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Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III-V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

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.)

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction ( n  = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80 + M1, CD206 + M2 (anti-inflammatory macrophages), PDGFRα + MSC, and TNF-α + cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n  = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm 3 vs 0.02 mm 3 , p <.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p <.0001). Clodronate group showed significant reduction in mean number of CD80 + , TNF-α + , PDGFRα + , and CD80 + TNF-α + cells on day 5 (306.5 vs 558.8, p <.0001; 280.5 vs 543.8, p <.0001; 365.0 vs 633.0, p <.0001, 29.0 vs 42.5, p <.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p =.0004; 479.3 vs 384.5, p =.0008; 593.0 vs 473.0, p =.0010, 41.0 vs 32.5, p =.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e , Gbp6 , and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

Objective: The present study investigated the prognostic factors for follicular thyroid carcinoma (FTC) with the incorporation of the histologic subtype and degree of vascular invasion (VI)., Patients: The records of 474 patients with FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were reviewed in this retrospective cohort study. The Cox proportional hazard model was used to determine factors associated with disease-free survival (DFS) and distant metastasis-free survival., Results: Of the 474 patients, 140 (30%) had minimally invasive FTC, 260 (55%) had encapsulated angio-invasive FTC, and 74 (16%) had widely invasive FTC. Among the 428 patients with M0 FTC, the 10-year DFS rates of patients with minimally invasive FTC (n = 133), encapsulated angio-invasive FTC (n = 247), and widely invasive FTC (n = 48) were 97.3%, 84.2%, and 69.9% (P < .001), respectively. A multivariate analysis identified aged ≥55 years (hazard ratio [HR], 2.204; 95% CI, 1.223-3.969; P = .009), histologic subtype (HR, 2.068; 95% CI, 1.064-4.021; P = .032), VI of ≥2 (HR, 6.814; 95% CI, 3.157-14.710; P < .001), and tumor size >40 mm (HR, 2.014; 95% CI, 1.089-3.727; P = .026) as independent negative prognostic factors for DFS., Conclusion: Our study results may enable us to stratify the prognosis of FTC more accurately by combining the histologic subtype with the degree of VI ≥2, aged ≥55 years, and tumor size >40 mm., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polyethylene (PE), a widely used recalcitrant synthetic polymer, is a major global pollutant. PE has very low biodegradability due to its rigid C-C backbone and high hydrophobicity. Although microorganisms have been suggested to possess PE-degrading enzymes, our understanding of the PE biodegradation process and its overall applicability is still lacking. In the present study, we used an artificial bacterial consortium for PE biodegradation to compensate for the enzyme availability and metabolic capabilities of individual bacterial strains. Consortium members were selected based on available literature and preliminary screening for PE-degrading enzymes, including laccases, lipases, esterases, and alkane hydroxylases. PE pellets were incubated with the consortium for 200 days. A next-generation sequencing ana-lysis of the consortium community of the culture broth and on the PE pellet identified Rhodococcus as the dominant bacteria. Among the Rhodococcus strains in the consortium, Rhodococcus erythropolis was predominant. Scanning electron microscopy (SEM) revealed multilayered biofilms with bacteria embedded on the PE surface. SEM micrographs of PE pellets after biofilm removal showed bacterial pitting and surface deterioration. Multicellular biofilm structures and surface biodeterioration were observed in an incubation of PE pellets with R. erythropolis alone. The present study demonstrated that PE may be biodegraded by an artificially constructed bacterial consortium, in which R. erythropolis has emerged as an important player. The results showing the robust colonization of hydrophobic PE by R. erythropolis and that it naturally possesses and extracellularly expresses several target enzymes suggest its potential as a host for further improved PE biodeterioration by genetic engineering technology using a well-studied host-vector system.

Purpose: Lenvatinib (LEN) is a multikinase inhibitor that strongly inhibits tyrosine kinase receptors, especially VEGFR-2, which can cause hypertension, as well as strong tumor shrinkage. Though control of any side effects (SEs) is important for maintaining dose intensity (DI), hypertension is particularly important, because blood pressure (BP) can change quickly and respond to LEN administration and withdrawal, and it can be controlled with antihypertensive medications. Focusing on the early phase of treatment, the effect of BP 8 weeks after LEN initiation (BP 8w ) on DI at 8 weeks (DI 8w ) was investigated., Methods: The subjects were 85 thyroid cancer patients who started LEN at 24 mg/day and continued for ≥8 weeks. The BP at the start of LEN (BP base ), BP 8w grade, and DI 8w were examined., Results: Median (range) systolic BP changed significantly from BP base of 117 (84-167) mmHg to BP 8w of 134 (103-168) mmHg (p<0.001). Antihypertensive treatment at baseline, systolic BP base , and male sex were related to higher DI 8w on multivariate analysis. The median DI 8w of the 23 patients who required dose modification due to hypertension was 20.2 mg/day (n=6) in grade 1, 15.8 mg/day (n=13) in grade 2, and 14.5 mg/day (n=4) in grade 3, showing a trend toward lower DI 8w as the grade level increased., Conclusion: LEN can increase BP by 20 mmHg at 8 weeks even with intensive antihypertensive management. Baseline antihypertensive treatment and BP base can affect DI 8w . A higher DI 8w may be achieved by aiming for a low 8-week BP with more intensive antihypertensive therapy after LEN initiation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to investigate the association between the extent of vascular invasion (VI) and the outcome of widely invasive follicular thyroid carcinoma (WI-FTC)., Methods: The records of 107 patients with WI-FTC confirmed by surgical specimens from January 2005 to December 2016 were retrospectively reviewed., Results: Among the 107 patients with WI-FTC, those with a VI of < 4 (n = 62) and ≥ 4 (n = 45) had a 10 year cause-specific survival (CSS) rate of 97.7% and 89.4% (p = 0.008), respectively. Univariate analysis identified M1 (p = 0.001), and the number of VI of ≥ 4 as significant negative prognostic factors for CSS. Multivariate analysis identified M1 (hazard ratio [HR] = 9.366) as independent negative prognostic factor for CSS. Among the 72 patients with M0 WI-FTC, those with a VI of < 2 (n = 33) and ≥ 2 (n = 39) had a 10-year distant metastasis-free survival (DMFS) rate of 96.8% and 56.8% (p = 0.001), respectively. Univariate analysis identified age ≥ 55 years (p = 0.011), presence of VI, the number of VI of ≥ 2, and resection margin status (p < 0.001) as significant negative prognostic factors for DMFS. Multivariate analysis identified the number of VI ≥ 2 (HR = 9.137), and resection margin status (HR = 5.853) as independent negative prognostic factors for DMFS., Conclusions: It may be unnecessary that WI-FTC with curative resection margin status and a VI of < 2, especially in capsular invasion only, routinely undergo completion thyroidectomy and postoperative ablation., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: The application of intraoperative neurophysiological monitoring (IONM) has been accepted to avoid injury of a recurrent laryngeal nerve (RLN). Loss of the neuromonitoring signal indicates nerve injury and is subdivided into segmental type and global type nerve paralysis. This study aimed to determine the course of vocal cord function recovery after definitive loss of signal (LOS) types., Methods: This retrospective study included 1,442 patients (with 2,752 nerves at risk) who had thyroidectomies between January 2018 and December 2021. Preoperative and postoperative vocal cord functions were evaluated by laryngoscopic examination., Results: LOS occurred in 168 of 1,442 (11.7%) patients and 171 of 2,748 (6.2%) nerves at risk during surgery. Of LOS nerves of benign tumors, 74.2% showed global type. In cancer cases, segmental paralysis was more common, accounting for 51.3% of LOS nerves. Of nerves with segmental LOS in cancer patients, 55.3% needed partial layer resection for RLN invasion. Intraoperative recovery was seen in 9 of 62 nerves (14.5%) with segmental LOS and 32 of 109 (29.4%) nerves with global type LOS. The vocal cord palsy rate on postoperative days (PODs) 2-3 was lower after global type nerve paralysis (63.6%) than after segmental loss (84.9%). At 6 months postoperatively, the rate of vocal cord paralysis in benign tumors was not significantly different between segmental type and global type (P=0.586). However, cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively (rate of nerve palsy: segmental 40.0% vs . global 3.4%) (P<0.001)., Conclusions: The intraoperative recovery rate and early nerve recovery rate are significantly higher for patients with global LOS than for patients with segmental LOS. Cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-149/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

The Comamonadaceae bacterial strains OS-1 and OS-4 were isolated from pond water and were found to be highly sensitive to hydrogen peroxide in the agar plates. Here, we report the nearly complete and complete genome sequences, respectively, of these two strains.

Background: Age has been recognized as one of the strong prognostic indicators for thyroid cancer. However, treatment strategies for papillary thyroid cancer (PTC) are usually determined only by the extent of disease progression, without considering the patient's age. The aim of this study was to investigate how the surgical strategy for PTC should take into account patient age., Methods: To exclude the effect of treatment strategy, 837 patients treated with uniform treatment strategies (hemithyroidectomy without radioiodine therapy) between 1986 and 1995 were the subjects of this study. Using a Cox proportional hazard model, clinical risk factors related to disease-specific survival (DSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were analyzed. A receiver-operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff points., Results: Significant risk factors related to DSS and DMFS were age, extrathyroidal extension (ETE), and numbers of metastatic lymph nodes (NMLNs), but age was not significantly related to DFS. The 20-year DSS and DMFS rates were fair in patients without ETE regardless of age or NMLNs. However, in patients with ETE, DSS and DMFS rates were significantly worse in elderly patients than in young patients. ROC curve analysis showed that the optimal cutoff age was 48 years for discriminating DSS in patients with ETE., Conclusion: Regardless of age, PTC patients without ETE are candidates for a treatment strategy not using RAI, and more aggressive treatment may be recommended for elderly PTC patients with ETE., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Purposes: To establish the appropriate staging system and assess the role of curative thyroidectomy alone (Surgery) vs. involved-site radiation therapy after open biopsy (OB-ISRT) in stage IE mucosa-associated lymphoid tissue (MALT) lymphoma., Methods: We examined the Tokyo Classification as a modified classification. This retrospective cohort study included 256 patients with thyroid MALT lymphoma; 137 underwent standard therapy (i.e., OB-ISRT) and were enrolled for the Tokyo classification. Sixty stage IE patients with the same diagnosis were examined to compare Surgery with OB-ISRT., Results: Overall survival ( p = 0.0092) and relapse-free survival (0.00113) were significantly better in stage IE vs. stage IIE under the Tokyo classification. No OB-ISRT and Surgery patients died, but three OB-ISRT patients relapsed. The incidence of permanent complications was 28% in OB-ISRT (mainly dry mouth) and 0% in Surgery ( p = 0.027). The number of painkiller prescription days was significantly greater in OB-ISRT ( p < 0.001). During follow-up, the rate of the new appearance/change of the low-density area in the thyroid gland was significantly higher in OB-ISRT ( p = 0.031)., Conclusions: The Tokyo classification allows an appropriate discrimination between stages IE and IIE MALT lymphoma. Surgery can provide a good prognosis in stage IE cases; it also avoids complications, shortens painful periods during treatment, and simplifies ultrasound follow-up.

Purpose: The purpose of this study was to examine the postoperative clinical course of parathyroid carcinoma to determine factors that predict postoperative recurrence and distant metastasis., Methods: In this retrospective study, we included 38 patients with parathyroid carcinoma who received surgical intervention at Itoh Hospital between 1979 and 2020. Clinicopathologic characteristics (age, sex, intact PTH, serum Ca level, operation type, parathyroid weight, parathyroid size, histopathologic findings: vascular invasion, capsular invasion, necrosis, histological type, and Ki-67 staining) were used. The median follow-up observation period was 63.7 months., Results: Postoperatively, 5 patients (13.2%) developed distant metastasis or had localized recurrence, and 3 patients died (7.9%). The results of the univariate analysis revealed three factors affecting distant metastasis and recurrence, which were Ki-67 (p = 0.0041), the presence or absence of necrosis (p = 0.0163), and tumor weight (p = 00,189). Using the cutoff values obtained by ROC analysis, which were 4.1 for Ki-67 (sensitivity of 80% and specificity of 96.9%) and 4890 mg for tumor weight (sensitivity of 100% and specificity of 60.9%), we calculated the cumulative incidence of recurrence and distant metastasis by the three factors retained. We found that the presence of the three factors was associated with a high possibility of distant metastasis or recurrence during the 5-year follow-up period., Conclusions: Three factors, Ki-67, necrosis, and tumor weight in parathyroid carcinoma, may predict outcomes of postoperative recurrence and distant metastasis., (© 2023. The Author(s).)

The clinical utilities of paclitaxel in anaplastic thyroid carcinoma (ATC) have been reported. The current study investigated the outcomes in ATC patients treated by paclitaxel as neoadjuvant setting. Furthermore, the prognostic factor for overall survival (OS) and predictive marker for response to paclitaxel were investigated. Records of ATC patients treated by paclitaxel as neoadjuvant setting in our hospital were reviewed. The median OS for the patients with (n = 43) and without (n = 23) resection were 14.7 (95% CI, 11.0-21.7) and 4.2 (95% CI, 3.0-5.4) months, respectively (p < 0.001). Univariate analysis identified the factors of stage (p = 0.028), prognostic index (PI) ≥2 (p < 0.001), response to paclitaxel (p = 0.007), resection (p < 0.001), and radiotherapy (p < 0.001) to be associated with OS, and multivariate analysis revealed that the factors of PI ≥2 [hazard ratio (HR), 2.406 (95% CI, 1.096-5.281), p = 0.029], response to paclitaxel [HR, 0.423 (95% CI, 0.193-0.930), p = 0.032], resection [HR, 0.316 (95% CI, 0.129-0.773), p = 0.012], and radiotherapy [HR, 0.229 (95% CI, 0.100-0.526), p < 0.001] were independent prognostic factors of OS. There were no significant predictive factors for response to paclitaxel in baseline characteristics. PI ≥2, response to paclitaxel, resection, and radiotherapy were independent prognostic factors in ATC patients treated with paclitaxel as neoadjuvant setting. It is important to investigate predictor for response to paclitaxel for improving resectability and prognosis in ATC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Rhodococcus has been extensively studied for its excellent ability to degrade artificial chemicals and its capability to synthesize biosurfactants and antibiotics. In recent years, studies have attempted to use Rhodococcus as a gene expression host. Various genetic tools, such as plasmid vectors, transposon mutagenesis, and gene disruption methods have been developed for use in Rhodococcus ; however, no effective method has been reported for performing large-size genome reduction. Therefore, the present study developed an effective plasmid-curing method using the levansucrase-encoding sacB gene and a simple two-step genome-reduction method using a modified Cre/ loxP system. For the results, R. erythropolis JCM 2895 was used as the model; a mutant strain that cured all four plasmids and deleted seven chromosomal regions was successfully obtained in this study. The total DNA deletion size was >600 kb, which corresponds mostly to 10% of the genome size. Using this method, a genome-structure-stabilized and unfavorable gene/function-lacking host strain can be created in Rhodococcus . This genetic tool will help develop and improve Rhodococcus strains for various industrial and environmental applications.

The effects of soluble and insoluble lanthanides on gene expression in Methylococcus capsulatus Bath were investigated. Genes for lanthanide-containing methanol dehydrogenases (XoxF-MDHs) and their calcium-containing counterparts (MxaFI-MDHs) were up- and down-regulated, respectively, by supplementation with soluble lanthanide chlorides, indicating that M. capsulatus has the "lanthanide switch" observed in other methanotrophs. Insoluble lanthanide oxides also induced the lanthanide switch and were dissolved by the spent medium of M. capsulatus, suggesting the presence of lanthanide-chelating compounds. A transcriptome ana-lysis indicated that a gene cluster for the synthesis of an enterobactin-like metal chelator contributed to the dissolution of insoluble lanthanides.

Hydrogen peroxide (H 2 O 2 ) inhibits microbial growth at a specific concentration. However, we previously isolated two environmental bacterial strains that exhibited sensitivity to a lower H 2 O 2 concentration in agar plates. Putative catalase genes, which degrade H 2 O 2 , were detected in their genomes. We herein elucidated the characteristics of these putative genes and their products using a self-cloning technique. The products of the cloned genes were identified as functional catalases. The up-regulation of their expression increased the colony-forming ability of host cells under H 2 O 2 pressure. The present results demonstrated high sensitivity to H 2 O 2 even in microbes possessing functional catalase genes.

We previously showed that autoclaving in preparing agar media is one of the sources of hydrogen peroxide (H 2 O 2 ) in the medium. This medium-embedded H 2 O 2 was shown to lower the total colony count of environmental microorganisms. However, the critical concentrations of H 2 O 2 detrimental to colony formation on the agar plate remain largely undetermined. Herein, we elucidated the specific effect of H 2 O 2 on microbial colony formation on solid agar medium by external supplementation of varying amounts of H 2 O 2 . While common laboratory strains (often called domesticated microbes) formed colonies in the presence of high H 2 O 2 concentrations (48.8 μM or higher), microbes from a freshwater sample demonstrated greatly decreased colony counts in the presence of 8.3 μM H 2 O 2 . This implies that environmental microbes are susceptible to much lower concentrations of H 2 O 2 than laboratory strains. Among the emergent colonies on agar plates supplemented with different H 2 O 2 concentrations, the relative abundance of betaproteobacterial colonies was found to be lower on plates containing higher amounts of H 2 O 2 . Further, the growth of the representative betaproteobacterial isolates was completely inhibited in the presence of 7.2 μM H 2 O 2 . Therefore, our study clearly demonstrates that low micromolar levels of H 2 O 2 in agar plates critically affect growth of environmental microbes, and large portions of those are far more susceptible to the same than laboratory strains. IMPORTANCE It is well-known that most of environmental microorganisms do not form colonies on agar medium despite that agar medium is the commonly used solidified medium. We previously demonstrated the negative effects of H 2 O 2 generation during agar medium preparation on colony formation. In the present study, we investigated the independent effect of H 2 O 2 on microbial growth by adding different concentrations of H 2 O 2 to agar medium. Our results demonstrate for the first time that even low micromolar levels of H 2 O 2 in agar plates, that are far lower than previously recognized as significant, adversely affect colony number obtained from freshwater inoculum.

The complete genome sequence of Rhodococcus erythropolis JCM 2895, an antibiotic protein-producing strain, was determined. It consists of a 6,455,263-bp chromosome, one linear plasmid (pR09L01 [227,989 bp]), and three circular plasmids (pR09C01 [79,600 bp], pREC01 [5,420 bp], and pREC02 [5,444 bp]).

Background: The present study investigated the association between local resection and cause of death in anaplastic thyroid carcinoma (ATC) patients with stage IVC disease., Methods: A total of 54 ATC patients with stage IVC disease were included in the study. Information including patient characteristics, laboratory data including complete blood count, treatment, and death were collected for analysis., Results: The median overall survival (OS) for patients with or without resection was 8.4 [95% confidence interval (CI) 5.9-14.4)] and 4.2 (95% CI 2.5-6.2) months, respectively (p < 0.001). No patients survived without resection at 1 year. Univariate analysis revealed that resection (p < 0.001) and radiotherapy (p = 0.018) were significantly associated with OS. Multivariate analysis revealed that resection (hazard ratio 0.257; 95% CI 0.115-0.575; p < 0.001) was the only independent prognostic factor of OS. In ATC patients with known resection status, the median OS for the patients with a resection status of R0/1 (n = 28) and R2 (n = 7) were 13.0 (95% CI 7.5-18.7) and 1.7 (95% CI 0.1-6.2) months, respectively (p < 0.001). The most common specific cause of death was respiratory insufficiency (35%), followed by airway obstruction (25%) and cerebral cardiovascular-related death (5%). The frequency of airway obstruction was significantly lower in patients with resection (p = 0.018)., Conclusions: Resection probably impacts on clinical course in ATC patients despite the presence of distant metastasis. However, R2 resection is likely to be harmful and surgeons should carefully consider the resectability of thyroid tumors., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background and Objectives: Tyrosine kinase inhibitors (TKIs) have provided excellent clinical benefits to patients with advanced differentiated thyroid cancer (DTC): however, the tumor status for which maximum efficacy can be obtained remains controversial. We conducted this study to identify effective clinical predictors, focusing on disease progression., Methods: Using the data of 42 DTC patients treated with lenvatinib, we investigated the clinical factors related to overall survival (OS) and progression-free survival (PFS), and conducted analyses by the scoring of the factors., Results: The 3 year OS and median PFS were 51% and 13.8 months, respectively. Univariate analysis identified performance status (PS), tumor-related symptoms, and tumor diameter as the only factors affecting both these outcomes. Giving 1-point for each of these three factors, a higher score was significantly related to shorter OS and PFS. Patients with two or fewer points (n = 34) had better median OS (NR vs 3.9 months, p < 0.001) and PFS (15.7 vs 2.1 months, p < 0.001) than patients with three points (n = 8). Patients with all three factors had a significantly worse prognosis than patients with two or fewer factors., Conclusion: DTC patients with all three indicators are unlikely to have longer survival. Therefore, it is important to commence TKIs before disease progression., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Lenvatinib is started at a standard dose, continuing with dose reduction and interruption, balancing between efficacy and adverse events (AEs). Because few drugs are available for thyroid cancer, efforts for continuing treatment with one agent, such as "dose escalation (DE)", are made. The dose is increased, aiming to regain the anti-tumor effect after dose reduction. The effects of lenvatinib DE in differentiated thyroid carcinoma (DTC) patients are reported., Patients and Methods: The efficacy of lenvatinib DE in DTC patients using the serum thyroglobulin (Tg) level and management of AEs was investigated., Results: A total of 70 DE episodes in 33 patients were investigated. The median increased dose was 2.0 (1.0-14.0) mg, increased from 8.6 (2-16) mg to 10.1 (6-24) mg. The serum Tg level decreased in 53 DE episodes. Though the serum Tg level in 17 DE episodes was not decreased, the Tg rate of increase was decreased in 7 of these DE episodes using the Tg-doubling rate. Overall, clinical benefit was seen in 60 (86%) DE episodes. AEs that could not be controlled after DEs were seen in only 16% of cases. No intolerable AEs were observed in patients who received more drug holidays at the time of DEs compared to two times before the DEs., Conclusion: DE may become one of the standard treatment strategies after disease progression if AEs are well managed. Drug holidays may be a key for successfully controlling AEs with DE. DE can be useful for controlling progressive disease with increasing Tg levels., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism., Design: This was a retrospective study., Methods: Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed., Results: Preoperative intact-parathyroid hormone (P = 0.0003), serum calcium (P = 0.0048), and tumor diameter (P = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased., Conclusion: In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.

Gentamicin is an important antibiotic for the treatment of opportunistic infections in the clinical field. Gentamicin-resistant bacteria have been detected in livestock animals and can be transmitted to humans through the food supply or direct contact. We have previously revealed that gentamicin-resistant Escherichia coli are distributed at a comparatively high rate from beef cattle in Japan, but few studies have focused on the molecular epidemiology of gentamicin-resistant bacteria. To understand these bacteria, this study examined the prevalence of various gentamicin resistance genes in gentamicin-resistant E. coli isolates from beef cattle feces. Of the 239 gentamicin-resistant E. coli isolates, the presence of the aacC2, aadB, or aac(3)-VIa genes was confirmed in 147, 84, and 8 isolates, respectively. All aac(3)-VIa-harboring isolates had an MIC value of 64 μg/mL for gentamicin and exhibited resistance to 11 antibiotic agents. An analysis of the representative aac(3)-VIa-harboring E. coli strain GC1-3-GR-4 revealed that the aac(3)-VIa gene was present on the IncA/C plasmid together with the aadA and bla CMY genes. Furthermore, the upstream region of the aac(3)-VIa gene contained the aadA gene and the class 1 integron-integrase gene (intI1). The aac(3)-VIa gene was detected for the first time in Japan and is expected to be able to transfer between bacteria via the IncA/C plasmid and integron. These results reveal the expansion of the distribution or diversity of gentamicin resistance genes in Japan., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: There is no sufficient data about the clinical course and outcome in thyroid cancer patients who become pregnant after diagnosis of distant metastasis (DM). The current study was conducted to collect information regarding the clinical and reproductive characteristics, and outcomes in thyroid cancer patients who became pregnant after being diagnosed with DM., Methods: Records of 125 differentiated thyroid cancer (DTC) patients with age ≤45 years at DM diagnosis who had visited Ito Hospital from January 2005 to June 2021 were retrospectively reviewed. Among those 125 patients, 28 who became pregnant after DM diagnosis were classified as pregnancy group, and the remained 97 patients were classified as comparator group., Results: In pregnancy group, the median age at malignancy diagnosis, DM diagnosis, and first pregnancy after DM diagnosis was 25 years (range, 4-41 years), 27 years (range, 11-41 years), and 32 years (range, 25-45 years), respectively. Fifty-five pregnancies and 40 live births were reported. Other pregnancy outcomes were miscarriage (n = 14) and induced abortion (n = 1). The 10-year progression-free survival (PFS) rates of pregnant and comparator group were 92.1% and 74.4%, respectively (p = 0.018). The multivariate analysis showed that multiple 131 I treatment was independent negative prognostic factor for PFS (p = 0.046)., Conclusions: DTC patients with age ≤45 years at DM diagnosis had good survival even though they became pregnant. Our results add to the information required for counseling thyroid cancer patients who have concerns about their fertility in the future., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previous studies have reported an association between four or more foci of vascular invasion (VI) and thyroid cancer prognosis, while the current study aimed to investigate the association between extent of VI and outcome of encapsulated angioinvasive follicular thyroid carcinoma (FTC)., Methods: The records of 303 patients with encapsulated angioinvasive FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were retrospectively reviewed. Thirteen patients had distant metastasis at diagnosis and were classified as M1., Results: Among the 290 patients with M0 encapsulated angioinvasive FTC, the 10-year disease-free survival (DFS) rate was 85.6%. Those with a VI of 1 (n = 131) or ≥ 2 (n = 159) had a 10-year DFS rate of 94.9% and 77.9% (p < 0.001), respectively, and those with a VI of 1-3 (n = 211) or ≥ 4 (n = 79) had a 10-year DFS rate of 86.3% and 83.3% (p = 0.311), respectively. Multivariate analysis identified age ≥ 55 years (p = 0.031) and VI ≥ 2 (p = 0.002) as independent negative prognostic factors for DFS. Patients with M0 encapsulated angioinvasive FTC aged ≥ 55 years and VI ≥ 2 had significantly poorer prognosis and a 10-year DFS rate of 66.4% (p < 0.001)., Conclusions: Patients with encapsulated angioinvasive FTC who had two or more foci of VI, especially patients aged ≥ 55 years, should be carefully followed-up., (© 2022. Society of Surgical Oncology.)

Background: The characteristics of pediatric differentiated thyroid cancer (DTC) are substantially different from those of adult DTC. This study investigated whether the cutoff age of 18 years, as recommended by the American Thyroid Association (ATA) management guidelines for pediatric DTC, is appropriate based on clinical characteristics and outcomes. Methods: The medical records of 288 patients aged <21 years with DTC, who underwent initial surgery between 1979 and 2014, were retrospectively reviewed. Disease-free survival (DFS) rates and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method. As per the International Incidence of Childhood Cancer Report and the ATA management guidelines, cutoff ages of 14 and 18 years were analyzed in this study. Results: The age distributions of the subjects were as follows: 53 patients were aged <15 years (18.4%), 118 patients were aged 15-18 years (41%), and 117 patients were aged 19-20 years (40.6%). The DMFS rates were significantly different between the two cutoff ages. The DMFS was also significantly different between patients aged >15 years and patients aged 15-18 years; however, no significant difference was observed between patients aged 15-18 and 19-20 years. Multivariate analyses showed that clinically apparent lymph node metastasis (cN1) and gross extrathyroidal extension were significant factors related to DFS and DMFS. Although age as a continuous variant was not a significant factor related to either DFS or DMFS, when the cutoff age was set as 14 years rather than 18 years, differences in patient characteristics related to DMFS and DFS stood out. Conclusions: This study found that age was not significantly related to clinical outcome. However, in the younger patient group, more patients had factors that related to DFS and DMFS. Due to the indolent biological behavior of DTC, age at presentation or thyroidectomy does not always represent the age at occurrence, but patients aged <15 years had distinct clinical manifestations. Age <15 years rather than <19 years may therefore be a more suitable cutoff age in pediatric DTC.