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In the swine industry, there is a strong need to replace an antibiotic growth promoter (AGP) used as feed additives in weaned piglets to enhance nutrient utilization in their diets and improve growth performance. Lactobacillus sakei HS-1 strain is a microbial preparation isolated from pickles. The study aim is to investigate the effectiveness of heat-treated L. sakei HS-1 strain (HT-LS) as a growth promoter in weaned piglets compared to colistin (CS), a widely used AGP. Eighteen crossbred weaned piglets (Landrace × Yorkshire × Duroc) of 21 days (average body weight [BW]: 7.06 ± 0.59 kg) were divided into three groups: fed the control diet (CT group), fed a diet supplemented with 30 ppm colistin sulphate (CS group), fed a diet supplemented with HT-LS at a concentration of 2.0 × 10 5 cells/g (LS group) until 49 days. The results indicated that LS group exhibited significantly higher average daily gain (p < 0.05) and higher BW (p < 0.1) compared with CT group, even higher than CS group. CS group showed higher growth performance compared to CT group but the differences were not statistically significant. In addition, LS group had higher (p < 0.05) or tended to higher (p < 0.1) concentrations of several plasma amino acids than the other two groups at 35 and 49 days. Faecal acetate concentration was higher (p < 0.1) in LS group than in CT group at 35 days. Blood immunoglobulin G concentration in LS group was significantly lower (p < 0.05) than in CT group at 35 and 49 days, and blood immunoglobulin A tended to be lower (p < 0.1) at 35 days than in CT group. LS group showed an increased abundance of g&#95;Prevotella 7, g&#95;Streptococcus and g&#95;Lactobacillus (linear discriminant analysis [LDA] score ≥ 2.0). Predictive metagenomic analysis revealed an enrichment of the mixed acid fermentation pathway (LDA score ≥ 2.0). Furthermore, several gut microbes exhibited correlations with plasma amino acids (p < 0.01) and short-chain fatty acids in faeces (p < 0.01). These findings demonstrate that HT-LS improves the growth performance of weaned piglets by enhancing the efficient utilization of nutrients through gut microbiota modification., (© 2024 The Author(s). Journal of Animal Physiology and Animal Nutrition published by Wiley‐VCH GmbH.)

Solitary fibrous tumor (SFT) is a spindle cell tumor driven by the NAB2-STAT6 fusion gene. While it can originate from any soft tissue, primary SFT of the pancreas is rare with limited reports. A 36-year-old man came to our department due to abdominal pain. Computed tomography revealed a circular mass with weak peripheral enhancement and an internal cyst in the pancreatic tail. Diagnosis was not confirmed through endoscopic ultrasound-guided biopsy, and differential diagnoses included acinar cell carcinoma and pancreatic neuroendocrine tumor. A robotic distal pancreatectomy with splenectomy was performed, and the patient was discharged 11 days postoperatively. Histopathological examination showed an irregular arrangement of spindle cells, and immunohistochemical staining was positive for CD34 and STAT6, confirming an SFT diagnosis with low metastatic risk. Robotic surgery effectively managed this tumor., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: The adoption of Robotic Pancreaticoduodenectomy (RPD) is increasing globally. Meanwhile, reduced-port RPD (RPRPD) remains uncommon, requiring robot-specific techniques not possible with laparoscopy. We introduce a unique RPRPD technique optimizing surgical field exposure., Methods: Our RPRPD utilizes a single-site plus-two ports technique, facilitated by a single-port platform through a 5-cm incision. The configuration of robotic arms (arm1, arm2, arm3, and arm4) were strategically designed for optimal procedural efficiency, with the arms2 and arm3, alongside the assistant trocar, mounted on the single-port platform, while the arms1 and arm4 were positioned laterally across the abdomen. Drainage was established via channels created at the arm1 and arm4 insertion sites. A "gooseneck traction" was principally employed with the robotic instrument to prop up the specimen rather than grasp, improving the surgical field's visibility and access. Clinical outcomes of patients who underwent RPRPD performed between August 2020 and September 2023 by a single surgeon across two centers in Taiwan and Japan were reviewed., Results: Fifty patients underwent RPRPD using the single-site plus-two ports technique. The gooseneck traction technique enabled goodsurgical field deployment and allowed for unrestricted movement of robotic arms with no collisions with the assistant instruments. The median operative time was 351 min (250-488 min), including 271 min (219-422 min) of console time and three minutes (2-10 min) of docking time. The median estimated blood loss was 80 mL (1-872 mL). All RPRPD procedures were successfully performed without the need for conversion to open surgery. Postoperative major morbidity (i.e., Clavien-Dindo grade ≥ IIIa) was observed in 6 (12%) patients and median postoperative hospital stay was 13 days., Conclusions: The single-site plus-two ports RPRPD with the gooseneck traction proves to be a safe, feasible option, facilitating surgical field visibility and robotic arm maneuverability., (© 2024. The Author(s).)

Background: The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality., Methods and results: We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022)., Conclusions: This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Many lifestyle-related diseases such as cancer, dementia, myocardial infarction, and stroke are known to be caused by aging, and the WHO's ICD-11 (International Classification of Diseases, 11th edition) created the code "aging-related" in 2022. In other words, aging is irreversible but aging-related diseases are reversible, so taking measures to treat them is important for health longevity and preventing other diseases. Therefore, in this study, we used BioBran containing rice kefiran as an approach to improve aging. Rice kefiran has been reported to improve the intestinal microflora, regulate the intestines, and have anti-aging effects. BioBran has also been reported to have antioxidant effects and improve liver function, and human studies have shown that it affects the diversity of the intestinal microbiota. Quantitative measures of aging that correlate with disease risk are now available through the epigenetic clock test, which examines the entire gene sequence and determines biological age based on the methylation level. Horvath's Clock is the best known of many epigenetic clock tests and was published by Steve Horvath in 2013. In this study, we examine the effect of using Horvath's Clock to improve aging and report on the results, which show a certain effect.

Competing Interests: Declaration of competing interest The authors declare no competing interests.

Background: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y 12 inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain., Methods and results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y 12 inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (P non-inferiority <0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types., Conclusions: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y 12 inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Aims: Given that fulminant myocarditis, characterized by unstable haemodynamics, is a significant clinical challenge and that traditional pharmacological treatments have limitations, evaluating alternatives such as the Impella device is a crucial focus of this study. Further, this study presents pioneering large-scale registry data on its use in managing fulminant myocarditis., Methods and Results: Data from the Japanese Registry for Percutaneous Ventricular Assist Devices (J-PVAD) were analysed to assess Impella's role in managing fulminant myocarditis from February 2020 to December 2021. The primary outcome was 30-day mortality for those treated with Impella. Of the 269 patients treated with Impella, 107 used Impella standalone, and 162 used ECPELLA (Impella combined with extracorporeal membrane oxygenation). The average age was 54 years, with 42.8% females. Overall, 74.3% survived at 30 days. Specifically, the success rate was 68.5% for the ECPELLA group and 83.2% for the Impella standalone group. Cox regression highlighted that lower estimated glomerular filtration rate and pre-Impella systolic blood pressure increased adverse event risk, while Swan-Ganz catheterization use reduced it. Adverse events were noted in 48.7% of patients, such as bleeding (32.0%) and deteriorating renal function (8.6%)., Conclusion: Impella's use in fulminant myocarditis demonstrates encouraging short-term outcomes, albeit with significant adverse events. These findings align with previous mechanical circulatory support studies, emphasizing caution regarding haemorrhagic issues. Further studies are essential to enhance patient selection and treatment approaches., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 39-year-old vegan man was admitted with diabetic ketoacidosis. He had also developed pneumonia that was unresponsive to antibiotics. Based on bronchoscopy findings, the diagnosis of Candida pneumonia was made, and the pulmonary shadow disappeared rapidly after antifungal therapy. Candida pneumonia has been mostly reported in severely immunocompromised patients. This is a rare case of Candida pneumonia that was found in a young vegan man with diabetes mellitus (DM). Although malnutrition caused by DM or an unbalanced diet is often underestimated as a cause of immunodeficiency, these conditions can be risk factors for serious opportunistic infections, including Candida pneumonia.

Background: /Objective: FOLFIRINOX therapy (FFX) for locally advanced pancreatic cancer (LAPC) is increasingly recognized as a potent neoadjuvant therapy that enables transition to conversion surgery (CS). However, predictors of CS achievement after chemotherapy are controversial. This study aimed to demonstrate the efficacy of CS after modified FFX (mFFX) in patients with LAPC and to identify and score predictors of CS., Methods: From January 2014 to December 2018, patients with LAPC who received mFFX as a first-line treatment were screened. Patients' overall survival was compared with and without CS. Moreover, the predictors for CS were analyzed to create scores for the CS factors., Results: Forty-three patients received mFFX, including 20 patients who underwent CS (CS group, 46.5%). R0 resection was achieved in 16 patients (80%). The median survival time was 39.2 months (95% confidence interval [CI] 17.3-53.8) for the CS group and 16 months (95% CI 10.5-22.6) for the non-CS group (P < 0.001; hazard ratio 0.25, 95% CI 0.12-0.54). Since an average relative dose intensity of ≥90%, tumor reduction of ≥35%, and carbohydrate antigen 19-9 reduction of ≥70% or normalization were associated with successful transition to CS in the multivariate analysis, these factors were scored (CS score, range 0-3). All of the patients in the CS group fell into the 2-3 category, compared with 2 of 23 patients in the non-CS group (P < 0.001)., Conclusion: CS after FFX contributes to the long-term survival of patients with LAPC. The CS score could be an indicator for transition to CS., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Sensitive skin is a well- known skin condition showing sensory irritation to daily used products such as cosmetics or pharmaceuticals, possibly containing sensory irritants. Methylparaben (MP), widely used as a preservative, is a representative sensory irritant and hydrolyzed in the skin. We aimed to clarify the relationship between MP sensory irritation and MP hydrolysis. First, we investigated the percutaneous penetration and hydrolysis of MP by using an ex vivo pig skin system and confirmed that topically applied MP was immediately hydrolyzed to p-hydroxybenzoic acid (PHBA). We next evaluated whether MP or PHBA causes sensory irritation using a well-used stinging test in human skin and found that MP, but not PHBA, induced irritation. Additionally, MP, but not PHBA, increased intracellular calcium in cultured TRPA1-expressed HEK293 cells, supporting the stimulatory activity of MP. Five and 10 individuals with sensitive and non-sensitive skin, respectively, were selected by a questionnaire and stinging test. In their biopsied skin samples, MP hydrolytic activity was significantly lower in sensitive than non-sensitive skin. Finally, we examined the activity of carboxylesterase (CES), which promptly hydrolyzes MP to PHBA. By using specific inhibitors of CES and CES2, we found that CES1 was responsible for MP metabolism. Our study suggests that low skin metabolism of topical agents is one of the causes of skin sensory irritation and resultant sensitive skin., (© 2023 Japanese Dermatological Association.)

Background: Transcatheter aortic valve (TAV)-in-TAV is an attractive treatment for degenerated TAV. The risk of coronary artery occlusion due to sequestration of the sinus of Valsalva (SOV) in TAV-in-TAV has been reported, but the risk in Japanese patients is unknown. This study aimed to investigate the proportion of Japanese patients who are expected to experience difficulty with the second TAV implantation (TAVI) and evaluate the possibility of reducing the risk of coronary artery occlusion. Methods and Results: Patients (n=308) with an implanted SAPIEN 3 were divided into 2 groups: a high-risk group, which included patients with a TAV-sinotubular junction (STJ) distance <2 mm and a risk plane above the STJ (n=121); and a low-risk group, which included all other patients (n=187). The preoperative SOV diameter, mean STJ diameter, and STJ height were significantly larger in the low-risk group (P<0.05). The cut-off value for predicting the risk of SOV sequestration due to TAV-in-TAV in the difference between the mean STJ diameter and area-derived annulus diameter was 3.0 mm (sensitivity 70%; specificity 68%; area under the curve 0.74). Conclusions: Japanese patients may have a higher risk for sinus sequestration caused by TAV-in-TAV. The risk of sinus sequestration should be assessed before the first TAVI in young patients who are likely to require TAV-in-TAV, and whether TAVI is the best aortic valve therapy must be carefully decided., Competing Interests: Y.M. has received educational grants from Edwards Lifesciences and lecture fees from Medtronic and Edwards Lifesciences, and is a member of Circulation Reports’ Editorial Team. T.F. serves as a consultant for Medtronic. All other authors have no relationships to disclose relevant to the contents of this article., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

A 50-year-old woman who had previously undergone right hemicolectomy and chemotherapy for colorectal cancer was hospitalized with respiratory failure. Chest computed tomography showed reticulonodular opacities and enlarged lymph nodes. A transbronchial biopsy revealed adenocarcinoma with epidermal growth factor receptor (EGFR) mutations T790M and L861Q. Treatment with the EGFR-tyrosine kinase inhibitor (TKI) osimertinib was started, and she achieved a partial response. We diagnosed her with metastatic lung tumors from colorectal cancer based on additional immunohistochemical staining and the EGFR mutation status (L861Q) of the specimens. Although cases with EGFR mutations have been rarely reported, an EGFR-TKI can be an effective treatment option for colorectal cancer.

Drug disposition after topical application to the skin has not been fully elucidated, especially after repeated application. We conducted a clinical trial to evaluate the pharmacokinetics in the stratum corneum of healthy adults after repeated application of lanoconazole cream as a model drug. We applied 25 mg of 1% lanoconazole cream onto the pre-specified areas on the participants' back once daily for 5 days. The stratum corneum was sampled twice on each study day using a standardized tape-stripping method, and the amount of lanoconazole contained in the samples was quantified using the tandem mass spectrometry method. The obtained data were used to evaluate lanoconazole pharmacokinetics in the stratum corneum. The amount of lanoconazole in the stratum corneum after once daily repeated administration reached a steady state on day 3, and it was eliminated from the stratum corneum with a half-life of approximately 11 h after discontinuing application., (© 2022 Japanese Dermatological Association.)

Introduction: Mesenchymal stromal cells (MSCs) hold the potential for application as cellular therapy products; however, there are many problems that need to be addressed before the use in clinical settings, these include the heterogeneity of MSCs, scalability in MSC production, timing and techniques for MSC administration, and engraftment efficiency and persistency of administered MSCs. In this study, problems regarding immune rejection caused by human leukocyte antigen (HLA) mismatches were addressed., Methods: Umbilical cord-derived MSCs (UC-MSCs) were gene-edited to avoid allogeneic immunity. The HLA class I expression was abrogated by the knock-out of the beta-2-microglobulin (B2M) gene; instead, the B2M-HLA-G fusion gene was knocked-in using the CRISPR/Cas9 system in combination with adeno-associated virus (AAV)., Results: Cell surface markers on gene-edited UC-MSCs were not different from those on primary UC-MSCs. The gene-edited UC-MSCs also retained the potential to differentiate into adipocytes, osteoblasts, and chondrocytes. B2M gene knock-out alone protected cells from allogeneic T cell immune responses but were vulnerable to NK cells. B2M gene knock-out in combination with B2M-HLA-G knock-in protected cells from both T cells and NK cells. The B2M-HLA-G knock-in MSCs retained a good immunosuppressive ability and the addition of these cells into the mixing lymphocyte reaction showed a significant inhibition of T cell proliferation., Conclusions: The results of this study demonstrated the possibility that the CRISPR/Cas9 system combined with AAV can be used to effectively disrupt/introduce any gene into UC-MSCs. Our findings suggest that the gene-edited cell line produced here using this method may have a higher ability to escape the cytotoxic activity of immune cells than primary cells, thereby being more advantageous for long-term graft survival., Competing Interests: RN is employed by Daiwa Pharmaceutical. SM is employed by Keijinkai Medical Corporation. AT received a research grant from Daiwa Pharmaceutical. TN-I, TO, and MF has no conflicts of interest., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

A 57-year-old man with lung adenocarcinoma was treated with chemotherapy and immune checkpoint blockade. After two cycles of carboplatin, pemetrexed, and pembrolizumab, he developed a persistent fever. Chest computed tomography (CT) suggested inflammation of the aortic wall. We treated the patient with corticosteroids. After four cycles of carboplatin, pemetrexed, and pembrolizumab, chest CT showed an aneurysm in the ascending aorta. We diagnosed him with inflammatory thoracic aortic aneurysm induced by pembrolizumab and performed surgical replacement of the ascending aorta. Although this might be a very rare case, we should be aware of aortitis as a potential adverse effect of pembrolizumab.

Rapid ventricular pacing (RVP) is commonly employed during transcatheter aortic valve replacement (TAVR); however, frequent TAVR is associated with worse prognoses. The retrograde INOUE-BALLOON ® (IB) allows balloon aortic valvuloplasty (BAV) without RVP. The aim of this study was to evaluate the feasibility of retrograde IB for TAVR preparation. The study population included 178 consecutive patients (mean age, 84 ± 5 years; male, 47%) who underwent retrograde BAV before prosthetic valve replacement via the transfemoral approach. Patients were divided into a retrograde IB group without RVP (n = 74) and a conventional balloon (CB) group with RVP (n = 104). The primary endpoint was prolonged hypotension after BAV (reduced systolic pressure < 80 mmHg for over 1 min or vasopressor drug requirement). The incidence of prolonged hypotension after BAV was significantly lower in the IB group compared with the CB group (4% vs. 16%, p = 0.011). Balloons were able to penetrate and expand the aortic valve in both groups. RVP was used less for total TAVR in the IB group compared with the CB group. The aortic valve area-index after BAV was not significantly different between the two groups (0.72 ± 0.14 cm 2 /m 2 vs. 0.71 ± 0.12 cm 2 /m 2 ; p = 0.856). Multivariate analysis demonstrated that IB use was associated with avoidance of prolonged hypotension (OR, 0.27 [0.059-0.952]; p = 0.041). In conclusion, BAV using retrograde IB without RVP is both safe and feasible. More stable hemodynamics were achieved using retrograde IB by avoiding RVP during TAVR., (© 2021. The Author(s).)