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Objectives: This study aimed to evaluate the relationship between bacteriological findings and wound healing after minor amputation in the treatment of chronic limb-threatening ischemia (CLTI) with infection. Methods: This single-center retrospective study analyzed 135 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy (EVT) and minor forefoot amputation for CLTI with wound infection between November 2017 and August 2021. The Kaplan-Meier method was used to assess the rate of wound healing after the procedure. The Cox proportional-hazards model was used to examine the impact of bacteriological findings and baseline characteristics on wound healing. Results: The wound healing rate at 6 months was 72.6%. In a multivariate analysis, in addition to hemodialysis (hazard ratio [HR]=1.73; p=0.009) and amputation above the metatarsophalangeal (MP) joint (HR=1.81; p=0.006), antimicrobial-resistant bacterial infection (HR=1.80, p=0.004) and polymicrobial infection (H=1.51; p=0.049) were predictors of delayed wound healing. Conclusion: Antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the MP joint were independent predictors of delayed wound healing after EVT and minor forefoot amputation in patients with CLTI and bacterial wound infection. Clinical Impact: In this single-center retrospective study, we analyzed 136 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy and minor forefoot amputation for chronic limb-threatening ischemia (CLTI) with wound infection between November 2017 and August 2021. Our main findings were that antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the metatarsophalangeal joint were independent predictors of delayed wound healing after minor amputation. This is the first report of the association between bacteriological studies and wound healing in CLTI with infection, and will be of great help in the future clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To directly compare the clinical outcomes of aortobifemoral bypass surgery (ABF) and endovascular treatment (EVT) for chronic total occlusion (CTO) of the infrarenal abdominal aorta (IAA). Materials and Methods: In this retrospective, multicenter study, we used an international database of 436 patients who underwent revascularization for CTO of the IAA between 2007 and 2017 at 30 Asian cardiovascular centers. After excluding 52 patients who underwent axillobifemoral bypass surgery, 384 patients (139 ABFs and 245 EVTs) were included in the analysis. Propensity score-matched analysis was performed to compare clinical results in the periprocedural period and the long-term. Results: Propensity score matching extracted 88 pairs. Procedure time (ABF; 288 [240–345] minutes vs EVT; 159 [100–205] minutes, p<0.001) and length of hospital stay (17 [12–23] days vs 5 [4–13] days, p<0.001) were significantly shorter in the EVT group than in the ABF group, while the proportions of procedural success (98.9% versus 96.6%, p=0.620), complications (9.1% versus 12.3%, p=0.550), and mortality (2.3% versus 3.8%, p=1.000) were not different between the groups. At 1 months, ABI significantly increased more in the ABF group for both in a limb with the lower (0.56 versus 0.50, p=0.018) and the higher (0.49 versus 0.34, p=0.001) baseline ABI, while the change of the Rutherford category was not significantly different between the groups (p=0.590). At 5 years, compared with the EVT group, the ABF group had significantly better primary patency (89.4±4.3% versus 74.8±4.3%, p=0.035) and survival rates (86.9±4.5% versus 66.2±7.5%, p=0.007). However, there was no significant difference between the groups for secondary patency (100.0%±0.0% versus 93.5%±3.9%, p=0.160) and freedom from target lesion revascularization (TLR) (89.3±4.3% vs 77.3±7.3%, p=0.096). Conclusion: Even with recent advancements in EVT, primary patency was still significantly better for ABF in CTO of the IAA. However, there was no difference between the groups in terms of secondary patency and freedom from TLR at 5 years. Furthermore, there was no difference in procedural success, complications, mortality, and improvement in the Rutherford classification during the periprocedural period, with significantly shorter procedure time and hospital stay in the EVT group. [ABSTRACT FROM AUTHOR]

Brewing yeasts have an essential role in beer production as they convert sugar into ethanol and carbon dioxide and impart flavor to beer during brewing. Brewing yeasts can be classified into the following two types: ale yeast (or top-fermenting yeast; Saccharomyces cerevisiae), which is used for ale-type beer production; lager yeast (or bottom-fermenting yeast; Saccharomyces pastorianus), which is used for lager-type beer production. Globally, approximately 90% of beer is produced using lager yeast. The entire genomes of S. cerevisiae S288C and S. pastorianus Weihenstephan 34/70 were sequenced in 1996 and 2009, respectively. Saccharomyces eubayanus, a parent strain of the lager yeast, was discovered in 2011. These advances have markedly contributed to the studies on brewing characteristics and brewing yeast genes and the rapid development of the field of yeast genetics. To contribute to the development of the beer industry, this review summarizes the genetics of brewer's yeast with a special focus on its genomic structure and the genes involved in brewing characteristics. [ABSTRACT FROM AUTHOR]

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk‐stratification reporting system that was introduced in 2018. The objective of this multi‐institutional study was to evaluate the utility of the MSRSGC in Japan. Methods: In total, 1608 fine‐needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. Results: The cases were classified as follows: nondiagnostic, 18.1%; non‐neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm‐benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non‐neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm‐benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky‐stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non‐neoplastic category. Conclusions: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan. This is the first multi‐institutional study of a large‐scale application of the Milan System for Reporting Salivary Gland Cytopathology in Japan. It demonstrates the usefulness of the Milan system in the diagnosis of salivary gland lesions and for the quality control of salivary gland cytology results. [ABSTRACT FROM AUTHOR]

Background: Androgen receptor signaling inhibitors(ARSIs) have been used to treat patients with metastatic prostate cancer (PC) and castration-resistant prostate cancer (CRPC). In this study, we aimed to identify novel serum extracellular vesicle (EV)-based biomarkers to diagnose ARSI-resistance and therapeutic targets for ARSI-resistant CRPC., Methods: Total RNA contained in serum EVs from 5 cases of CRPC before ARSI treatment and after acquiring ARSI-resistance was subjected to RNA-sequencing. The expression changes of selected RNAs contained in EVs were confirmed in 48 cases of benign prostatic hyperplasia (BPH) and 107 PC using reverse transcription-quantitative PCR (RT-qPCR) and compared with tissue RNA expression using public datasets., Results: RNA-sequencing revealed that mitochondrial oxidative phosphorylation (OXPHOS)-related genes were increased in EVs after acquiring ARSI-resistance. Among them, RT-qPCR and datasets analysis demonstrated that SDHB mRNA was upregulated after acquiring ARSI-resistance in EVs and ARSI-exposed PC tissue compared to ARSI-naïve EVs and tissue, respectively. SDHB mRNA levels both in EVs and tissue were increased in localized PC compared with BPH and decreased in advanced PC. Tissue expression of SDHB mRNA was significantly correlated with those of other OXPHOS-related genes. SDHB mRNA in EVs (EV-SDHB) was elevated among 3 out of 7 ARSI-treating patients with stable PSA levels who later progressed to ARSI-resistant CRPC., Conclusions: The levels of OXPHOS-related mRNAs in EVs correlated with those in PC tissue, among which SDHB mRNA was found to be a novel biomarker to diagnose ARSI-resistance. EV-SDHB may be useful for early diagnosis of ARSI-resistance., (© 2024 Wiley Periodicals LLC.)

This study aimed to compare lower limb events associated with preplanned and finally selected treatment strategies-the validity and usefulness of the physician-chosen strategy were verified.We examined the data of 1003 patients in the registry of multicenter endovascular treatment for superficial femoral and popliteal artery disease study and prospectively enrolled patients who underwent endovascular treatment (EVT) of the femoropopliteal (FP) artery between February 2017 and June 2018 from 67 Japanese institutes. The outcome measures were major adverse limb events (MALE) and target vessel revascularization.The EVT strategies were classified into balloon angioplasty-alone (37.3%), primary stenting (26.7%), and provisional stenting (36.0%) groups. In the initial strategy analysis for the balloon angioplasty-alone, primary stenting, and provisional stenting groups, two-year rates of freedom from MALE (95% confidence interval) were 0.680 (0.620-0.732), 0.754 (0.688-0.808), and 0.798 (0.746-0.840), respectively. Additionally, the rate of MALE was significantly higher among patients in the balloon angioplasty-alone group than among those in the primary or provisional stenting groups in the initial strategy analysis (P = 0.007). Changes in treatment strategy were more frequent in the primary stenting group than in the other groups. Furthermore, the rate of MALE did not significantly differ among the three groups in the final strategy analysis (P = 0.56).Limb outcomes for the final applied strategy did not differ among the three strategies. Additionally, the physician's selection bias was mostly appropriate in the EVT of the FP artery.

A 49-year-old female was incidentally found to have a left renal tumor during a medical check-up. The tumor was too small to be fully diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). Since it was small and showed a homogenous enhancement pattern on contrast-enhanced CT, which made it difficult for us to distinguish the malignancy of the tumor, we performed regular CT follow-up. On the fifth year of her regular follow-up, the tumor had grown apparently larger and showed a heterogenous enhancement pattern, which suggested a malignant tumor. Since the tumor was exophytic, we decided to perform a laparoscopic partial nephrectomy. The operation was performed without any serious complications, and her renal function remained unchanged. The histopathology of the tumor was leiomyoma. Here, we discuss the characteristics of this tumor and the role of immunohistopathology in the diagnosis.

Background/aim: We aimed to evaluate the changes of androgen receptor (AR) signaling-related long non-coding RNAs (lncRNAs) in serum extracellular vesicles (EVs) from prostate cancer (PC) patients, in order to identify novel biomarkers for AR axis-targeted therapy (ARAT)-resistance among castration-resistant PC (CRPC) patients., Patients and Methods: EVs were isolated from 2 patients before and after acquiring ARAT-resistance. RNA profiling of EVs was performed by RNA-sequencing. The expression levels of selected lncRNAs in EVs were analyzed by digital droplet PCR (ddPCR) in 58 localized and 14 metastatic PC patients at diagnosis, 7 ARAT-naïve and 6 ARAT-resistant CRPC patients. LncRNA H19 expression in PC tissue was examined using published data. In order to analyze the role of H19, the prognosis was analyzed in PC patients and proteomic analysis was performed in 22Rv1 PC cells., Results: RNA-sequencing revealed that AR-regulated RNAs were most enriched in EVs after acquiring ARAT-resistance. Among them, up-regulation of AR signaling-related lncRNAs (PCAT1, H19, HOXA-11AS, ZEB1-AS1, ARLNC1, PART1, CTBP1-AS and PCA3) was confirmed by ddPCR. H19 contained in EVs (EV-H19) was significantly increased among ARAT-resistant patients compared to ARAT-naïve CRPC or metastatic PC patients. In PC tissue, H19 was negatively correlated with AR protein and AR-activity score and up-regulated in neuroendocrine CRPC tissue with low AR expression. Furthermore, EV-H19 expression was significantly associated with worse outcome to androgen-deprivation therapy. Proteomic analysis demonstrated that H19 knockdown enhanced PC-related protein expression., Conclusion: EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To assess wound healing after simultaneous endovascular treatment (EVT) and minor forefoot amputation and identify the predictors of delayed wound healing in patients with chronic limb-threatening ischemia (CLTI) and bacterial infections of the wounds., Methods: In this single-center retrospective cohort study, we evaluated 79 consecutive limbs with tissue loss from 73 CLTI patients who underwent simultaneous EVT and minor forefoot amputation between November 2017 and May 2020. To estimate the rate of wound healing after the simultaneous procedure, we used the Kaplan-Meier method. To assess the association between baseline characteristics and delayed wound healing, we used the Cox proportional hazard model., Results: All patients who underwent the simultaneous procedure had ischemic wounds with bacterial infection. The rate of wound healing at 6 months reached 82%. The median time for wound healing was 76 days. According to multivariable analysis, Lisfranc/Chopart amputation (hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.09-6.60), absence of above-the-knee (ATK) occlusive lesions (HR 1.89, 95% CI 1.04-3.45), and poor below-the-ankle (BTA) runoff (HR 1.77, 95% CI 1.01-3.11) were independent predictors of delayed wound healing., Conclusion: Lisfranc/Chopart amputation, absence of ATK occlusive lesions, and poor BTA runoff were independent predictors of delayed wound healing after simultaneous EVT and minor forefoot amputation in patients with CLTI and bacterial infections of the wound.

Background/aim: Cancer cells with high anchorage independence can survive and proliferate in the absence of adhesion to the extracellular matrix. Under anchorage-independent conditions, cancer cells adhere to each other and form aggregates to overcome various stresses. In this study, we investigated the cytomorphology and gene expression signatures of oral cancer cell aggregates., Materials and Methods: Two oral cancer-derived cell lines, SAS and HSC-3 cells, were cultured in a low-attachment plate and their cytomorphologies were observed. The transcriptome between attached and detached SAS cells was examined using gene expression microarrays. Subsequently, gene enrichment analysis and Ingenuity Pathway Analysis were performed. Gene expression changes under attached, detached, and re-attached conditions were measured via RT-qPCR., Results: While SAS cells formed multiple round-shaped aggregates, HSC-3 cells, which had lower anchorage independence, did not form aggregates efficiently. Each SAS cell in the aggregate was linked by desmosomes and tight junctions. Comparative transcriptomic analysis revealed 1,698 differentially expressed genes (DEGs) between attached and detached SAS cells. The DEGs were associated with various functions and processes, including cell adhesion. Moreover, under the detached condition, the expression of some epithelial genes (DSC3, DSP, CLDN1 and OCLN) were up-regulated. The changes in both cytomorphology and epithelial gene expression under the detached condition overall returned to their original ones when cells re-attached., Conclusion: The results suggest specific cytomorphological and gene expression changes in oral cancer cell aggregates. Our findings provide insights into the mechanisms underlying anchorage-independent oral cancer cell aggregation and reveal previously unknown potential diagnostic and therapeutic molecules., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: De-differentiation is a key step for the progression of cancer cells. This study investigated the anti-tumor effect of kartogenin (KGN), which has the ability to differentiate cells, on prostate cancer (PC) cells., Materials and Methods: The effects of KGN on androgen receptor (AR) nuclear localization, prostate-specific antigen (PSA) expression, and Smad2 activation as well as the growth of PC cell lines (LNCaP, 22Rv1 and PC-3) were analyzed., Results: KGN significantly inhibited growth of AR-expressing LNCaP and 22Rv1 cells but not of AR-lacking PC-3 cells. KGN decreased AR nuclear localization and PSA expression, but did not enhance the anti-tumor effect of bicalutamide in LNCaP cells. KGN activated Smad2 both in the absence and presence of TGF-β1. KGN also inhibited growth of docetaxel-resistant PC cells, 22Rv1DR, and re-sensitized them to the agent., Conclusion: KGN has a potential as a novel therapeutic for PC patients after treatment failure., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)