Outcomes of sentinel node biopsy according to MRI response in an association with the subtypes in cN1-3 breast cancer after neoadjuvant systemic therapy, multicenter cohort study.

BACKGROUND: This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. METHODS: In the multicenter retrospective cohort, 388 individuals with cN1-3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST. RESULTS: In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2- (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6-54.0] and 20.9% [95% CI 14.1-27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0-0), whereas that of non-complete responders was 33.3% (95% CI 20.8-45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0-16.7). CONCLUSIONS: Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.

Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy.

INTRODUCTION: The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST. METHODS: This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model. RESULTS: Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%). CONCLUSIONS: SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.

Novel radiologic indices for stem type decision in total hip arthroplasty in patients with metaphyseo-diaphyseal mismatched Dorr A proximal femur.

BACKGROUND: In metaphyseo-diaphyseal (M-D) mismatched Dorr A femurs, it is difficult to achieve proper fixation with a type 1 stem. Proper interpretation of the geometry of the femur is integral at the preoperative stage in an M-D mismatched femur, but there has been a scarcity of studies on the radiologic indices. Therefore, we analyze the previous radiologic indices and suggest the novel ones for M-D mismatched femurs. METHODS: Our study was a retrospective review of preoperative radiographs of patients who underwent total hip arthroplasty with the smallest type 1 stem or with type 3 C stem at a single institution from July 2014 to March 2022. A Type 3 C stem was used when the smallest type 1 stem failed to achieve metaphyseal fixation. One hundred twenty-six patients were categorized into two main groups. Canal-flare index, canal-calcar ratio, modified morphological cortical index, and two novel indices (lesser trochanter-to-distal ratio-α and -ß [LDR-α and -ß]) were assessed on preoperative pelvic radiographs. RESULTS: Multivariate and ROC analysis demonstrated that high LDR-ß (Exp[B]: 485.51, CI: 36.67-6427.97, p < 0.001) was associated with a more mismatched tendency group and had clinically acceptable discriminatory power (AUC: 0.765, CI: 0.675-0.855, p < 0.001) between the two cohorts. CONCLUSION: Correct assessment of preoperative femoral morphology would be fundamental in the selection of a suitable stem. The ratio based on 3 cm below the lesser trochanter of the femur seemed crucial. We recommend evaluating the newly described radiological index preoperatively in M-D mismatched Dorr A femur for planning precisely and selecting a proper stem.

Comparison of specificity and sensitivity of diagnostic methods for Enteromyxum leei and Enteromyxum fugu detected from cultured tiger puffer, Takifugu rubripes in Korea.

Enteromyxum leei and Enteromyxum fugu, which are myxosporean parasites, were first found in cultured tiger puffer Takifugu rubripes in Korea. We collected four tiger puffers that showed severe emaciation signs for our experiments. DNA sequencing was confirmed that the tiger puffers were coinfected with E. leei and E. fugu. Furthermore, similar amounts of E. leei and E. fugu were confirmed using real-time PCR in the intestine. To the best of our knowledge, there have been no reports of E. fugu infection in the olive flounder Paralichthys olivaceus. However, the diagnosis of inflowing water, discharged water and olive flounder samples using highly sensitive diagnostic methods confirmed the presence of E. fugu in water and fish samples from olive flounder farms near the tiger puffer farm. Therefore, the present study aimed to develop highly sensitive diagnostic methods such as real-time and two-step PCR for early diagnosis and follow-up of the emaciation disease and multiplex PCR for rapid diagnosis. The multiplex PCR method exhibited the same sensitivity as the one-step PCR method developed in this study, demonstrating its efficacy for rapid diagnosis. Therefore, the suggested methods can be utilized for the early diagnosis and rapid diagnosis of emaciation diseases and reduction of economic losses through rapid disease control.

Computed Tomography Evaluation of Alumina Ceramic-on-Ceramic Total Hip Arthroplasty With More Than 20 years of Follow-Up: Is a Follow-Up Computed Tomography Scan Necessary?

BACKGROUND: Ceramic-on-ceramic (CoC) bearings have been increasingly used in total hip arthroplasty (THA) because of their superior wear resistance and biocompatibility. However, there is a scarcity of reports on the computed tomography (CT) evaluation of CoC bearings with more than 10 years. The aim of this study was to evaluate the long-term CT results of THA using CoC bearings for more than 20 years of follow-up. We hypothesized that there would be no wear, osteolysis, or ceramic fracture. METHODS: Between November 1997 and June 2003, 956 hips underwent THA using alumina-on-alumina bearings at a tertiary referral hospital. Among them, 107 hips were assessed, all of which underwent a CT examination more than 20 years after the index surgery. The mean age at the time of surgery was 41 years, and a CT scan was performed at an average of 22.0 years postoperatively (range, 20.0 to 25.1). The CT scans were thoroughly assessed for osteolysis, stem notching, and ceramic component fracture. RESULTS: No loosening was observed in the acetabular cup or femoral stem. Stem notching was observed in 3 hips (2.8%). In the CT scan taken after a minimum of 20 years of follow-up, 1 case (0.9%) of osteolysis around the cup and 2 cases (1.9%) of osteolysis around the femoral stem were noted. Suspected chip fractures of the ceramic insert were discovered in 4 cases (3.7%). Despite these findings, the patients remained asymptomatic, and no subsequent surgical intervention was needed after close follow-up. CONCLUSIONS: Routine CT examinations for patients who underwent THA using CoC bearings over 20 years ago revealed unexpected findings, such as osteolysis and suspected chip fractures of the ceramic liner. However, routine CT scans may not be universally necessary. The CT evaluation in this cohort should be selectively performed for patients who have relevant clinical symptoms. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Maxillary Sinus Augmentation and Implant Installation in Patients With Pseudocysts and Mucous Retention Cysts.

This case study systematically assessed diverse approaches to sinus augmentation in the presence of sinus pathology. Three patients were carefully selected and categorized as pseudocyst (PsC) (type 1), mucous retention cyst (MRC) smaller than 20 mm (type 2), and MRC larger than 20 mm in size (type 3). All patients underwent sinus augmentation procedures, with each case utilizing a unique surgical approach. Spontaneous drainage was performed for the patient with PsC (type 1), followed by uncomplicated sinus augmentation. For the patient with an MRC smaller than 20 mm (type 2), aspiration of the cyst contents preceded sinus augmentation. Conversely, the patient with a larger MRC (type 3) underwent cyst enucleation followed by sinus augmentation after complete recovery of the sinus membrane. No complications were noted in any of the cases, and follow-up revealed stable implant installation at the site of sinus augmentation. Within the constraints of this study, the choice of surgical procedure, whether involving spontaneous drainage, aspiration, or enucleation, should be guided by an anticipated pathologic diagnosis and the size of the sinus cyst. This informed approach empowers clinicians to make well-informed decisions for the best possible outcomes and sustained results. Overall, this study offers valuable insights for clinicians seeking to optimize sinus augmentation procedures in the presence of sinus pathology.

Three-Dimensional Analysis of Bone Remodeling After Closed Treatment for Mandibular Condylar Head Fracture.

Closed treatment of mandibular condylar fractures has been used for its indications based on the fracture site, fracture status, and patient age. Posttreatment mandibular condyle size is associated with mandibular function; however, a few studies have reported bone remodeling patterns and volume changes in the condyle and glenoid fossa after mandibular condylar head fractures (CHFs). Therefore, volumetric changes in the mandibular condyle and glenoid fossa were analyzed in the present study, and bone remodeling patterns were evaluated after mandibular CHFs. The present study included 16 condyles from 12 patients who received closed treatment for CHF. After reconstruction of a 3-dimensional skull model, including the mandible, using computed tomography data taken immediately after injury and 6 months after treatment, volume changes in the mandibular condyle and glenoid fossa were analyzed. The condylar volume increased by 0.32±0.66 cm3 during the 6-month healing period without statistical significance (P=0.093). Regarding the glenoid fossa, the fossa showed a statistically significant volume increase of 0.41±0.59 cm3 (P=0.021), and 12 glenoid fossae (75%) showed downward bone apposition; however, no change or only mild bone resorption was observed in 4 glenoid fossae (25%). The results of this study indicated that the volume changes in the mandibular condyle after closed treatment of a mandibular CHF are not significant, and the glenoid fossa adapts to the displaced mandibular condyle through downward growth accompanied by volume increase.

Outcome and complication rate of total hip arthroplasty in patients younger than twenty years: which bearing surface should be used?

PURPOSE: Total hip arthroplasty (THA) in younger patients remains controversial due to concerns regarding long-term implant survival and potential complications. This study aimed to evaluate long-term clinical outcomes, complications, differences in complication and revision rates by bearing surfaces, and Kaplan-Meier survival curves for THA in patients under 20 years old. METHODS: A retrospective review was conducted for 65 patients (78 hips) who underwent THA between 1991 and 2018. Their mean age was 18.9 years. Their clinical outcomes were assessed using the Harris Hip Score (HHS). Radiological outcomes were evaluated based on the presence of loosening, osteolysis, and heterotopic ossification. Complications such as dislocation, periprosthetic fractures, and infections were assessed. The mean follow-up period was 13.2 years (range, 5.0-31.2 years). RESULTS: The mean HHS improved from 44.6 to 90.1. There were two cases of dislocation. However, no periprosthetic fracture, deep infection, or ceramic component fracture was noted. There were 19 revisions of implants. Eighteen of 19 hips were operated with hard-on-soft bearings in the index surgery (p < 0.01). The 23-year survivorship was 97.8% for THA using ceramic-on-ceramic bearings, while the 31-year survivorship was 36.7% using hard-on-soft bearings. CONCLUSION: THA in patients under 20 years old yielded promising clinical and radiological outcomes, although polyethylene-bearing-related concerns persisted. Previously operated patients with hard-on-soft bearing should be meticulously examined during the follow-up. As ceramic-on-ceramic bearing showed excellent survivorship in this particular cohort, we recommend the use of this articulation as the bearing of choice.

Ipsilateral pubic ramus fracture during total hip arthroplasty is not rare: does it matter?

INTRODUCTION: Periprosthetic fractures in total hip arthroplasty (THA) have been well described and studied. However, there is a lack of reports on ipsilateral pubic ramus fractures during THA due to the rare occurrence of such fractures and ambiguity of symptoms. With the use of postoperative computed tomography (CT) examinations, we have identified that asymptomatic ipsilateral pubic ramus fractures occur frequently during THA. This study aims to evaluate the incidence, location, clinical outcomes, and risk factors of ipsilateral pubic ramus fractures during THA. METHODS: From May 2022 to March 2023, a single surgeon performed 203 THAs in 183 patients at a single institution. All patients underwent postoperative CT scans three days after THA. The patients with ipsilateral pubic ramus fractures were followed up for a minimum of six months. Basic demographics, osteoporosis, general conditions of the operations, and outcomes of THA were investigated in all patients. RESULTS: Twenty-two cases (10.8%) of ipsilateral pubic ramus fractures were identified on postoperative CT scans. All fractures were located near the origin of the superior or inferior pubic ramus. Five fractures were detected on simple postoperative radiographs. The fractures did not cause any further complications at a minimum of six-month postoperative follow-up. Univariate and multivariate analyses did not identify any risk factors associated with these fractures. CONCLUSIONS: Although the incidence of ipsilateral pubic ramus fractures during THA is high, treatment is not required as they do not cause any significant clinical symptoms or affect the prognosis of THA. However, the possibility of occurrence of these fractures must be explained to the patients before surgery.

On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. METHODS: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. RESULTS: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. CONCLUSIONS: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.

Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination.

BACKGROUND: Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. METHODS: We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. RESULTS: We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell-matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. CONCLUSION: We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.

Resolution of Nonmass Enhancement Extension to the Nipple at Breast MRI after Neoadjuvant Chemotherapy: Pathologic Response and Feasibility for Nipple-sparing Mastectomy.

Background Nipple-sparing mastectomy (NSM) is usually contraindicated in patients with nonmass enhancement (NME) extension to the nipple at breast MRI. However, little is known about the feasibility of NSM when NME extension to the nipple resolves after neoadjuvant chemotherapy (NAC). Purpose To evaluate whether NSM is an appropriate surgical procedure for patients in whom NME extension to the nipple resolves after NAC. Materials and Methods This retrospective study included 383 women with NME at baseline MRI who underwent NAC followed by mastectomy between January 2007 and March 2022 at a single institution. NME extension to the nipple was assessed using breast MRI before NAC (hereafter, pre-NAC) and after NAC (hereafter, post-NAC). In 326 women who underwent mastectomy with removal of the nipple-areolar complex, the rate of pathologic analysis-confirmed tumor invasion of the nipple compared with NME extension to the nipple at post-NAC breast MRI was evaluated. Tumor involvement of the nipple was also assessed in those with complete pathologic response at posttreatment MRI. Furthermore, the outcomes in 57 women undergoing NSM were investigated, particularly in patients with NME extension to the nipple at initial diagnosis. Results Of the 326 women who underwent mastectomy with removal of the nipple-areolar complex (mean age, 49 years ± 9.4 [SD]), 217 patients (67%) showed NME extension to the nipple on pre-NAC MRI scans. Among the 153 women (70%) in whom the NME extension to the nipple resolved after NAC, the rate of pathologic analysis-confirmed tumor invasion of the nipple was 2.6% (four of 153 women; 95% CI: 0, 6.5). No pathologic analysis-confirmed tumor invasion of the nipple was detected in 31 women with complete response at MRI. Of the 57 women who underwent NSM, 12 (21%) with resolution of NME extension to the nipple after NAC had no relapse during the median follow-up of 31 months (range, 11-80 months). Conclusion Pathologic analysis-confirmed tumor invasion of the nipple was rare in women with resolution of nonmass enhancement extension to the nipple after neoadjuvant chemotherapy (NAC). Therefore, nipple-sparing mastectomy could be feasible in this population, especially in those with complete MRI response to NAC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 directly binds and stabilizes Nrf2 in breast cancer.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) has been frequently overexpressed in many types of malignancy, suggesting its oncogenic function. It recognizes phosphorylated serine or threonine (pSer/Thr) of a target protein and isomerizes the adjacent proline (Pro) residue, thereby altering folding, subcellular localization, stability, and function of target proteins. The oncogenic transcription factor, Nrf2 harbors the pSer/Thr-Pro motif. This prompted us to investigate whether Pin1 could bind to Nrf2 and influence its stability and function in the context of implications for breast cancer development and progression. The correlation between Pin1 and Nrf2 in the triple-negative breast cancer cells was validated by RNASeq analysis as well as immunofluorescence staining. Interaction between Pin1 and Nrf2 was assessed by co-immunoprecipitation and an in situ proximity ligation assay. We found that mRNA and protein levels of Pin1 were highly increased in the tumor tissues of triple-negative breast cancer patients and the human breast cancer cell line. Genetic or pharmacologic inhibition of Pin1 enhanced the ubiquitination and degradation of Nrf2. In contrast, the overexpression of Pin1 resulted in the accumulation of Nrf2 in the nucleus, without affecting its transcription. Notably, the phosphorylation of Nrf2 at serine 215, 408, and 577 is essential for its interaction with Pin1. We also identified phosphorylated Ser104 and Thr277 residues in Keap1, a negative regulator of Nrf2, for Pin1 binding. Pin1 plays a role in breast cancer progression through stabilization and constitutive activation of Nrf2 by competing with Keap1 for Nrf2 binding.

Granulicatella seriolae sp. nov., a Novel Facultative Anaerobe Isolated from Yellowtail Marine Fish.

A bacterial strain, designated as S8T, was isolated from the gut contents of Seriola quinqueradiata from the coastal sea area of Jeju Island, South Korea. The strain is a Gram-staining positive, non-motile, non-spore-forming, facultative anaerobic coccus. Optimal growth was observed at 30 °C, pH 8.0-9.0, and 0-0.5% w/v NaCl, under anaerobic conditions. The predominant fatty acids were C18:1 ω9c, C16:0, C18:0, and C16:1 ω9c, while quinone was not detected. The genome was 2,224,566 bp long, with a GC content of 38.2%. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain S8T had 96.2% similarity with Granulicatella adiacens ATCC 49175T, its closest known species according to nomenclature. The DNA-DNA hybridization (dDDH), average nucleotide identity, and average amino acid identity values between strain S8T and G. adiacens ATCC 49175T were 25.7%, 85.5%, and 77.2%, respectively, all of which fall below the recommended threshold for species differentiation. Based on genomic, phenotypic, and phylogenetic evidence, we propose that strain S8T should be a novel species within the genus Granulicatella, for with the name Granulicatella seriolae sp. nov. is proposed. The type strain is S8T (KCTC 43438T = JCM 35604T).

Minimal pre-operative leg length discrepancy as a risk factor of post-operative leg length discrepancy after total hip arthroplasty: a retrospective study of patients with non-traumatic osteonecrosis of the femoral head.

BACKGROUND: Leg length discrepancy (LLD) is one of the troublesome complications of total hip arthroplasty (THA). Previously, several risk factors have been suggested, but they were subjected to their inherent limitations. By controlling confounding variables, we hypothesized that known risk factors be re-evaluated and novel ones be discovered. This study aimed to analyze the independent risk factors for LLD after primary THA in patients with non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: We retrospectively reviewed patients with non-traumatic ONFH who underwent unilateral THA between 2014 and 2021. All patients were operated by one senior surgeon using a single implant. Demographic data, surgical parameters, and radiological findings (pre-operative LLD, Dorr classification, and femoral neck resection) were analyzed to identify the risk factors of ≥ 5 mm post-operative LLD based on radiological measurement and to calculate odds ratios by logistic regression analysis. Post hoc power analysis demonstrated that the number of analyzed patients was sufficient with 80% power. RESULTS: One hundred and eighty-six patients were analyzed, including 96 females, with a mean age of 58.8 years at the time of initial THA. The average post-operative LLD was 1.2 ± 2.9 mm in the control group and 9.7 ± 3.2 mm in the LLD group, respectively. The LLD group tended to have minimal pre-operative LLD than the control group (-3.2 ± 5.1 mm vs. -7.9 ± 5.8 mm p = 2.38 × 10- 8). No significant difference was found between the groups in age, gender, body mass index, femoral cortical index, and implant size. CONCLUSION: Mild pre-operative LLD is associated with an increased risk of post-operative LLD after primary THA in patients with ONFH. Thus, surgeons should recognize pre-operative LLD to achieve an optimal outcome and must inform patients about the risk of developing LLD.

Metastasis of Renal Cell Carcinoma to the Mandible.

Renal cell carcinoma (RCC) is the most common tumor of the kidney. Although RCC often metastasizes to other organs, metastasis to the head and neck region is rare, and metastasis to the mandible is very unusual. Given the fact that metastasis of primary neoplasms is not always predictable, it is essential to rule out metastatic carcinoma in jaw lesions. We herein report a rare presentation of metastasis of RCC to the mandible, in which the metastatic lesion in the oral cavity was found first, followed by the primary lesion, in a 22-year-old girl who suffered from pain in the left temporomandibular joint on mouth opening and hypoesthesia of the left chin, left lower lip, and left lower gum.

Effects of dietary piperine supplementation on innate immunity, growth performance, feed utilization and intestinal morphology of olive flounder (Paralichthys olivaceus).

Piperine, the main bioactive component of black pepper (Piper nigrum) or long pepper (Piper longum), has anti-inflammatory, antifungal, and antibacterial properties. This study was carried out to evaluate the supplemental effects of piperine in olive flounder (Paralichthys olivaceus) diets. Six isonitrogenous and isolipidic diets were formulated to contain different levels of piperine at 0.00, 0.25, 0.50, 0.75, 1.00, and 2.00 g/kg (Con, P25, P50, P75, P100, and P200, respectively). Diets were randomly allocated to triplicate groups of fish (initial weight 27.6 ± 0.4 g, 30 fish/tank) and fed three times daily for 8 weeks. Results showed that dietary piperine significantly improved fish growth and feed utilization efficiency. The highest growth, including the highest Igf-1 mRNA expression, was observed in the P50 group, while P50 and P75 groups showed the highest protein efficiency ratio. Compared to the Con group piperine supplemented groups had significantly higher lysozyme activity, immunoglobulin level, and phagocytosis activities. Plasma cholesterol was significantly lower in fish fed P200 diet. Dry matter and protein digestibility were higher in P25, P50, and P75 groups than in Con group. Dietary piperine increased the intestinal villi length and goblet cell counts. In the challenge test against Edwardsiella tarda, all the groups supplemented with piperine showed higher cumulative survival compared to Con group. Therefore, these findings indicate that dietary piperine supplementation can improve growth performance, innate immunity, disease resistance, diet digestibility, and intestinal morphology of olive flounder. The optimum dietary piperine level seems to be approximately 0.5 g/kg for the fish.

RT-induced dynamic changes in the lymphocyte-to-monocyte ratio in patients with breast cancer indicate poor prognosis.

PURPOSE: Radiation-induced anti-tumor responses occur in the immune system, particularly in peripheral blood mononuclear cells (PBMCs), which are overly sensitive to ionizing radiation. Irradiation of PBMCs is associated with inflammation. We assessed the association between radiotherapy (RT)-induced changes in peripheral blood cells, utilizing the lymphocyte-to-monocyte ratio (LMR), and survival outcome in breast cancer patients who underwent breast-conserving surgery followed by adjuvant RT. METHODS: LMR values were obtained from retrospective data, and serial sampling of blood before the first and last RT sessions was performed. The cut-off point was analyzed using the Youden index and receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were the main outcomes. RESULTS: Patients with RT-induced low LMR had significantly shorter RFS (hazard ratio [HR] 2.730; 95% confidence interval [CI], 1.607-4.636, P = 0.0002) and OS (HR 2.890; 95% CI 1.410-5.924, P = 0.0038). The results were more robust in the subgroup of patients who received chemotherapy. Multivariate analysis showed that lymph node metastasis and RT-induced low LMR were associated with poor RFS (HR 1.763; 95% CI, 1.017-3.059, P = 0.044) and OS (HR 2.254; 95% CI, 1.060-4.796, P = 0.035). CONCLUSION: This study demonstrates that RT-induced low LMR is a valid prognostic marker for recurrence and survival in breast cancer patients undergoing RT.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.