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OBJECTIVE: Wound repair dysfunction is becoming a major public health issue worldwide. Yes-associated protein (YAP) has previously been reported to be closely related to wound healing, while how YAP accelerates wound healing via regulating autophagy needs to be further probed. MATERIALS AND METHODS: ICR male mice were involved in two independent animal experiments; the mice were randomly allocated into control, autophagy inhibitor (3-MA) (injection), and 3-MA (drip) group or control, si-NC, si-YAP group (8 mice for each). Full-thickness excisional wounds (8 mm) in mice were created by punch to construct an in vivo wound model to observe the effects of autophagy inhibitor (3-MA) (by injection and drip) and si-YAP by electrotransfection. RESULTS: Firstly, we found that the autophagy inhibitor (3-MA) accelerated wound closure in vivo. Loss-of-function experiments subsequently revealed that YAP knockdown led to increased proliferation and migration of fibroblasts as well as reduced autophagy, resulting in accelerated wound healing. In addition, our results revealed that YAP could positively regulate Engrailed-1 (En1) expression in fibroblasts. En1 knockdown also promoted the proliferation and migration of fibroblasts, meanwhile resulting in increased mammalian target of rapamycin (mTOR) levels and reduced autophagy in fibroblasts. CONCLUSIONS: YAP knockdown repressed autophagy in fibroblasts to accelerate wound closure by regulating the En1/mTOR axis. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 64-year-old man who was found to have a pancreatic head mass during a follow-up for colon cancer. The mass was confirmed to be a solid pseudopapillary neoplasm (SPN) through a biopsy. The tumor had invaded the main pancreatic duct and showed high-grade malignant transformation. Metastases developed in the para-aortic lymph nodes and liver one year after surgery. The article highlights the importance of careful treatment for patients with SPN suspected of having high-grade malignant transformation. [Extracted from the article]

In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated β-galactosidase activity and proliferation marker bromodeoxyuridine. RRM2B upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: In Japan, gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy are the standard treatments for locally advanced gastric cancer. Neoadjuvant chemotherapy (NAC) is not affected by postgastrectomy syndromes or postoperative complications. This multicenter retrospective study investigated the prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer who underwent NAC followed by gastrectomy., Methods: Consecutive patients (n = 221) with advanced gastric cancer who underwent NAC followed by curative surgery were enrolled in this study. Prognostic factors including postoperative adjuvant chemotherapy were investigated using univariate and multivariate analyses., Results: A multivariate analysis revealed that pathological lymph node metastasis (ypN) status and postoperative adjuvant chemotherapy were independent prognostic factors for the overall and relapse-free survival. Forty-five patients (20.4%) did not receive postoperative adjuvant chemotherapy. There were no significant differences between patients with and without adjuvant chemotherapy for all factors, except age. The most common reason for not undergoing postoperative adjuvant chemotherapy was a poor condition (n = 23)., Conclusions: ypN status and postoperative adjuvant chemotherapy were independent prognostic factors in gastric cancer patients who underwent NAC followed by curative gastrectomy. It is important to maintain the patient's condition during NAC and the perioperative period so that they can receive postoperative adjuvant chemotherapy., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: We compared the effects of growth hormone (GH) treatment on height and predicted adult height in children with short stature born small for gestational age (SGA-SS) vs. with a growth hormone deficiency (GHD)., Methods: This retrospective study analyzed the background and clinical characteristics of children who presented to Tanaka Growth Clinic for short stature and were diagnosed with either SGA-SS or GHD and underwent treatment with GH. We compared differences in height, height velocity, GH dose increases, insulin-like growth factor-1 levels, and bone-age/chronological-age ratio between the two groups., Results: Out of these children, 33 SGA-SS and 54 GHD children started GH treatment before the age of 8 years, with a mean dose of 0.25 mg/kg/week and 0.20 mg/kg/week, respectively. At treatment initiation, the age and height standard deviation scores (SDS) of the SGA-SS group were significantly lower than those of the GHD group. The height velocity was significantly greater in the SGA-SS group for 3 years owing to higher GH doses and younger age. No notable differences in puberty onset height or predicted adult height were observed between the two groups for boys or girls. The increase in height SDS from the start of GH treatment until the onset of puberty was substantially greater in the SGA-SS group than in the GHD group for both sexes., Conclusions: Adult height of patients with SGA-SS is expected to resemble that of patients with GHD but may not reach the -1.0 SD achieved with GH treatment of those patients in Western countries., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: PCI for aorto-ostial CTO remains challenging. The techniques for guidewire in aorto-ostial CTO may differ from those used in non-aorto-ostial CTOs, influenced by clinical and angiographic characteristics., Objectives: This study aimed to assess the technical aspects and outcomes of percutaneous coronary intervention (PCI) in patients with aorto-ostial chronic total occlusion (CTO)., Methods: This analysis included 420 patients with ostial CTO from the Japanese CTO-PCI Expert Registry, spanning January 2014 to December 2022. It examined the strategies and procedural outcomes of CTO PCI., Results: Ostial CTO represented 420 of 10,814 (3.9%) of all CTO PCI cases. Within this subset, aorto-ostial CTO accounted for 218 of 420 (52%) cases. The technical success rate for aorto-ostial CTO was 88% (191/218). Aorto-ostial CTOs exhibited longer lesion lengths and were more likely to present with challenges such as distal target lumen ambiguity, calcification, and tortuosity compared with non-aorto-ostial CTOs. The retrograde approach was more commonly used in aorto-ostial CTO, with retrograde direct crossing being the most successful technique, especially in cases of flush CTO. A multivariate logistic analysis identified several factors significantly associated with unsuccessful aorto-ostial CTO PCI, including difficulties in engaging a guiding catheter, estimating the collateral channel (as assessed by the J-Channel score), and tortuosity., Conclusions: Aorto-ostial CTOs are more complex and frequently require a retrograde approach. The availability of suitable interventional collateral channels is crucial for the success of these procedures., Competing Interests: Funding Support and Author Disclosures Dr Tsuchikane has served as a consultant for Asahi Intecc, Boston Scientific Japan, and Kaneka. Dr Ito has received speaker honorarium from Boston Scientific Japan, Abbott Medical Japan, TERUMO, and Medtronic Japan. Dr Oikawa has received speaker honorarium from Abbott Medical Japan, Boston Scientific Japan, Medtronic Japan, Nipro, TERUMO, Kaneka, and OrbusNeich Medical. Dr Yoshikawa has received speaker honorarium from TERUMO, Abbott Medical Japan, Kaneka, Nipro, and OrbusNeich Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: This study evaluated the effectiveness of a pocket-sized ultrasound device in preoperative planning for lymphaticovenular anastomosis (LVA) to enhance lymphedema treatment outcomes., Methods: A retrospective analysis was performed on 24 patients who underwent LVA for secondary upper extremity lymphedema between June 2020 and August 2022. Patients were categorized into two groups: the ultrasound group, which used a pocket-sized device (Vscan Air), for preoperative vein identification, and a control group that did not. Preoperative lymphatic mapping was performed using indocyanine green lymphography, and suitable veins for anastomosis were identified using ultrasound. Upper extremity lymphedema index and incision length were compared., Results: Participants in the ultrasound group had a shorter average incision length (2.85 ± 0.48 cm) than those in the control group (3.23 ± 0.78 cm, p = 0.038), indicating a more targeted and minimally invasive approach. Although volume reduction rates were not significantly different, the pocket ultrasound device facilitated more precise vein selection, enhancing surgical planning., Conclusion: Pocket-sized ultrasound devices provide a cost-effective and practical solution for vein identification during LVA, particularly in resource-limited settings. While high-frequency ultrasound offers superior resolution, portable devices could become standard tools for lymphatic surgery with continued technological advancement., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

The medial thigh, rich in lymphatic vessels, presents risks of seroma and lymphoedema after flap elevation. This study discusses a novel approach using indocyanine green (ICG) to preserve lymphatic vessels while harvesting a descending genicular artery perforator (DGAP) flap for knee reconstruction. Here, we present the case of a 44-year-old woman who developed a skin defect below the right knee after cellulitis and abscess debridement. Preoperative ICG lymphography identified the lymphatic pathways, allowing for a meticulous flap design to avoid vessel damage. The surgery resulted in successful flap integration and a full range of knee motion without complications. Follow-up ICG lymphography confirmed the preservation of the lymphatic vessels. This case underscores the importance of lymphatic preservation in medial thigh flap procedures to minimise postoperative complications, such as seroma, cellulitis, and transient lymphoedema. Further research is required to explore the applications of this technique in broader clinical settings., Competing Interests: None., (© 2024 The Author(s).)

Senescent cells accumulate with age and contribute to age-related diseases and organ dysfunctions. Early evidence suggests that removal of senescent cells using senolytic drugs improves the aging phenotype in mice and may improve the health of individuals with chronic diseases. Signs of skin aging, including wrinkles, and sagging, occur largely due to the accumulation of senescent fibroblasts within the dermis; However, there is currently no skin treatment that eliminates senescent cells. In this study, human fibroblasts subjected to replicative aging and ionizing radiation exposure are used to screen plant extracts for potential senescent cell-destructive and/or senescent cell-forming activities. Angelica acutiloba-a traditional Chinese herbal medicine-selectively kills senescent cells without affecting the proliferating cells. Among the major components of this herb, ligustilide shows promising senescent cell-destructive properties, and selectively eliminates senescent cells by inducing an apoptosis. Moreover, ligustilide markedly inhibits senescence-associated secretory phenotypes. Administration of ligustilide to mouse skin eliminates senescent cells and increases dermal collagen density and subcutaneous adipose tissue content; it selectively promotes death of senescent cells without affecting non-senescent cells. These results provide evidence that a natural compound-ligustilide-may exhibit therapeutic effects on the skin aging phenotype by specifically inducing apoptosis in senescent cells., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Acquired choanal atresia is a rare complication of pharyngeal surgical interventions. Here, we report the case of a 72-year-old woman who was treated in our institution for acquired choanal atresia after failed previous treatments. We have excised the obstructing fibrotic scar tissue and then reconstructed the area using a mucosal local flap and free radial forearm flap transfer. Choanal stenosis caused by abnormal granulation was identified in the months after surgery; however, this was treated with endoscopic dilatation and steroid injections in the outpatient setting. No restenosis was identified 1 year after the operation. Postoperative evaluation of speech was satisfactory. Free flap transfer could be an option for refractory choanal atresia, and endoscopic dilatation with local steroid injections may be an effective method to treat postoperative restenosis., 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.

Background and Objectives: Lymphaticovenular anastomosis (LVA) is a surgical technique used to alleviate lymphedema by bypassing the lymphatic and venous vessels and facilitating lymphatic fluid drainage. Accurate evaluation of anastomotic patency is crucial for assessing LVA outcomes. Traditional near-infrared fluorescence lymphography has limitations, including fluorescence diffusion in subcutaneous fat and difficulty evaluating areas beneath the dermal backflow. Photoacoustic imaging (PAI) is a potential alternative for high-resolution visualization of lymphatic and blood vessels. We aimed to evaluate the utility of PAI for assessing LVA patency., Methods: Using the LUB0 PAI system, we examined patients who underwent LVA. Imaging was conducted using subcutaneously injected indocyanine green (ICG) to visualize lymphatic vessels., Results: Results showed clear patency in some cases, inability to evaluate it in others, and confirmed occlusion in certain instances., Conclusions: While PAI provides valuable insights, challenges remain, including the potential for ambiguous results from the intermittent nature of lymphatic flow and difficulty visualizing low-ICG-concentration lymphatic vessels. Nonetheless, PAI offers a promising method for detailed 3D evaluation of anastomoses. It may improve surgical outcomes and contribute to future evidence in the field. Further advancements, including real-time video assessment, may enhance the accuracy and reliability of LVA patency evaluation., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Amikacin  liposome inhalation suspension (ALIS) improved sputum culture conversion rate at 6 months for patients with refractory Mycobacterium avium complex pulmonary disease (MAC-PD) in an international phase 3 trial. Patient characteristics and chest high-resolution CT (HRCT) findings associated with ALIS effectiveness are poorly documented., Objective: We aimed to clarify ALIS effectiveness for refractory MAC-PD at 6 months, elucidating associated patient characteristics and chest CT findings., Methods: We reviewed medical records of 12 patients with refractory MAC-PD for whom ALIS treatment was initiated at Toho University Omori Medical Center from November 2021 through September 2022. All patients demonstrated treatment persistence for at least 3 months. They were divided into culture conversion and non-conversion groups using sputum culture conversion status after 6-month ALIS treatment initiation. Clinical and radiological characteristics were compared., Results: Seven of the 12 patients (58.3%) achieved sputum culture conversion within 6 months. The culture conversion group had shorter pre-ALIS initiation treatment duration [21 months (16-25) vs. 62 months (32-69); p = 0.045]; lower cavitary lesion incidence on HRCT (28.6% vs. 100%; p = 0.028); and fewer clarithromycin (CLA)-resistant strains [0/7 (0%) vs. 3/5 (60%); p = 0.045]. Chest HRCT findings improved in 4 of 7 (57.1%) and 1 of 5 (20%) patients in the culture conversion and non-conversion groups, respectively., Conclusion: ALIS facilitated sputum culture conversion within 6 months in 58.3% of patients with refractory MAC-PD. Sputum culture conversion was significantly more frequent for CLA-susceptible strains and patients with fewer cavitary lesions. Improved CT findings after ALIS did not always correspond to sputum culture conversion., (© 2024. The Author(s).)

Introduction: Osimertinib is used as the first-line treatment for EGFR mutation-positive NSCLC. Nevertheless, its efficacy and safety in clinical practice remain to be fully elucidated and the pattern of progression and the optimal subsequent treatment after osimertinib remains unclear., Methods: This was a multicenter prospective observational study. EGFR mutation-positive patients with NSCLC who started first-line osimertinib from September 2018 to August 2020 were enrolled and followed up until August 2022., Results: A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: 17.6-21.7) months and 41.0 (95% CI: 37.1-44.1) months, respectively. Grade 3 or worse adverse events were observed in 136 patients (23.3%). Progression patterns were categorized as central nervous system only, oligo-progression, and multiple organs on the basis of the Response Evaluation Criteria in Solid Tumors-progressive disease and occurred in 37 (10.8%), 156 (45.4%), and 151 patients (43.9%). The patient's condition on progression was asymptomatic in 195 patients (56.7%). Osimertinib was continued in 163 patients (47.4%) after confirming progression. In clinically stable population with progressive disease (n = 247), survival after progression was 13.3 (95% CI: 10.9-16.4) months for those who continued osimertinib beyond progressive disease (n = 124), and 24.1 (95% CI: 17.7-34.0) months for those who discontinued osimertinib (n = 123) (hazard ratio = 2.01, 95% CI: 1.38-2.91, p  = 0.0002). Platinum plus pemetrexed had the best overall survival benefits after osimertinib., Conclusions: First-line osimertinib was found to have good effectiveness comparable to that reported in pivotal studies. Nevertheless, osimertinib should be discontinued among those who develop progression., Trial Registration Number: UMIN000038683., Competing Interests: Dr. Watanabe reports personal fees from AstraZeneca, Chugai Pharmaceutical, Merck Biopharma Co., Ltd., Amgen K.K., Novartis Pharma, Bristol-Myers Squibb, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Ono Pharmaceutical Co., Ltd., Riken Genesis Co., Ltd., Sysmex Corporation, and Takeda Pharmaceutical Company, Limited outside of the submitted work. Dr. Hosomi reports personal fees from AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda, Eisai, Novartis, and Pfizer outside the submitted work. Dr. Naoki reports personal fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim outside of the submitted work. Dr. Nakahara reports personal fees from Ono, Takeda, Eli Lilly, Kyowa Kirin, Boehringer Ingelheim, AstraZeneca, and Bristol-Myers Squibb outside of the submitted work. Dr. Tsukita reports personal fees from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Eli Lilly, Bristol-Myers Squibb, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, and Eisai outside of the submitted work. Dr. Matsumoto reports personal fees from AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Merck Sharp & Dohme, Nippon Kayaku Co., Ltd., and Kyowa Kirin Co., Ltd. outside of the submitted work. Dr. Yoh reports personal fees from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Janssen, Kyowa Kirin, Lilly, Merck Serono, Novartis, Ono, Otsuka, Taiho and Takeda and grants from 10.13039/100006483Abbvie, 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, Boehringer Ingelheim, 10.13039/100010795Chugai, 10.13039/501100022274Daiichi Sankyo, 10.13039/100014422Lilly, 10.13039/100009947Merck Sharp & Dohme, 10.13039/100004319Pfizer, Taiho, and Takeda outside of the submitted work. Dr. Fujisaka reports personal fees from AstraZeneca, Lilly, Boehringer Ingelheim, Takeda, Chugai Pharma, Ono Pharmaceutical, Pfizer, and Novartis, and grants from 10.13039/100004334Merck, 10.13039/100002491Bristol-Myers Squibb, 10.13039/100009857Regeneron, 10.13039/100009954Taiho Pharmaceutical, 10.13039/501100013170Ono Pharmaceutical outside of the submitted work. Dr. Takahashi reports personal fees from AstraZeneca, Bristol-Myers Squibb Japan, Chugai Pharma, Kyowa Kirin, Lilly Japan, Merck Sharp & Dohme, Nippon Kayaku, Taiho Pharmaceutical, and Takeda outside of the submitted work. Dr. Kishi reports personal fees from AstraZeneca outside of the submitted work. Dr. Naka reports personal fees from AstraZeneca, Chugai, Ono, and Merck Sharp & Dohme outside of the submitted work. Dr. Kunitoh reports personal fees from Taiho Pharmaceutical, Daiichi Sankyo, Merck Sharp & Dohme, Johnson and Johnson, and AstraZeneca outside of the submitted work. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Curcumin is a plant-derived secondary metabolite exhibiting antitumor, neuroprotective, antidiabetic activities, and so on. We previously isolated Escherichia coli as an enterobacterium exhibiting curcumin-converting activity from human feces, and discovered an enzyme showing this activity (CurA) and named it NADPH-dependent curcumin/dihydrocurcumin reductase. From soil, here, we isolated a curcumin-degrading microorganism (No. 34) using the screening medium containing curcumin as the sole carbon source and identified as Rhodococcus sp. A curcumin-degrading enzyme designated as CurH was purified from this strain and characterized, and compared with CurA. CurH catalyzed hydrolytic cleavage of a carbon-carbon bond in the β-diketone moiety of curcumin and its analogs, yielding two products bearing a methyl ketone terminus and a carboxylic acid terminus, respectively. These findings demonstrated that a curcumin degradation reaction catalyzed by CurH in the soil environment was completely different from the one catalyzed by CurA in the human microbiome. Of all the curcumin analogs tested, suitable substrates for the enzyme were curcuminoids (i.e., curcumin and bisdemethoxycurcumin) and tetrahydrocurcuminoids. Thus, we named this enzyme curcuminoid hydrolase. The deduced amino acid sequence of curH exhibited similarity to those of members of acetyl-CoA C-acetyltransferase family. Considering results of oxygen isotope analyses and a series of site-directed mutagenesis experiments on our enzyme, we propose a possible catalytic mechanism of CurH, which is unique and distinct from those of enzymes degrading β-diketone moieties such as β-diketone hydrolases known so far., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We herein report a case of Mycobacterium interjectum pulmonary disease (M. interjectum-PD) that improved considerably after azithromycin (AZM), rifampicin (RFP), and ethambutol (EB) therapy. A 69-year-old woman, managed locally for suspected NTM-PD based on chest computed tomography (CT) findings was referred to our hospital for worsening productive cough six years after the initial diagnosis. High-resolution chest CT showed right middle and left lower lobe bronchiectasis with middle and centrilobular nodules. Bronchial washing and sputum culture yielded M. interjectum. Treatment with AZM, RFP, and EB resulted in sputum culture conversion, and the chest CT findings subsequently improved. This is the first reported case of M. interjectum-PD in Japan.

Although outcomes have improved with new-generation drug-eluting stents, few reports have analyzed the risk factors associated with chronic outcomes of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). This study aimed to investigate the independent risk factors for target lesion revascularization (TLR) and major adverse cardiac and cerebrovascular events (MACCEs) after CTO-PCI using Japanese multicenter data. A total of 3,666 patients, who underwent CTO-PCI and completed a 1-year follow-up, registered at the Japanese CTO-PCI Expert Registry from 2014 to 2019, were examined. The primary outcome was defined as TLR, and the secondary outcome was MACCEs at the 1-year follow-up. TLRs and MACCEs occurred in 175 (4.8%) and 524 (14.3%) patients, respectively. Multivariate logistic regression analysis demonstrated that in-stent occlusion (ISO) (odds ratio [OR] 2.604, 95% confidence interval [CI] 1.695 to 4.001), hemodialysis (OR 1.784, 95% CI 1.062 to 2.997), diabetes mellitus with insulin use (OR 1.741, 95% CI 1.060 to 2.861), moderate-to-severe calcification (OR 1.726, 95% CI 1.197 to 2.487), and the right coronary artery as the target vessel (OR 1.468, 95% CI 1.018 to 2.117) were significantly associated with TLR. Hemodialysis (OR 2.214, 95% CI 1.574 to 3.113), ISO (OR 1.499, 95% CI 1.127 to 1.993), arteriosclerosis obliterans (OR 1.414, 95% CI 1.074 to 1.863), and multivessel disease (OR 1.356, 95% CI 1.117 to 1.647) were significantly associated with MACCEs. One-year outcomes of new-generation drug-eluting stents for CTO-PCI were favorable, and ISO as a lesion factor and hemodialysis as a patient factor were strongly associated with TLR and MACCEs, respectively., Competing Interests: Declaration of competing interest Dr. Tsuchikane is a consultant for Asahi Intecc, Boston Scientific, and Kaneka. Dr. Osamu Katoh is a consultant for Asahi Intecc, Nipro, and Canon Medical. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

The skin's protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Mycobacterium avium is associated with pulmonary disease in otherwise healthy adults. Several clarithromycin-refractory cases have been reported, including some cases caused by clarithromycin-susceptible strains., Objectives: To characterize the reason for the discrepancy between clinical response and antibiotic susceptibility results., Methods: We conducted population analysis of clarithromycin-tolerant and heteroresistant subpopulations of M. avium cultured in vitro and in homogenates of infected lungs of mice. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for 28 M. avium and two M. kansasii strains. Mice were intranasally infected with M. avium and treated with or without clarithromycin (100 mg/kg) thrice weekly. They were sacrificed on day 35 and the bacteria in lung homogenates were tested for clarithromycin resistance. Population analysis assays were performed based on colony growth on plates containing two-fold dilutions of clarithromycin., Results: The MBC/MIC ratios were ≥8 in all 28 strains of M. avium tested. In the population analysis assay, several colonies were observed on the plates containing clarithromycin concentrations above the MIC (2-64 mg/L). No growth of M. kansasii colonies was observed on the plates containing clarithromycin concentrations ≥2 mg/L. M. avium in the homogenates of infected lungs showed clearer clarithromycin-resistant subpopulations than in vitro, regardless of clarithromycin exposure., Conclusion: M. avium shows intrinsic heterogeneous resistance (heteroresistance) to clarithromycin. This may explain the observed discrepancies between clarithromycin susceptibility testing results and clinical response to clarithromycin treatment. Further studies are needed to confirm a link between heteroresistance and clinical outcomes., Competing Interests: Declaration of competing interest None., (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.)

Background: Endoscopic retrograde cholangiography (ERC)-related procedures, usually performed before biliary tract cancer (BTC) surgery, are associated with increased risk for various complications, which can cause sarcopenia. No study has previously elucidated the relationship between preoperative ERC-related procedures and sarcopenia/skeletal muscle mass loss., Methods: Patients with BTC who underwent radical surgical resection following ERC-related procedures were included. Skeletal muscle mass was evaluated using the psoas muscle mass index (PMI), which was determined using computed tomography images, and the change in PMI before the initial pre-ERC and surgery (ΔPMI) was calculated. Risk factors for advanced skeletal muscle mass loss, defined as a large ΔPMI, were evaluated., Results: The study cohort included 90 patients with a median age of 72 (interquartile range, 65-75) years. The median PMI pre-ERC and surgery was 4.40 and 4.15 cm 2 /m 2 , respectively (p < .01). The median ΔPMI was -6.2% (interquartile range, -10.9% to 0.5%). By multivariate analysis, post-ERC pancreatitis and cholangitis before surgery were independent predictive factors for large PMI loss (odds ratio, 4.57 and 3.18, respectively; p = .03 and p = .02, respectively)., Conclusions: Skeletal muscle mass decreases preoperatively in most patients with BTC undergoing ERC. Post-ERC pancreatitis and cholangitis before surgery were independent risk factors for large skeletal muscle mass loss., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

This study investigated the three-dimensional (3D) cellular interactions and tunneling nanotubes (TNTs) during fetal mouse skin regeneration on embryonic days 13 (E13) and 15 (E15). We aimed to understand spatial relationships among cell types involved in skin regeneration and assess the potential role of TNTs. Full-thickness skin incisions were performed in E13 and E15 embryos. Wound sites were collected, embedded in epoxy resin, processed for 3D reconstruction (1 μm thickness sections), and subjected to whole-mount immunostaining. We conducted in vitro co-culture experiments with fetal macrophages and fibroblasts to observe TNT formation. To assess the effect of TNTs on skin regeneration, an inhibiting agent (cytochalasin B) was administered to amniotic fluid. Results revealed that E13 epidermal keratinocytes interacted with dermal fibroblasts and macrophages, facilitating skin regrowth. TNT structures were observed at the E13-cell wound sites, among macrophages, and between macrophages and fibroblasts, confirmed through in vitro co-culture experiments. In vitro and utero cytochalasin B administration hindered those formation and inefficient skin texture regeneration at E13 wound sites. This emphasizes the necessity of 3D cellular interactions between epidermal and dermal cells during skin regeneration in mouse embryos at E13. The prevalence of TNT structures indicated their involvement in achieving complete skin texture restoration., (© 2024. The Author(s).)

Wounds that occur in adults form scars due to fibrosis, whereas those in embryos regenerate. If wound healing in embryos is mimicked in adults, scarring can be reduced. We found that mouse fetuses could regenerate tissues up to embryonic day (E) 13, but visible scars remained thereafter. This regeneration pattern requires actin cable formation at the epithelial wound margin via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). Here, we investigated whether the AMPK-activating effect of salicylate, an anti-inflammatory drug, promotes regenerative wound healing. Salicylate administration resulted in actin cable formation and complete wound regeneration in E14 fetuses, in which scarring should have normally occurred, and promoted contraction of the panniculus carnosus muscle, resulting in complete wound regeneration. In vitro, salicylate further induced actin remodeling in mouse epidermal keratinocytes in a manner dependent on cell and substrate target-specific AMPK activation and subsequent regulation of Rac1 signaling. Furthermore, salicylate promoted epithelialization, enhanced panniculus carnosus muscle contraction, and inhibited scar formation in adult mice. Administration of salicylates to wounds immediately after injury may be a novel method for preventing scarring by promoting a wound healing pattern similar to that of embryonic wounds., (© 2024. The Author(s).)

Background: Subungual exostosis is a type of heterotopic ossification, which often has unclear margins. Therefore, marginal resection may cause recurrence and wide resection is sometimes required to achieve a complete cure. However, wide resection may cause postoperative nail deformity and revision of this deformity is generally difficult. The primary treatment of subungual exostosis is surgical treatment, and there have been no comprehensive reports on the efficacy of adjunctive treatments. Although postoperative electron beam irradiation has been successfully used after heterotopic ossification excision to prevent recurrence, there are no reports on the use of this procedure following subungual exostosis resection., Case Description: Herein, we report a case of refractory subungual exostosis that developed as a result of chronic irritation and inflammation caused by an ingrown nail and recurred after initial resection. We performed marginal resection of the lesion to preserve the nail matrix and nail bed as possible, a two-stage skin grafting procedure, and electron-beam irradiation to prevent recurrence., Conclusions: Excellent results were achieved both in terms of complete cure and cosmetic appearance, suggesting that electron-beam irradiation following refractory subungual exostosis excision may help prevent its recurrence. We expect a further study including many cases of subungual exostosis treated with postoperative electron-beam irradiation to be conducted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-26/coif). N.I. serves as an unpaid editorial board member of AME Case Reports from December 2023 to November 2025. The other authors have no conflicts of interest to declare., (2024 AME Case Reports. All rights reserved.)

Background: Despite the effectiveness of the retrograde approach for chronic total occlusion (CTO) lesions, there are no standardized tools to predict the success of retrograde percutaneous coronary intervention (PCI)., Objectives: The aim of this study was to develop a prediction tool to identify CTO lesions that will achieve successful retrograde PCI., Methods: This study evaluated data from 2,374 patients who underwent primary retrograde CTO-PCI and were enrolled in the Japanese CTO-PCI Expert Registry between January 2016 and December 2022 (NCT01889459). All observations were randomly assigned to the derivation and validation cohorts at a 2:1 ratio. The prediction score for guidewire failure in retrograde CTO-PCI was determined by assigning 1 point for each factor and summing all accrued points., Results: The JR-CTO score (moderate-severe calcification, tortuosity, Werner collateral connection grade ≤1, and nonseptal collateral channel) demonstrated a C-statistic for guidewire failure of 0.72 (95% CI: 0.67-0.76) and 0.71 (95% CI: 0.64-0.77) in the derivation and validation cohorts, respectively. Patients with lower scores had higher guidewire and technical success rates and decreased guidewire crossing time and procedural time (P < 0.01)., Conclusions: The JR-CTO (Japanese Retrograde Chronic Total Occlusion) score, a simple 4-item score that predicts successful guidewire crossing in patients undergoing retrograde CTO-PCI, has the potential to support clinical decision-making for the retrograde approach., Competing Interests: Funding Support and Author Disclosures This study is funded by the Japanese Board of Chronic Total Occlusion Interventional Specialists which is funded by Asahi Intecc, Abbott Vascular Japan, Biosensors Japan, Boston Scientific, Daiichi-Sankyo, Kaneka Medix, Medtronic Japan, NIPRO, and Terumo. Dr Tsuchikane is a consultant for Asahi Intecc, Boston Scientific Japan, and Kaneka Corporation. Dr Oikawa has received speaker honoraria from Abbott Medical Japan, Boston Scientific Japan, Medtronic Japan, Nipro, TERUMO, Kaneka, and OrbusNeich Medical Corporation. Dr Ito has received speaker honorariums from Boston Scientific Japan, Abbott Medical Japan, TERUMO, and Medtronic Japan Corporation. Dr Yoshikawa has received speaker honoraria from TERUMO, Abbott Medical Japan, Kaneka, Nipro, and OrbusNeich Medical Corporation. Dr Kawasaki has received speaker honoraria from Abbott Medical Japan, Boston Scientific Japan, Japan Lifeline, Medtronic Japan, and Amgen Corporation. Dr Okamura has received a speaker honorarium from TERUMO Corporation. Dr Sumitsuji has received speaker honoraria from TERUMO Medtronic Japan, Nipro, Abbott Medical Japan, Asahi Intecc, Boston Scientific Japan, Cook Japan, Astellas Pharma, Bayer Pharma, Amgen, Boehringer Ingelheim Japan, Heart organization, Kowa, Abiomed Japan, SHIMADZU, Kaneka, HeartFlow Japan, Cuorips, Daiichi-Sankyo, and Fuji Film Medical Corporation, is as a consultant for Asahi Intecc, Cuorips, and Heart Organization Corporation. Dr Katoh is a consultant for Asahi Intecc, Nipro, and Canon Medical System Corporation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate ( p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC.

Competing Interests: Conflict of interest: None declared.

Unlike adult mammalian wounds, early embryonic mouse skin wounds completely regenerate and heal without scars. Analysis of the underlying molecular mechanism will provide insights into scarless wound healing. Twist2 is an important regulator of hair follicle formation and biological patterning; however, it is unclear whether it plays a role in skin or skin appendage regeneration. Here, we aimed to elucidate Twist2 expression and its role in fetal wound healing. ICR mouse fetuses were surgically wounded on embryonic day 13 (E13), E15, and E17, and Twist2 expression in tissue samples from these fetuses was evaluated via in situ hybridization, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction. Twist2 expression was upregulated in the dermis of E13 wound margins but downregulated in E15 and E17 wounds. Twist2 knockdown on E13 left visible marks at the wound site, inhibited regeneration, and resulted in defective follicle formation. Twist2-knockdown dermal fibroblasts lacked the ability to undifferentiate. Furthermore, Twist2 hetero knockout mice (Twist + /-) formed visible scars, even on E13, when all skin structures should regenerate. Thus, Twist2 expression correlated with skin texture formation and hair follicle defects in late mouse embryos. These findings may help develop a therapeutic strategy to reduce scarring and promote hair follicle regeneration., (© 2024. The Author(s).)

Background : There are only a few reports on the nutritional status and mortality of patients with idiopathic pulmonary fibrosis (IPF). As such, this study aims to investigate the relationship between controlling nutritional status (CONUT) and the mortality of elderly patients with IPF. Methods : A total of 170 IPF patients aged ≥65 years old who visited the rehabilitation department of our hospital between July 2014 and July 2021 (mean age: 75.7 ± 6.3 years, sex (male/female): 138/32, %FVC: 78.3 ± 18.3%) were retrospectively analyzed. The Kaplan-Meier method and log-rank test were applied. Furthermore, using a Cox proportional hazards model with multivariate analysis, we analyzed the relationship between all-cause mortality and baseline characteristics including CONUT. Results : Based on the CONUT score, the normal group included 101 cases, the mild group included 58 cases, the moderate group included 11 cases, and the severe group had 0 cases. There were 49 cases of all-cause mortality events, suggesting that the mortality of the moderate group was significantly poorer than that of the normal and mild groups ( p < 0.05). Furthermore, multivariate analysis identified GAP stage (HR: 5.972, 95%CI: 2.901~12.291, p < 0.0001), mMRC scale (HR: 0.615, 95%CI: 0.389~0.971, p = 0.009), and CONUT (HR: 2.012, 95%CI: 1.192~3.395, p = 0.037) as factors significantly influencing mortality. Conclusions : Severe malnutrition was not observed in elderly patients with IPF. Moderate malnutrition was associated with a significantly higher risk of all-cause mortality, suggesting that CONUT is an important indicator for predicting mortality.

Eyelid malignancies are often resected in the entire layer, typically requiring anterior and posterior lamellae reconstruction. Posterior lamella reconstruction has been reported using grafts from the nasal septum, palatal mucosa, and auricular cartilage, which have advantages and disadvantages. The authors performed anterior and posterior lamellar reconstruction using a local skin flap and stripe-shaped anti-helical cartilage with the perichondrium in 3 total defect cases after basal cell carcinoma resection of the lower eyelid. The auricular cartilage was excised in strips with the surrounding perichondrium attached and simultaneously reconstructed, with the auricular cartilage as the tarsal and the perichondrium as the conjunctival substitute. In all 3 cases, good results were obtained without eyelid ectropion or corneal irritation 1 year postoperatively. No auricular deformities were observed. However, partial lower eyelid ptosis was observed in 2 cases. In future cases, correctively over-fixating the lower eyelid morphology is necessary., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227., (© 2024. The Author(s).)

Background: Various flap monitoring techniques have been used in the early detection of anastomotic thrombus; however, the use of automatic and continuous monitoring methods is presently uncommon. The purpose of this study was to investigate trends in interstitial fluid glucose concentration (IFG) in flap monitoring by measuring IFG automatically and continuously. Methods: Nine patients underwent unilateral breast reconstruction using a transverse rectus abdominis myocutaneous flap with vascular anastomosis. Two IFG measuring devices were attached to each patient. One device was attached to the flap (flap IFG) and the other to the healthy breast (control IFG). In each case, flap IFG, control IFG, and IFG ratio (flap IFG/control IFG) were recorded in the initial 72 h post-surgery (first half) and also in the subsequent 72 h (second half). In all of the cases, the mean values recorded in the first half and those in the second half were compared. Results: All flaps survived. The flap IFG didn't fall below 40 mg/dL in the first half. The minimum flap IFG and IFG ratio were 42 mg/dL and 0.55 in the first half. The flap IFG was significantly higher in the first half than in the second half in all cases, and the IFG ratio was similar in 8 cases. Furthermore, mean flap IFG and mean IFG ratio in all cases in the first half were significantly higher than in the second half. Conclusions: IFG measurements may complement conventional flap monitoring, particularly in the early postoperative period., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: (I) Conception and design: Naohiro Ishii; (II) Administrative support: Kyoichi Matsuzaki, Kazuo Kishi; (III) Provision of study materials or patients: Naohiro Ishii; (IV) Collection and assembly of data: Naohiro Ishii, Tomoki Kiuchi; (V) Data analysis and interpretation: Takahiro Uno, Yuichiro Uoya,Shigeki Sakai, Tomoki Kiuchi; (VI) Manuscript writing: All authors; and (VII) Final approval of manuscript: All authors., (© 2022 The Author(s).)

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress., Competing Interests: Declaration of competing interest Masashi Bando received lecture fees from AstraZeneca K.K., Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Sakae Homma received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. and belongs to Endowed departments by Shionogi & Co., Ltd., Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Hiroshi Date received lecture fees from Covidien Japan Inc. and Johnson & Johnson K.K. and donations from Adachi Co., Ltd., Hogy Medical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. Kazuma Kishi received lecture fees from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from MSD K. K., Taiho Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. and donations from Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Nippon Boehringer Ingelheim Co., Ltd. Atsushi Miyamoto received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Takeo Nakayama received lecture fees from Eli Lilly Japan K.K., Pfizer Japan, Inc. and Janssen Pharmaceutical K.K. and research finding from I&H Co., Ltd., Cocokarafine Group Co., Ltd. And Konica Minolta, Inc. and donations from Cancerscan Inc. and Yuyama Manufacturing Co., Ltd. Arata Azuma received lecture fees from Taiho Pharmaceutical Co., Ltd., Toray Industries, Inc. and Nippon Boehringer Ingelheim Co., Ltd. Yasuhiro Kondoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K. and Janssen Pharmaceutical K.K. Takeshi Johkoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Yasuhiko Nishioka received lecture fees from MSD K. K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from Taiho Pharmaceutical Co., Ltd., TMS Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Bonac Corporation and donations from Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Eli Lilly Japan K.K. Junya Fukuoka received research funding from National Institute of Advanced Industrial Science and Technology and Future Corporation. Yasunari Miyazaki received donations from Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and lecture fees from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd. Ichiro Yoshino received lecture fees from MSD K. K., AstraZeneca K.K., Intuitive Surgical G.K., Ono Pharmaceutical Co., Ltd., Covidien Japan Inc., Johnson & Johnson K.K., Daiichi Sankyo Company, Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. and Eli Lilly Japan K.K. and donations from Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Pfizer Japan, Inc. Takafumi Suda received lecture fees from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from Chugai Pharmaceutical Co., Nippon Boehringer Ingelheim Co. and Bristol-Myers Squibb K.K. and donations from Shionogi & Co., Ltd. and Chugai Pharmaceutical Co. Yoshihito Goto, Susumu Sakamoto and Hiroyoshi Yamauchi have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Although the coronary chronic total occlusion (CTO) crossing algorithm has been published, the characteristics associated with the first strategy selection for short-length lesions <20 mm is still debatable. This study aimed to determine the characteristics associated with primary retrograde approach (PRA) for native CTO with short occlusion length in percutaneous coronary intervention (PCI). Between January 2014 and December 2021, we examined data on 4,088 lesions in the Japanese CTO-PCI Expert Registry with occlusion lengths <20 mm. Then, the characteristics for short-length CTO, which was performed by way of the PRA, were assessed. PRA was performed in 785 patients (19.2%). The guidewire success rate was 93.6%, and the technical success rate was 91.3%. Previous coronary artery bypass grafting, chronic kidney disease, and 6 lesion/anatomic characteristics (i.e., blunt stump, distal runoff <1 mm, CTO lesion tortuosity, reattempt procedures, ostial location, and the presence of collateral channel grade 2) were associated with PRA (p <0.05). Moreover, hemodialysis was an independent factor of unsuccessful anterograde guidewire crossing, along with distal runoff <1 mm, the existence of calcification, and CTO lesion tortuosity (all p <0.05). In clinical settings, these independent factors for PRA in short-length CTO can help in selecting the CTO-PCI strategy., Competing Interests: Declaration of competing interest Dr. Tsuchikane reports financial support was provided by Boston Scientific Japan, Asahi Intecc, and Kaneka. Dr. Oikawa reports financial support was provided by Boston Scientific Japan, Abott Medical, Terumo, Medtronic, NIPRO, Kaneka, and OrbusNeich Medical. Dr. Yoshikawa reports financial support was provided by Terumo Interventional Systems, Kaneka, Abbott Medical, NIPRO, and OrbusNeich Medical. Dr. Okamura reports financial support was provided by Terumo Interventional Systems. Dr. Katoh reports financial support was provided by Asahi Intecc Co Ltd, NIPRO, and Canon Medical. Dr. Ito reports financial support was provided by Boston Scientific Japan, Abbott Medical, Terumo, and Medtronic. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis., Patients and Methods: We retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system., Results: The median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and anti -glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis., Conclusion: The diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Makoto Hayashi reports a relationship with Showa University Northern Yokohama Hospital that includes: speaking and lecture fees. 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., (© 2024 The Authors.)

Objective: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited., Methods: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information., Results: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively., Conclusions: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings., (© The Author(s) 2024. Published by Oxford University Press.)

Objective The presence of a short white hair-like appearance in the lower esophagus has recently been noted during esophagogastroduodenoscopy (EGD) at our institution. Histological findings showed that this formation was a spiked protrusion of the esophageal papilla. The results regarding the prevalence of such lesions in individuals who underwent EGD examinations as part of medical checkup procedures are herein presented. Methods The EGD results of 14,338 individuals (9,225 males, 5,113 females; mean age 54.0±9.8 years) were examined. The findings related to the presence of multiple lesions with a short white hair-like appearance in the lower esophagus of patients with reflux esophagitis, esophageal squamous papilloma, or gastric mucosal atrophy (GMA), as well as the hiatal hernia width, were investigated. Results Endoscopic findings indicating short white hair-like appendages in the lower esophagus were noted in 167 patients, with a prevalence rate of 1.2%. A female sex, younger age, lower body mass index, lower percentages of habitual smoking and drinking, and the presence of esophageal squamous papilloma were characteristic features of cases with such findings. In addition, a significantly lower prevalence of reflux esophagitis and a smaller diaphragmatic hiatus size were observed. A multiple logistic regression analysis indicated that a female sex, absence of reflux esophagitis, presence of esophageal squamous papilloma, and a smaller diaphragmatic hiatus were factors significantly related to the presence of these short white hair-like appendages. An analysis of circumferential localization revealed the main location to be the left-posterior wall. Conclusion This study is the first to report the prevalence of multiple short white hair-like appendages in the lower esophagus. The occurrence of such lesions is inversely associated with the presence of reflux esophagitis.

This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned. A blood test on the 1st day after the operation showed elevated levels of AST 537 U/L, ALT 616 U/L, and 7 hours later blood sampling showed further increases in AST 1,455 U/L, ALT 1,314 U/L. After a detailed review of the preoperative CT, celiac artery stenosis due to compression of the arcuate ligament was suspected, and urgent median arcuate ligament release was performed on the same day. Dissection of the arcuate ligament significantly improved the pulsation of the common hepatic artery and proper hepatic artery. Postoperatively, hepatic enzymes improved and ISGPS showed Grade B pancreatic juice leakage, but the patient was discharged from the hospital on the 49th postoperative day without any other complications. He took S-1 as adjuvant chemotherapy, and no signs of recurrence have been observed 9 months after the operation.

Background: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer., Methods: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively., Results: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P  < 0.03) and 12 months (P  < 0.001) were independent prognostic factors for a shorter recurrence-free interval., Conclusions: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer., Clinical Trial Registration: UMIN000007925., (© 2024. The Author(s).)

Deeply etched forehead creases indicate aging. Various treatments such as filler injections, fat grafting, and facelift surgery are used to remove them. However, knowledge of the anatomical structures associated with subcutaneous tissue changes and the superficial musculoaponeurotic system is lacking, and there is no consensus about the appropriate treatment. We have investigated the subcutaneous structures involved in forehead creases; this will help to establish selection criteria for improved treatment. The forehead sections of five unfixed adult Asian cadavers were obtained. Tissues containing forehead creases were removed from the periosteum and were examined using gross observation, radiography, histology, and nano-computed tomography. All methods revealed that the dermis in the skin crease area, namely the fold visible from the body surface, was bound to the frontalis muscle by a three-dimensional fibrous structure between the fatty septa. This structure was dense near the skin folds and sparse and thin in other areas. In particular, it was tightly bound to the dermis immediately below the crease, with collagen fibers traversing toward the epidermis. In addition, there were fewer skin appendages near the crease than in the normal area, or they were absent altogether; the epidermis was thicker, and the dermal papillae were more developed. It is thought that the density and firmness of the fibrous fatty septal structures between the dermis-frontalis muscle and the specific structures of the epidermis and dermis immediately below the crease account for the characteristic plastic forehead creases., (© 2023 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

This case series aimed to describe a new technique for correcting contractures and deformities that reliably addresses lacrimal punctum deviation and severe cicatricial lower eyelid ectropion. This was a technical description and a retrospective interventional case series. Eyelid ectropion and lacrimal punctum deviation were treated surgically by grafting the fascia lata and suturing the tarsus-Horner muscle. In total, three patients underwent this surgery: one for burns, one for lower eyelid tumor resection, and the other for an orbital floor fracture following a motorcycle accident, all resulting in ectropion. All patients previously had failed ectropion correction procedures, including scar revision, skin grafting, auricular cartilage grafting, and lateral tarsal strips. The mean follow-up was 15.8 (12.5-18.5) months. Furthermore, all patients showed resolution of lower eyelid ectropion and significant improvement in lower eyelid contracture, with a mean increase of 4.0 (2.5-5) mm. No severe complications were observed, and they reported a significant improvement in ocular surface symptoms. Our study shows that tacking of the tarsus and Horner muscles in combination with fascia lata grafting is effective in correcting refractory cicatricial lower eyelid ectropion with deviation of the tear punctum., Competing Interests: The authors have no financial or other conflicts of interest to disclose. No funding was received for conducting this study., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)