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Importance: The management of papillary thyroid carcinoma (PTC), particularly in cases with clinically apparent lateral neck lymph node metastasis (cN1b), remains an area of debate. The surgical options for PTC, including total thyroidectomy and lobectomy, have distinct impacts on patients' outcomes and quality of life., Objective: To compare survival and recurrence outcomes between patients who underwent a lobectomy plus ipsilateral lateral neck dissection (LND) and those who underwent a total thyroidectomy plus ipsilateral LND for intermediate-risk cN1b PTC with both primary tumors and lymph node metastases in the ipsilateral neck region., Design, Setting, and Participants: This retrospective cohort study was conducted at Ito Hospital, Tokyo, Japan. Patients who underwent surgery for PTC between January 2005 and December 2012 were included, and those with high-risk PTCs and concurrent other thyroid cancers were excluded. Data were analyzed from April to August 2024., Exposures: Lobectomy plus LND vs total thyroidectomy plus LND., Main Outcomes and Measures: An inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier analysis and a Cox proportional hazards regression analysis were performed to compare the patients' overall survival, recurrence-free survival (RFS), and modified RFS (which considered the potential need for a future contralateral lobectomy)., Results: Of 401 included patients, 317 (79.1%) were female, and the median (IQR) age was 47 (36-59) years. A total of 157 patients underwent lobectomy plus ipsilateral LND and 244 underwent total thyroidectomy plus ipsilateral LND. The median (IQR) follow-up time was 13.0 (11.2-15.0) years. The IPTW-adjusted overall survival rates at 5, 10, and 15 years were 98.0% (95% CI, 93.9-99.3), 97.5% (95% CI, 93.2-99.1), and 96.8% (95% CI, 92.2-98.7), respectively, for the lobectomy group vs 99.4% (95% CI, 97.0-99.9), 97.4% (95% CI, 94.4-98.8), and 96.9% (95% CI, 93.3-98.5), respectively, for the total thyroidectomy group (hazard ratio [HR], 1.10; 95% CI, 0.35-3.47). The IPTW-adjusted RFS rates at 5, 10, and 15 years were 93.8% (95% CI, 88.5-96.7), 88.4% (95% CI, 82.0-92.6), and 84.1% (95% CI, 76.8-89.3), respectively, for the lobectomy group vs 95.4% (95% CI, 91.8-97.4), 92.9% (95% CI, 88.8-95.5), and 87.8% (95% CI, 80.8-92.4), respectively, for the total thyroidectomy group (HR, 1.41; 95% CI, 0.79-2.54). The IPTW-adjusted modified RFS rates at 5, 10, and 15 years were 96.7% (95% CI, 92.2-98.6), 93.8% (95% CI, 88.5-96.7), and 88.9% (95% CI, 82.4-93.1), respectively, for the lobectomy group vs 95.4% (95% CI, 91.8-97.4), 92.9% (95% CI, 88.8-95.5), and 87.8% (95% CI, 80.8-92.4), respectively, for the total thyroidectomy group (HR, 0.93; 95% CI, 0.49-1.76)., Conclusions and Relevance: In this study, for these selected intermediate-risk cN1b PTC cases, total thyroidectomy and lobectomy provided comparable outcomes in terms of prognosis and recurrence. These data may help inform future guideline revisions and support joint decision-making between patients and their clinicians.

Background/aim: Various biomarkers are utilized in the field of breast cancer. Human lymphocyte antigen (HLA) class I molecules have a critical role in cancer immune surveillance. Therefore, this study aimed to assess the HLA class I expression and analyze the correlation with clinicopathologic factors in breast cancer., Patients and Methods: We investigated the clinical pathology archives of 150 consecutive patients with breast cancer who underwent a curative operation at the Sapporo Medical University, Japan, from January 2012 to December 2014. Immunohistochemical staining was used to evaluate HLA class I expression and CD8-positive T cell infiltration. The Pearson χ 2 test was used to assess HLA class I expression level and clinicopathological parameters. The Kaplan-Meier method was used to evaluate survival and the log-rank test to analyze the differences between survival curves., Results: Patients with dull/negative HLA class I had significantly poor disease-free survival (DFS) compared with those with positive HLA class I (p=0.0073). Univariate analyses revealed that pT, pN, positive lymphatic invasion, and dull/negative HLA class I were significantly associated with DFS. Multivariate analyses revealed dull/negative HLA class I as an independent poor prognostic factor (hazard ratio=2.75, 95% confidence interval=1.30-5.80, p=0.008)., Conclusion: HLA class I expression level may have a very sensitive prognostic effect on patients with breast cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Papillary thyroid microcarcinoma (PTMC) management has evolved, with active surveillance (AS) gaining prominence as a management option. However, a key concern for both clinicians and patients is the potential for patient loss to follow-up during AS., Aims: This study aimed to determine adherence and loss-to-follow-up rates in low-risk PTMC patients undergoing AS versus surgical intervention, in order to gain insights into clinical pathways and safety profiles., Materials and Methods: This cohort study analyzed the 2016 data from a single registered institution of Japan's public National Cancer Registry., Results: We identified and retrospectively analyzed the cases of 327 patients diagnosed with low-risk PTMC; 227 patients chose to undergo AS while the other 100 underwent PTMC surgery. Main outcomes were the adherence rate and loss-to-follow-up rate of each group, factors influencing discontinuation, and safety considerations. The rate of AS adoption was substantial in the complete series of 327 low-risk PTMC patients (69.4%). There was a significantly higher loss-to-follow-up rate at 5 years in the AS group (28.6%) compared to the Surgery group (17.8%) (HR 1.62, 95% CI: 1.01-2.61; p = 0.046). Both univariate and multivariate analyses confirmed the significantly higher loss-to-follow-up rate in the AS group as well as in older patients. No deaths due to PTMC progression were observed in the cases lost to follow-up., Conclusion: Despite concerns about loss to follow-up, active surveillance remains a safe option for low-risk PTMCs. Consistent follow-up strategies are crucial, and further research is needed to enhance patient counseling and care for the management of patients with PTMC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Limited data exist regarding drug-coated balloon (DCB) treatment in de novo large coronary arteries. We sought to demonstrate procedural characteristics, residual stenosis, and clinical outcomes following DCB angioplasty for de novo lesions in large versus small coronary arteries. The study included 184 consecutive patients with 223 de novo coronary lesions undergoing paclitaxel DCB angioplasty between January 2019 and August 2020, who were divided according to whether the DCB diameter was ≥ 3.0 mm (large group, n = 58) or < 3.0 mm (small group, n = 125). The large group had a higher proportion of acute coronary syndrome more commonly with ostial, bifurcation, and calcified lesions in large vessels and received lesion preparation with more frequent use of scoring or cutting balloons and atherectomy devices compared to the small group. Postprocedural angiographic diameter stenosis was smaller in the large group compared to the small group (31% [22-37] vs. 35% [26-42], p = 0.032), and intravascular ultrasound revealed no significant difference in postprocedural area stenosis between the groups (66.2 ± 7.7% vs. 67.9 ± 7.8%; p = 0.26). The median follow-up duration was 995 days. The incidence of a composite of all-cause death, myocardial infarction, stroke, or target lesion revascularization was similar between the groups (log-rank p = 0.41) and was influenced by the presence of acute coronary syndrome and anemia but not by DCB diameter. The rate of cardiovascular outcomes after DCB treatment was comparable in de novo large and small coronary arteries. Notably, well-planned lesion preparation with intravascular imaging guidance was prevalent in large vessels., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke., Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset., Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022., Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset., Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test., Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups., Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study., Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no anti-inflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPARα and its ligands on inflammatory response and PGC-1α gene expression in LPS-treated C2C12 myotubes. Knockdown of PPARα, whose expression was upregulated upon differentiation, augmented IL-6 or TNFα gene expression. Conversely, PPARα overexpression or its activation by ligands suppressed 2-h LPS-induced cytokine expression, with pemafibrate attenuating NF-κB or STAT3 phosphorylation. Of note, reduction of PGC-1α gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPARα in inflammatory response of C2C12 myotubes and suggest a future possibility of PPARα ligands as a candidate for anti-inflammatory therapy against sarcopenia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomohiro Tanaka reports a relationship with Kowa Company Ltd that includes: speaking and lecture fees. All the other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is a paucity of data regarding the optimal duration of drug-coated balloon (DCB) inflation for coronary lesions. We sought to explore the effect of DCB angioplasty with versus without long inflation time on residual stenosis and clinical outcomes in patients with coronary artery disease., Methods: This study included 314 consecutive patients with 445 lesions undergoing paclitaxel DCB angioplasty using different inflation time, divided according to whether the total inflation time of the DCB was ≥180 s (prolonged group) or <180 s (standard group). The primary clinical endpoint, defined as a composite of all-cause death, myocardial infarction, stroke, or target lesion revascularization, was examined in 92 propensity score matched pairs., Results: In the matched cohort, the median clinical follow-up period was 947 days. Postprocedural angiographic diameter stenosis was smaller in the prolonged group than in the standard group (30.0% [22.0-37.0] vs. 33.5% [25.5-40.5]; p = 0.042). Intravascular ultrasound measurements revealed that longer DCB inflation time resulted in smaller area stenosis (66.6 ± 7.8% vs. 69.4 ± 7.0%; p = 0.044) and a less mean increase in percent atheroma volume (-11.2 ± 7.1% vs. -7.4 ± 5.9%; p = 0.004) after angioplasty. The rate of the primary endpoint was lower in the prolonged group than in the standard group (log-rank p = 0.025). The efficacy of prolonged DCB inflation was prominent in patients with in-stent restenosis and longer lesions., Conclusion: Prolonged DCB inflation was associated with reduced residual stenosis and improved clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention. Prospective randomized trials are warranted to validate the benefits of DCB angioplasty with long inflation time., (© 2023 Wiley Periodicals LLC.)

Orchid mycorrhiza (OM) represents an unusual symbiosis between plants and fungi because in all orchid species carbon is provided to the host plant by the mycorrhizal fungus at least during the early stages of orchid development, named a protocorm. In addition to carbon, orchid mycorrhizal fungi provide the host plant with essential nutrients such as phosphorus and nitrogen. In mycorrhizal protocorms, nutrients transfer occurs in plant cells colonized by the intracellular fungal coils, or pelotons. Whereas the transfer of these vital nutrients to the orchid protocorm in the OM symbiosis has been already investigated, there is currently no information on the transfer of sulfur (S). Here, we used ultra-high spatial resolution secondary ion mass spectrometry (SIMS) as well as targeted gene expression studies and laser microdissection to decipher S metabolism and transfer in the model system formed by the Mediterranean orchid Serapias vomeracea and the mycorrhizal fungus Tulasnella calospora. We revealed that the fungal partner is actively involved in S supply to the host plant, and expression of plant and fungal genes involved in S uptake and metabolism, both in the symbiotic and asymbiotic partners, suggest that S transfer most likely occurs as reduced organic forms. Thus, this study provides original information about the regulation of S metabolism in OM protocorms, adding a piece of the puzzle on the nutritional framework in OM symbiosis., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

The present study aimed to evaluate the rate of positive surgical margins for magnetic resonance imaging (MRI) performed in the supine position prior to breast-conserving surgery (BCS). The rate of positive surgical margins and the clinicopathological factors were examined in consecutive patients with BCS who underwent preoperative MRI performed in the supine position at Sapporo Medical University Hospital (Sapporo, Japan) and related hospitals and clinics between January 2012 and December 2013. Of 1,175 eligible patients, 1,150 were included after excluding 25 patients with either bilateral breast cancer or stage IV disease. Positive margin was defined as no cancer seen on the resected margin. The primary endpoint was the rate of positive surgical margins when preoperative MRI was performed in the supine position and the secondary endpoint was identification of the factors that predict positive margins. Of the 1,150 female patients (median age, 55 years; range, 29-97 years) who underwent BCS for breast cancer following MRI performed in the supine position, 215 (18.8%) had positive margins, which is similar to the rate with MRI in the prone position, and 930 (81.2%) had negative margins. The rate of positive surgical margins in patients of the human epidermal growth factor receptor 2 (HER2) type was significantly higher than that in the non-HER2 type group (6.5 and 2.9%; χ 2 P=0.0103). There was no increase in the rate of positive margins in breast cancers with a diameter of >T2. The rate of positive surgical margins following MRI performed in the supine position was 18.8%. Supine MRI appears to be suitable for informing on the extent of resection of breast cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

The proper use of anthracycline-containing regimens in combination with anti-HER2-targeted therapy in a neoadjuvant setting for patients with HER2-positive breast cancer has not been resolved. Regimens preceded by anthracyclines have become the standard of care, and although the order has no significant impact on HER2-negative breast cancer, it is inconclusive as to whether a taxane-first sequence would have a similar effect on HER2-positive breast cancer. The present study aimed to investigate the benefit of a taxane-first sequence and of adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab and docetaxel (PTD). The present single-center prospective observational study was performed to investigate PTD followed by AC, and aimed to clarify the cCR rate after PTD alone and the pathological clinical response (pCR) rate after subsequent AC in patients without cCR after PTD alone. A total 24 patients were analyzed; of these, 14 achieved pCR (pCR rate, 58.3%). While four of 14 patients (28.6%) in the intention-to-treat population achieved pCR, nine of 14 patients (64.3%) achieved pCR with AC but not cCR after PTD. The median tumor reduction rate after four cycles of PTD was 58.9% (range, 20.8-100%) in all 24 patients, whereas the reduction rate after PTD-AC was 76.9% (range, 31.1-100%). Cardiac serious adverse events occurred in three patients (12.5%). In conclusion, a high pCR rate was observed for the taxane-first sequence. Patients were highly responsive to PTD, but some cases achieved additional antitumor effects after AC, which resulted in pCR without cCR after PTD alone. Since cardiotoxicity remains a significant problem, a higher risk-benefit treatment strategy is required to aim for AC omission. Trial registration number: UMIN000046338, name of registry: UMIN-CTR, date of registration: December 10, 2021., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Shima et al.)

Marathon is rarely used in coil embolization for an aneurysm; particularly, there have been no reports about distal anterior cerebral artery aneurysms. We have reported a case of successful use of Marathon in coil embolization in case of a distal anterior cerebral artery aneurysm. The patient was an 83-year-old woman. She had undergone coil embolization for an unruptured distal anterior cerebral artery aneurysm, which was discovered by chance. Our initial approach involved the use of a combination of Traxcess and Excelsior SL-10, but the use of SL-10 could not follow Traxcess because the right anterior cerebral artery from the right internal carotid artery had a sharp bifurcation. However, by switching to a combination of TENROU and Marathon, we could access the aneurysm. We thereby decided to continue the use of Marathon in order to complete the coil embolization. In coil embolization for an aneurysm, Marathon was found to be useful, depending on the location of the aneurysm and access route., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Fukutome et al.)