pull-through and delayed coloanal anastomosis in needlescopic surgery to avoid diverting ileostomy during intersphincteric resection for low rectal cancer. In this study, we aim to assess the diverting ileostomy avoidance rate and technical safety of this "minimal skin incision and no stoma" procedure., Methods: This single-center retrospective study was conducted at the Cancer Institute Hospital, a tertiary referral center in Japan. Between January 2017 and December 2020, 11 patients underwent needlescopic intersphincteric resection with diverting ileostomy (NSI group), and 19 patients underwent needlescopic intersphincteric resection with delayed coloanal anastomosis (NSD group) for low rectal cancer. Data regarding patient backgrounds and short-term outcomes, including diverting ileostomy avoidance rate, pathological results, and postoperative defecatory function, were compared between the groups., Results: There were no statistically significant differences between the NSI and NSD groups with respect to patient background, operation time (239 min versus 220 min, p = 0.68), estimated blood loss (45 g versus 25 g, p = 0.29), R0 resection rate (100% versus 100%, p = 1.00), and length of postoperative hospital stay (16 days versus 17 days, p = 0.42). The diverting ileostomy avoidance rate was 94.4% in the NSD group. The LARS and Wexner scores 12 months after surgery were not significantly different between the two groups., Conclusions: Needlescopic intersphincteric resection and delayed coloanal anastomosis can be safely performed in selected patients with a high rate of diverting ileostomy avoidance and comparable short-term outcomes., (© 2024. Springer Nature Switzerland AG.)

Two types of cross-linked polymeric dye films that exhibit reversible color changes in response to pH were prepared. Upon protonation, films with a nitrophenol dye moiety (NP) changed from yellow to colorless, whereas films with an azobenzene dye moiety (AB) changed from yellow to reddish-purple. The colored light transmitted through these films from a D65 white-light source was measured colorimetrically, and the transition of the chromaticity point in CIELAB upon protonation of the polymeric dyes was observed. At low dye concentrations ([NP] < 4.7 × 10 -5 and [AB] < 2.7 × 10 -5 mol L -1 ), linear loci of the chromaticity points were displayed for both polymeric dye films, indicating perceptual linearity. This linearity is caused by the avoidance of nonlinear perceptual phenomena such as the Abney effect and the Bezold-Brücke phenomenon. The perceptual linearity of space is a necessary condition for achieving stoichiometric linearity, which requires an additional linear relationship between the dye concentration and each component, a *, b *, and L *. A geometric equation that included the AB concentration and the protonation ratio of AB was used to successfully depict, on the basis of stoichiometric linearity, the protonation of the polymeric AB films three-dimensionally in the restricted area of CIELAB., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Acute lung injury (ALI) is caused by a variety of illnesses, including aspiration pneumonia and sepsis. The CCR4-NOT complex is a large multimeric protein complex that degrades mRNA through poly(A) tail shortening, whereas it also contributes to regulation of transcription and translation. Cnot3 is a scaffold component of the CCR4-NOT complex and is essential for the integrity of the complex; loss of Cnot3 leads to depletion of whole complex. While the significance of cytokine mRNA degradation in limiting inflammation has been established, the roles of CCR4-NOT complex-mediated in ALI remain elusive., Methods: The effects of Cnot3 haploinsufficiency in the pathology and cytokine expression were analyzed in the mouse lungs of acid aspiration-induced acute lung injury. The decay rate and transcription activity of cytokine mRNAs under Cnot3 heterozygous deletion were analyzed in lipopolysaccharide (LPS) -stimulated mouse embryonic fibroblasts (MEFs)., Results: Tamoxifen-induced heterozygous deletion of Cnot3 in adult mice (Cnot3 Hetz) did not show body weight loss or any apparent abnormality. Under acid aspiration-induced acute lung injury, Cnot3 Hetz mice exhibited increased pulmonary edema, worse lung pathologies and more severe inflammation compared with wild type mice. mRNA expression of pro-inflammatory genes Il1b and Nos2 were significantly upregulated in the lungs of Cnot3 Hetz mice. Consistently, mRNA expression of Il1b and Nos2 was upregulated in LPS-stimulated Cnot3 Hetz MEFs. Mechanistically, while heterozygous depletion of Cnot3 stabilized both Il1b and Nos2 mRNAs, the nascent pre-mRNA level of Il1b was upregulated in Cnot3 Hetz MEFs, implicating Cnot3-mediated transcriptional repression of Il1b expression in addition to destabilization of Il1b and Nos2 mRNAs. PU.1 (Spi1) was identified as a causative transcription factor to promote Il1b expression under Cnot3 haploinsufficient conditions., Conclusion: CNOT3 plays a protective role in ALI by suppressing expression of pro-inflammatory genes Il1b and Nos2 through both post-transcriptional and transcriptional mechanisms, including mRNA stability control of Spi1., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yamaguchi et al.)

Objectives: Residual dissection is a concern in endovascular treatment with a DCB, and there is limited knowledge of hemodynamics at a dissection lesion. Therefore, the objective of this study is to evaluate the mean pressure gradient (MPG) and fractional flow reserve (FFR) at a residual dissection after DCB angioplasty for the superficial femoral artery (SFA)., Methods: A total of 59 cases with residual SFA dissection treated with DCB angioplasty at a single center were analyzed retrospectively. The dissection was classified into 6 types (A-F). The primary endpoints were MPG and FFR at a residual dissection lesion after DCB angioplasty, using evaluation with a pressure wire., Results: The median lesion length was 70 (40-130) mm with 24% popliteal involvement, and 11 cases (18%) had chronic total occlusion. A completion angiogram revealed dissection of types A (n = 33, 56%), B (n = 18, 31%), C (n = 7, 12%), and D (n = 1, 2%). The median MPGs in type A, B, and C cases were 0 (0-2), 0 (0-4), and 3 (0-6) mmHg, with a significant lower in type C cases than in type A cases (A vs C, P = .021). The median FFRs in type A, B, and C cases of 1.0 (.98-1.00), 1.0 (.96-1.00), and .98 (.95-1.00) did not differ significantly among dissection types (A vs B, P = .86; A vs C, P = .055; B vs C, P = .15)., Conclusions: This is the first report of hemodynamics at a SFA dissection. The results suggest that low-grade dissection (types A or B) does not affect MPG and FFR at a SFA lesion. This indicates that a bailout stent may be unnecessary for patients with dissection of types A or B. A further investigation is needed to determine whether a scaffold is required for a SFA lesion with type C dissection., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The concept of non-mass abnormalities of the breast has been employed in Japan for approximately 20 years. Although B-mode findings are classified as non-mass abnormalities, the usefulness of adding color Doppler ultrasonography (US) and strain elastography to B-mode US is unclear. Therefore, we conducted a multicenter study (JABTS BC-07) to establish the diagnostic criteria for breast US, including color Doppler and elastography, for non-mass abnormalities of the breast and verify their diagnostic usefulness., Methods: We registered US images of non-mass abnormalities of the breast and their clinical and histopathological data from 13 institutions (202 malignant and 183 benign non-mass lesions). Furthermore, we evaluated the centralized image interpretation usefulness of the diagnostic criteria for B-mode and color Doppler US, as well as the sensitivity and specificity when color Doppler US and elastography were added to B-mode US., Results: Echogenic foci in the mammary gland (odds ratio 3.45, 95% confidence interval [CI] 1.92-6.19, p < 0.0001) and the configuration of internal solid components of the ducts (odds ratio 0.056, 95% CI 0.005-0.591, p < 0.0165) significantly differentiated benign and malignant non-mass abnormalities. The sensitivity of B-mode alone (83.7%) was significantly improved by adding color Doppler US (93.1%) (p = 0.0004); however, adding color Doppler US and elastography to B-mode US made no significant difference in either sensitivity or specificity., Conclusion: Although adding color Doppler US and elastography to B-mode US improved sensitivity, the diagnostic significance was limited. Therefore, a comprehensive diagnostic method comprising mammography and magnetic resonance imaging is warranted., (© 2024. The Author(s).)

The proportion of cerebral venous sinus thrombosis involving the straight sinus (StS) is low, and the prognosis is poor. We report a case of multiple sinus thrombosis involving StS in which the patient underwent mechanical thrombectomy (MT) using a stent retriever and an aspiration catheter (combined MT) with a good postoperative course. A 15-year-old girl was admitted to our hospital with rapid loss of consciousness. Magnetic resonance imaging (MRI) revealed thrombosis of the bilateral internal cerebral veins, vein of Galen, StS, torcular herophili (TH), and right transverse sinus (TS), as well as edema mainly in the left thalamus, basal ganglia, and corpus callosum. Systemic heparinization was initiated, and combined MT was performed. Although complete recanalization of the TH and right TS via the left internal jugular vein was achieved, the microwire could not be advanced to the StS. Hence, the approach route was changed to remove the thrombus from the superior sagittal sinus and successfully reach the StS via the right TS. Partial recanalization of the StS was achieved, and venous congestion was improved. Two months after MT, the patient returned to school without neurological deficits. MRI performed 3 months after MT revealed disappearance of the edema and complete recanalization of the StS. In this case, StS catheterization via the left TS was not possible. However, we could reach the right TS, which were recanalized first. Partial recanalization of the StS can be expected a good prognosis under the patency of the TH and TS., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Japan Neurosurgical Society.)

Anterior cruciate ligament (ACL) injury is a concerning problem in the paediatric population, impacting joint health and longevity. Moreover, ACL injury hampers physical activity, which is important for children's social network and general well-being. Recent data demonstrates a rise in paediatric ACL reconstructions, affecting both girls and boys. However, it is unclear whether this rise reflects a higher injury rate or a more proactive approach towards surgery, as information on nonoperated patients is lacking. Regarding gender differences, increasing evidence implies that girls engaged in pivoting sports experience a higher incidence of ACL injuries and reinjuries compared to boys. Furthermore, data suggest that girls have inferior outcomes and lower return-to-sport rates than boys. The social context in which girls compete in sports is likely a significant contributing factor to the risk of serious knee injuries. Lack of attention and insufficient data on gender-based differences in ACL injuries, outcomes and evidence-based treatment guidelines highlight the need for further research on this topic. LEVEL OF EVIDENCE: Level IV., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background and Objectives: Ruptured aneurysms visualized by vessel wall MRI (VW-MRI) exhibit characteristic aneurysm wall enhancement (AWE). A secondary bulge of the aneurysmal wall, called a bleb, is often the site of rupture in ruptured aneurysms. We hypothesized that a higher degree of AWE would identify the rupture point in aneurysms with multiple blebs., Methods: AWE was quantitatively analyzed in consecutive ruptured intracranial aneurysms with multiple blebs (31 aneurysms with a total of 72 blebs) using VW-MRI. A 3-dimensional T1-weighted fast spin-echo sequence was obtained after contrast media injection, and the contrast ratio of the aneurysm wall against the pituitary stalk (CRstalk) was calculated as the AWE indicator. Bleb characteristics, including CRstalk and wall shear stress (WSS), were compared between ruptured and unruptured blebs. Odds ratios with 95% confidence intervals for ruptures were calculated by conditional logistic regression analysis., Results: Ruptured blebs had a higher CRstalk and lower WSS compared with unruptured blebs. CRstalk remained significantly associated with the bleb rupture status in the conditional logistic regression (adjusted odds ratio 3.9, 95% CIs 1.6-9.7)., Conclusion: AWE is associated with the bleb rupture status independent of WSS. Contrast-enhanced VW-MRI may be a useful noninvasive tool for identifying the rupture point and guiding the treatment strategy., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

The WHO recently proposed a new indicator for judging the appropriateness of antimicrobial selection according to the AWaRe classification. Although macrolides are often administered for long-term macrolide therapy, the impact of this therapy on the indicator remains unclear. This study examined the impact of this therapy on the indicator for outpatient oral antimicrobial use. Using the JMDC claims database, outpatients who were prescribed an oral antimicrobial at least once between January and December 2022 (n = 2.66 million) were included in the study. The ratio of patient numbers and antimicrobial usage (AMU) were calculated based on age group (<15, 15-64, and ≥65 years) and prescription days (1-15, 16-30, 31-60, 61-90, and ≥91 days), and AMU of each drug was corrected for defined daily doses and classified according to the AWaRe. Patients with chronic airway disease for whom macrolides were prescribed for 91 days and more were defined as long-term macrolide therapy. Macrolides accounted for more than 30 % of total oral AMU in all age groups. In the elderly, 11.2 % of patients were prescribed macrolides for 91 days or more, accounting for 66.4 % of macrolide use. With regard to diseases that were associated with macrolide prescriptions, the percentage of patients prescribed for chronic airway diseases increased as the number of days of prescription increased. These results suggest that the impact of long-term macrolide therapy should be considered when assessing the appropriateness of outpatient oral AMU according to the AWaRe classification., Competing Interests: Declarations of interest All authors have no conflicts of interest to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children., Methods: Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00-12:00) and PM (17:00-21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS)., Results: Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020)., Conclusions: SalC correlated with pain. Caregiver attendance effectively alleviated stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study., Design: This study was a prospective birth cohort study., Setting: This study population included 104 059 fetal records who participated in The Japan Environment and Children's Study from 2011 to 2014., Participants: Pregnant women whose children had undergone developmental testing were included in this analysis., Primary and Secondary Outcome Measures: Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development., Results: Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers., Conclusion: An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis., Materials and Methods: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities., Results: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively., Conclusion: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daichi Fujimoto reported receiving grants and personal fees from AstraZeneca KK and Boehringer Ingelheim Japan Inc. and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD KK, Eli Lilly Japan K.K., Kyowa Kirin, Daiichi Sankyo, and Novartis Pharma KK outside the submitted work. Hidetoshi Hayashi reported receiving grants from PAREXEL International Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., SYNEOS HEALTH CLINICAL K.K., Covance Japan Inc., Sanofi K.K., Novartis Pharma K.K., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., Eisai Co., Ltd., Japan Clinical Research Operations, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Sysmex Corporation, Takeda Pharmaceutical Co., Ltd., IQVIA Services JAPAN K.K., GlaxoSmithKline K.K., EPS Corporation, Medical Research Support, PRA Health Science, Inc., Eisai., Inc., Nippon Boehringer Ingelheim Co., Ltd., and PPD-SNBL K.K. and personal fees from AstraZeneca K.K., Bristol Myers Squibb Company, Amgen, Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., and Pfizer Japan Inc outside the submitted work. Yukihiro Toi reported receiving personal fees from Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer, Inc., and Kyowa Kirin Co., Ltd., outside the submitted work. Toshihide Yokoyama reported receiving personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc, Bristol-Myers Squibb Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., MSD, Novartis, and Merck Biopharma Co., Ltd. outside the submitted work. Terufumi Kato reported receiving grants from Abbvie, Amgen, AstraZeneca, BeiGene, BluePrint, Chugai, Daiichi-Sankyo, Eli Lilly, Haihe, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, Takeda, and TurningPoint and personal fees from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda outside the submitted work, and his wife is an employee of Eli Lilly. Teppei Yamaguchi reported receiving personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Bristol-Meyers Squibb, and Novartis outside the submitted work. Kaoru Tanaka reported receiving personal fees from AstraZeneca, Merck Biopharma, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Novartis Pharma outside the submitted work. Satoru Miura reported receiving personal fees from AstraZeneca KK, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan Inc, Eli Lilly Japan K.K., Novartis Pharma K.K., Pfizer, Kyowa Hakko Kirin, Daiichi Sankyo, Abbive, Nippon Kayaku, AMGEN, Merck, and Takeda Pharmaceutical Co., Ltd. outside the submitted work. Motohiro Tamiya reported receiving personal fees from Pfizer, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, and Amgen outside the submitted work. Motoko Tachihara reported receiving grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and Eli Lilly Japan Co., Ltd., and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., MSD K.K., Novartis pharmaceuticals K.K., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo, Pfizer Japan, Inc., and Janssen Pharmaceutical K.K. Takehito Shukuya reported receiving grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Novartis, and MSD and personal fees from Taiho Pharma, Daiichi-Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Kayaku, Pfizer, Takeda Pharmaceutical Co., Ltd., and Eli Lilly outside the submitted work. Yuko Tsuchiya-Kawano reported receiving personal fees from Bristol-Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, MSD, and Ono Pharmaceutical outside the submitted work. Yuki Sato reported receiving personal fees from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Kyowa Kirin, and Boehringer Ingelheim outside the submitted work. Satoshi Ikeda reported receiving personal fees from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Daiichi-Sankyo, and Pfizer outside the submitted work. Shinya Sakata reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Takeshi Masuda reported receiving personal fees from MSD K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Kyowa Kirin outside the submitted work. Isamu Okamoto reported receiving personal fees from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca Plc., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd., and Novartis Pharma K.K. outside the submitted work. Nobuyuki Yamamoto reported receiving grants from AstraZeneca K.K., MSD K.K., Amgen Astellas BioPharma, Eisai Co., Ltd., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Janssen Pharmaceutical K.K., Amgen K.K., Taiho Pharmaceutical Co., Ltd., Toppan USA, Inc., Nippon Boehringer Ingelheim Co., Ltd., and Daiichi Sankyo Co., Ltd. and personal fees from MSD K.K., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Merck Biopharma Co., Ltd., outside the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal interval of colonoscopy (CS) surveillance in cases with Lynch syndrome (LS), and stratification according to the causative mismatch repair gene mutation, has received much attention. To verify a feasible and effective CS surveillance strategy, we investigated the colorectal cancer (CRC) incidence at different intervals and the characteristics of precancerous colorectal lesions of LS cases., Methods: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path&#95;) were analyzed according to the data of 1,756 registered CS., Results: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path&#95;MLH1, path&#95;MSH2, and path&#95;MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path&#95;MSH6 cases as compared with that for path&#95;MLH1 and path&#95;MSH2 cases., Conclusions: In cases with path&#95;MLH1, path&#95;MSH2, and path&#95;MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path&#95;MSH6 cases could be stratified with path&#95;MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset., (© 2024. Japanese Society of Gastroenterology.)

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Extracellular vesicles (EVs) serve as an intrinsic system for delivering functional molecules within our body, playing significant roles in diverse physiological phenomena and diseases. Both native and engineered EVs are currently the subject of extensive research as promising therapeutics and drug delivery systems, primarily due to their remarkable attributes, such as targeting capabilities, biocompatibility, and low immunogenicity and mutagenicity. Nevertheless, their clinical application is still a long way off owing to multiple limitations. In this context, the Science Board of the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan has conducted a comprehensive assessment to identify the current issues related to the quality and safety of EV-based therapeutic products. Furthermore, we have presented several examples of the state-of-the-art methodologies employed in EV manufacturing, along with guidelines for critical processes, such as production, purification, characterization, quality evaluation and control, safety assessment, and clinical development and evaluation of EV-based therapeutics. These endeavors aim to facilitate the clinical application of EVs and pave the way for their transformative impact in healthcare., (© 2024. The Author(s).)

A 32-year-old man, who was treated for T-cell lymphoma, presented in cardiac arrest. He had been treated for heart failure with reduced ejection fraction. Veno-arterial extracorporeal membrane oxygenation was initiated immediately. We diagnosed him as non-ST elevated myocardial infarction. Coronary angiography demonstrated the occlusion of the trifurcation in the proximal left anterior descending artery (LAD). We failed to advance the first guidewire into the distal LAD by angio-based conventional wiring. Intravascular ultrasonography (IVUS) of the proximal diagonal branch revealed two diaphragms separating the distal lumen without connection, which looks like lotus root-like appearance. We quickly penetrated the plaque using IVUS-based real-time 3D wiring using the tip detection method. The contrast injection via the microcatheter showed the distal diagonal branch (D2). After the balloon dilation in D2, IVUS image revealed a torn plaque between D2 and the distal LAD. Subsequently we advanced the guidewire to the distal LAD using IVUS-based real-time 3D wiring using the tip detection method through the tear of the plaque. Finally, we successfully performed the revascularization of LAD in a preferable procedure time. The patient recovered well and was discharged 39 days after cardiac arrest. This case highlights the efficacy of IVUS-based real-time 3D wiring using the tip detection method even in the emergent and challenging situation., (© 2024 Wiley Periodicals LLC.)

Purpose: The aim of this study was to investigate the incidence and clinical features of immunologic rejection after deep anterior lamellar keratoplasty (DALK)., Methods: This study included 411 patients (464 eyes, median age [interquartile range; IQR] 55.8 years [36.1-69.5]) who underwent DALK at Tokyo Dental College between June 1997 and 2021. Of 411 patients, 24 (24 eyes [5.2%], 51.9 years [IQR 31.6-65.4]) developed immunologic rejection. We characterized the clinical features, risk factors associated with immunologic rejection, and prognosis., Results: The interval between DALK and immunologic rejection was 14.5 (range, 5-78) months. Immunologic rejection occurred after cessation/reduction of topical steroid in 9 (47.4%) and suture removal in 4 eyes (21.1%). The postoperative duration of topical steroid use in eyes with immunologic rejection was significantly shorter (10.0 months, [IQR 6.0-14.0]) than those without immunologic rejection (28.3 [IQR 15.8-42.7], P = 0.001). Immunologic rejection manifested as stromal edema in 19 (100.0%), ciliary hyperemia in 17 (89.5%), keratic precipitates in 13 (68.4%), epithelial edema in 13 (68.4%), infiltration in 9 (47.4%), corneal opacity in 4 (21.1%), and Descemet membrane detachment in 2 eyes (10.5%). After treatment, corneal clarity was restored in 17 eyes (89.5%); however, immunologic rejection led to corneal endothelial decompensation in 2 eyes (10.5%). Endothelial cell density decreased from 1795.7 ± 722.6 to 1651.6 ± 655.6 cells/mm 2 after immunologic rejection ( P = 0.074)., Conclusions: Post-DALK immunologic rejection was associated with specific clinical triggers such as reduction/cessation of topical steroids or suture removal., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)